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1.
PLoS One ; 16(9): e0257520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543353

RESUMO

INTRODUCTION: Previous work had shown that machine learning models can predict inflammatory bowel disease (IBD)-related hospitalizations and outpatient corticosteroid use based on patient demographic and laboratory data in a cohort of United States Veterans. This study aimed to replicate this modeling framework in a nationally representative cohort. METHODS: A retrospective cohort design using Optum Electronic Health Records (EHR) were used to identify IBD patients, with at least 12 months of follow-up between 2007 and 2018. IBD flare was defined as an inpatient/emergency visit with a diagnosis of IBD or an outpatient corticosteroid prescription for IBD. Predictors included demographic and laboratory data. Logistic regression and random forest (RF) models were used to predict IBD flare within 6 months of each visit. A 70% training and 30% validation approach was used. RESULTS: A total of 95,878 patients across 780,559 visits were identified. Of these, 22,245 (23.2%) patients had at least one IBD flare. Patients were predominantly White (87.7%) and female (57.1%), with a mean age of 48.0 years. The logistic regression model had an area under the receiver operating curve (AuROC) of 0.66 (95% CI: 0.65-0.66), sensitivity of 0.69 (95% CI: 0.68-0.70), and specificity of 0.74 (95% CI: 0.73-0.74) in the validation cohort. The RF model had an AuROC of 0.80 (95% CI: 0.80-0.81), sensitivity of 0.74 (95% CI: 0.73-0.74), and specificity of 0.72 (95% CI: 0.72-0.72) in the validation cohort. Important predictors of IBD flare in the RF model were the number of previous flares, age, potassium, and white blood cell count. CONCLUSION: The machine learning modeling framework was replicated and results showed a similar predictive accuracy in a nationally representative cohort of IBD patients. This modeling framework could be embedded in routine practice as a tool to distinguish high-risk patients for disease activity.


Assuntos
Corticosteroides/uso terapêutico , Algoritmos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adulto , Área Sob a Curva , Feminino , Hospitalização , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Leucócitos/citologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
2.
Transl Vis Sci Technol ; 10(6): 20, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34111266

RESUMO

Purpose: To evaluate the feasibility of capturing and interpreting retinal images in a workplace environment using a multimodal, cloud-based, diabetic retinal screening program combined with electronic self-reported questionnaires. The burden of diabetic retinopathy (DR) and other retinal conditions, healthcare utilization, and visual function were also assessed. Methods: A cross-sectional feasibility study was conducted at the Genentech, Inc., Campus Health Center. Eyes of participants were imaged using ultra-widefield (UWF) color fundus photography (CFP) and spectral-domain optical coherence tomography (SD-OCT). A cloud-based platform was used for the automated, seamless transfer of images to a remote reading center for evaluation for DR and other retinal pathologies. Electronic surveys collected participants' self-reported medical histories, healthcare utilization, and visual function data. Results: Among 100 participants (mean age, 43.9 years; 44% male), 33% of them self-reported diabetes. Eye examinations within the past 12 months were reported by 71% of all participants (n = 71/100) and by 85% (n = 28/33) of those with self-reported diabetes. Among participants with complete screening images from both UWF-CFP and SD-OCT, 20% (n = 6/30) of those with self-reported diabetes and 8.5% (n = 5/59) of participants with no history of diabetes were unaware they had mild/moderate nonproliferative DR. Among all participants, 20% (20/100) had a retinal finding, on either UWF-CFP or SD-OCT, or both, which prompted a referral for further evaluation. Conclusions: A retinal screening program deployed via a secure, scalable, and interoperable cloud-based platform was feasible and conveniently integrated into the workplace. Translational Relevance: Cloud-based platforms could be used to promote a secure, scalable, and interoperable system for retinal screening in nontraditional environments.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Adulto , Computação em Nuvem , Estudos Transversais , Retinopatia Diabética/diagnóstico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Local de Trabalho
3.
Curr Med Res Opin ; 37(1): 1-8, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33206572

RESUMO

AIMS: Six prospective real-world studies of antihypertensive treatment with valsartan-centric regimens were pooled to: (1) examine the effectiveness of ∼90 days of second- or later-line valsartan treatment in hypertensive patients with known comorbidities; and (2) identify physician- and patient-related determinants associated with systolic (SBP) and diastolic blood pressure (DBP) outcomes in these patients. METHODS AND MATERIALS: A pooled analysis was performed of an evaluable sample of 11,999 hypertensive patients with known comorbidities treated ∼90 days with valsartan-centric regimens. We applied hierarchical linear and logistic regression models to identify determinants of blood pressure (BP) outcomes and a potential physician class effect. RESULTS: Valsartan regimens resulted in mean (SD) SBP and DBP reductions of 18.0 (15.8) mmHg and 9.5 (10.1) mmHg, respectively, at ∼90 days, yielding SBP, DBP and combined SBP/DBP control rates of 44.0%, 67.2% and 39.3%, respectively. About a quarter of the variance in 90 day BP values was attributable to a physician class effect. BP outcomes declined with physicians' increasing years in practice and being male. At the patient level, BP outcomes declined with SBP and DBP at diagnosis; diabetes; higher cholesterol and BMI; lower valsartan and hydrochlorothiazide (HCTZ) doses; and concomitant anti-hypertensives. Older age was associated with improved DBP. A proxy of physician vigilance, cardiovascular disease history, was associated with improved BP outcomes, as were patient adherence and higher doses of valsartan in combination with HCTZ. CONCLUSIONS: Valsartan-centric regimens have significant BP lowering benefits in this pooled sample of patients with known comorbidities. Many observed determinants of BP outcomes are modifiable or manageable.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão , Valsartana/uso terapêutico , Idoso , Pressão Sanguínea/fisiologia , Comorbidade , Diabetes Mellitus , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Estudos Prospectivos , Fatores de Risco
4.
J Allergy Clin Immunol ; 145(2): 528-536.e1, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31145939

RESUMO

BACKGROUND: The Observational Study of the Use and Safety of Xolair (omalizumab) during Pregnancy (EXPECT) pregnancy registry was a prospective observational study established in 2006 to evaluate perinatal outcomes in pregnant women exposed to omalizumab and their infants. OBJECTIVE: This analysis compares EXPECT outcomes with those from a disease-matched population of pregnant women not treated with omalizumab. Data from a substudy of platelet counts among newborns are also presented. METHODS: The EXPECT study enrolled 250 women with asthma exposed to omalizumab during pregnancy. The disease-matched external comparator cohort of women with moderate-to-severe asthma (n = 1153), termed the Quebec External Comparator Cohort (QECC), was created by using data from health care databases in Quebec, Canada. Outcome estimates were age adjusted based on the maternal age distribution of the EXPECT study. RESULTS: Among singleton infants in the EXPECT study, the prevalence of major congenital anomalies was 8.1%, which was similar to the 8.9% seen in the QECC. In the EXPECT study 99.1% of pregnancies resulted in live births, which was similar to 99.3% in the QECC. Premature birth was identified in 15.0% of EXPECT infants and 11.3% in the QECC. Small for gestational age was identified in 9.7% of EXPECT infants and 15.8% in the QECC. CONCLUSION: There was no evidence of an increased risk of major congenital anomalies among pregnant women exposed to omalizumab compared with a disease-matched unexposed cohort. Given the observational nature of this registry, however, an absence of increased risk with omalizumab cannot be definitively established.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Omalizumab/efeitos adversos , Resultado da Gravidez/epidemiologia , Adulto , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Sistema de Registros
5.
Clin Ther ; 42(1): 130-143.e3, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883702

RESUMO

PURPOSE: Therapeutic management of inflammatory bowel disease (IBD) is challenging, and available therapies are associated with adverse events (AEs) that may lead to treatment discontinuation. This study evaluated the rate of drug-related AEs of special interest (AESIs) associated with IBD therapies and compare health care costs among patients with IBD who did and did not experience AESIs. METHODS: A retrospective cohort analysis was conducted using claims data from a German Sickness Fund (Allgemeine Ortskrankenkasse PLUS). Patients were diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and newly initiating treatment with immunosuppressant, anti-tumor necrosis factor α, or anti-integrin therapies from January 1, 2011, to December 31, 2015. Patients were required to have continuous insurance coverage and no evidence of use of these IBD therapies for 12 months before the date of newly initiating therapy (index date). Rates of AESIs were based on 28 different events or chronic conditions associated with IBD treatment. Direct health care costs were reported separately for patients who did or did not experience AESIs. Only treatment periods lasting ≥60 days were considered. AESI rates related to all possible treatment patterns were calculated and reported as the number of events per 10,000 patient-years. Health care costs were calculated based on IBD-related health care resource use. FINDINGS: A total of 1126 (CD, n = 676; UC, n = 450) patients met the inclusion criteria. Mean age was 36.5 years for patients with CD and 42.5 years for patients with UC; 60.5% and 47.6% were female, respectively. Median observed time since the index date was 1460 and 1552 days, for patients with CD and UC. The overall rate for any AESI was 1392.4 and 1917.9 events per 10,000 patient-years in patients with CD and those with UC. Severe infections and diabetes mellitus were the most common AESIs. Significant differences in mean total direct health care costs were found for CD patients with AESIs versus those without (€8920.08 and €6004.86; P < 0.001). A similar trend was observed with mean drug costs and mean medical costs. In UC, total direct health care costs, although generally higher in patients with AESIs, were not significantly different; however, medical costs were (€1946.93 vs €971.28; P < 0.001). IMPLICATIONS: AEs are common in patients with IBD treated with current therapies and associated with substantial health care costs. An urgent need exists for development of IBD treatments that are associated with lower rates of AEs.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/economia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/economia , Imunossupressores/efeitos adversos , Imunossupressores/economia , Adulto , Estudos de Coortes , Custos de Medicamentos , Feminino , Alemanha , Custos de Cuidados de Saúde , Humanos , Integrinas/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
6.
Int J Risk Saf Med ; 30(2): 101-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31282430

RESUMO

This paper argues that health policies should transcend national boundaries yet should not reach the supranational level. Along with multinational global health efforts, such cross-national health policies are essential to leverage joint efforts by countries learning from their peers that experience similar health system challenges. In our analysis, we used World Bank Health, Nutrition, and Population (HNP) data from 1995 to 2014 for East Asia Pacific (EAP) countries to explore health system comparability across member nations. We applied a hierarchical cluster analysis using Ward's method and a squared Euclidean distance approach to classify 24 EAP countries into four relatively stable clusters based on their (dis)similarities over nine selected health expenditure and health system performance related indicators. One-way analysis of variance (ANOVA) was used to assess the discreteness of the formed clusters. Each cluster had unique characteristics based on the included indicators and health system performance of the member countries. We present transnational health policy recommendations for the EAP region based on both our use of robust methodology and the resulting comparative clusters.


Assuntos
Saúde Global/estatística & dados numéricos , Política de Saúde , Cooperação Internacional , Formulação de Políticas , Análise de Variância , Análise por Conglomerados , Comparação Transcultural , Ásia Oriental/epidemiologia , Pesquisa sobre Serviços de Saúde , Humanos
7.
Org Lett ; 19(18): 4892-4895, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28849658

RESUMO

A robust and scalable route to the taccalonolide skeleton starting from trans-androsterone is presented. The synthesis features a cyclic hydroboration carbonylation reaction, which effectively establishes the trans-hydrindane DE ring junction in a remarkable annulation reaction, as well as a Claisen rearrangement and a catalytic Ullmann-type cyclization. This work is part of a larger effort to uncover new clinical candidates from the taccalonolide class of anticancer agents through advances in chemical synthesis.


Assuntos
Lactonas/química , Androsterona , Ciclização , Estrutura Molecular , Estereoisomerismo
10.
J Manag Care Spec Pharm ; 22(6): 618-25, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27231790

RESUMO

BACKGROUND: In recent years, comparative effectiveness tools and methods have evolved to assist health care decision makers in identifying optimal therapies. In-person training programs on comparative effectiveness research may be helpful in understanding and applying this information. OBJECTIVE: To provide a follow-up assessment of the use of comparative effectiveness research (CER) in the pharmacy and therapeutics (P&T) committee decision-making process, using information collected from participants 1 year after attending a live continuing education program, in which participants were taught about CER designs and how to access available CER resources through the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care (EHC) Program. METHODS: A retrospective, cross-sectional questionnaire was developed and mailed to 2 groups of individuals: CER workshop attendees and interested nonattendees (expressing an interest in attending a workshop but did not attend for unknown reasons). The questionnaire asked respondents to indicate personal and organizational use of CER in the decision-making process. Participants were asked to indicate whether their knowledge, ability, and use of CER studies increased since participating in the program. Data were analyzed using nonparametric tests to compare the responses of attendees and nonattendees, as well as overall reliability of the instrument. RESULTS: A total of 164 respondents completed the questionnaire (63 attendees and 101 nonattendees; overall response rate = 44%). The majority of respondents were pharmacists (n = 157, 95.7%) and were affiliated with a hospital (n = 106, 64.6%). Proportions of attendees and nonattendees differed significantly in the use of EHC research reviews/reports (45% and 28%, respectively; P = 0.02) and EHC executive summaries of research reviews/reports (48% and 29%, respectively; P = 0.01). At 1-year follow-up, the majority of attendees reported an increase ("somewhat" or "very much") in knowledge of CER (91.5%), ability to use CER (83.0%), and use of CER studies (58.7%). CONCLUSIONS: Health professionals attending a continuing education CER program reported higher use of EHC CER materials compared with nonattendees. Additionally, attendees reported increased use of CER in clinical decision making. A continuing education program such as this may provide an effective avenue for introducing CER methods and resources to the P&T committee and clinical decision-making processes. DISCLOSURES: This project was supported by grant number R18HS019220 from the Agency of Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency of Healthcare Research and Quality. Augustine has stock in Pfizer. The authors declared no other potential conflicts of interest associated with this study. Study concept and design were primarily contributed by Malone, along with Warholak, Hines, Brown, Hurwitz, and Taylor. Warholak, Hines, Brown, Hurwitz, and Taylor collected the data, assisted by Malone, Brixner, Cobaugh, and Schlaifer. Data interpretation was performed by Malone and Augustine, with assistance from the other authors. The manuscript was written primarily by Augustine, with assistance from Malone, Sun, Warholak, Hines, Brown, Hurwitz, and Taylor. Malone revised the manuscript, assisted by Warholak, Hines, Brown, Hurwitz, Taylor, Brixner, Cobaugh, and Schlaifer.


Assuntos
Membro de Comitê , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Pessoal de Saúde/educação , Farmácia , Adulto , Idoso , Estudos de Coortes , Pesquisa Comparativa da Efetividade/tendências , Estudos Transversais , Educação/métodos , Educação/tendências , Feminino , Seguimentos , Pessoal de Saúde/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Farmacêuticos/tendências , Farmácia/métodos , Farmácia/tendências , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e Questionários
11.
Clin Ther ; 37(4): 842-57, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25704107

RESUMO

PURPOSE: The objectives of this study were to simulate for the European Union G5 countries the potential cost savings of converting patients from originator granulocyte colony-stimulating factor (G-CSF) filgrastim and pegfilgrastim to a biosimilar filgrastim, to evaluate how reallocating these savings could increase patient access to antineoplastic therapy, and to estimate the number of patients needed to convert to provide antineoplastic treatment to one patient. METHODS: Three models were built: (1) to estimate the costs of using originator G-CSFs and the savings generated from switching to a biosimilar G-CSF, (2) to estimate the incremental number of patients who could be provided antineoplastic therapy-rituximab or trastuzumab-in a hypothetical panel of 10,000 patients with cancer, and (3) to calculate the number of patients needed to convert to provide access to anticancer therapy. Scenarios were developed in which the rate of conversion was varied to estimate the effect on total cost savings. This study took the perspective of the payer in the European Union. FINDINGS: The savings associated with the biosimilar filgrastim over the originator filgrastim ranged from €785 (day 4) to €2747 (day 14) and increased with longer duration of therapy. By contrast, the savings associated with the biosimilar filgrastim over pegfilgrastim decreased over time, ranging from €6199 (day 4) to €471 (day 14). In a hypothetical panel of 10,000 patients with cancer, the savings associated with the biosimilar filgrastim over the originator filgrastim and the expanded access to antineoplastic therapy improved over time, irrespective of conversion rates. Conversely, in the same hypothetical panel, the savings associated with the biosimilar filgrastim over pegfilgrastim reduced over time, irrespective of conversion rates, along with the expanded access to antineoplastic treatment. Under conversion of the originator filgrastim to the biosimilar filgrastim, the number needed to convert to expand access to rituximab ranged from 4 to 14 patients, and the number needed to convert to expand access to trastuzumab ranged from 11 to 38 patients. Under conversion of pegfilgrastim to the biosimilar filgrastim, the number needed to convert to expand access to rituximab ranged from 2 to 24 patients, and the number needed to convert to expand access to trastuzumab ranged from 5 to 63 patients. IMPLICATIONS: Use of biosimilar G-CSFs for supportive cancer care could yield potential cost savings and improve patient access to antineoplastic therapy in a budget neutral way-a financial effect with an ethical perspective.


Assuntos
Medicamentos Biossimilares/administração & dosagem , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Filgrastim/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Medicamentos Biossimilares/economia , Redução de Custos/economia , União Europeia , Filgrastim/economia , Fator Estimulador de Colônias de Granulócitos/economia , Humanos , Neoplasias/tratamento farmacológico , Polietilenoglicóis , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/economia , Rituximab/uso terapêutico , Trastuzumab/uso terapêutico
12.
Br J Gen Pract ; 65(630): e9-15, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25548319

RESUMO

BACKGROUND: Patient adherence is often not monitored because existing methods of evaluating adherence are either burdensome or do not accurately predict treatment outcomes. AIM: To examine whether two simple, single-item physician-administered measures of patient adherence to antihypertensive medication are predictive of blood pressure outcomes. DESIGN AND SETTING: Retrospective database analysis of patients with hypertension treated in Belgian primary care. METHOD: Using pooled data from five observational studies, a sample was identified of 9725 patients who were assessed using two single-item physician-administered measures of adherence to antihypertensive medication: the first item of the Basel Assessment of Adherence Scale (BAAS) and the Visual Analogue Scale (VAS). These two assessment tools were administered by GPs during regular appointments with patients. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and combined SBP/DBP were measured at baseline and at 90 days. RESULTS: BAAS-identified adherent patients achieved lower mean SBP and DBP compared with non-adherent patients at 90 days (P<0.001), and had odds ratios of achieving blood pressure control of 0.66 (95% confidence intervals (CI) = 0.61 to 0.73, P<0.001) for SBP, 0.69 (95% CI = 0.62 to 0.76, P<0.001) for DBP, and 0.65 (95% CI = 0.59 to 0.72, P<0.001) for combined SBP/DBP. For VAS-identified adherent patients, the odds ratios of achieving blood pressure control were 0.93 (95% CI = 0.86 to 1.00, P<0.001) for SBP, 0.79 (95% CI = 0.73 to 0.85, P<0.001) for DBP, and 0.91 (95% CI = 0.84 to 0.99, P<0.001) for combined SBP/DBP. CONCLUSIONS: The first item of the BAAS and the VAS are independent predictors of blood pressure control. These methods can be integrated seamlessly into routine clinical practice by allowing GPs to quickly evaluate a patient's adherence and tailor treatment recommendations accordingly.


Assuntos
Anti-Hipertensivos/uso terapêutico , Efeitos Psicossociais da Doença , Hipertensão , Adesão à Medicação/estatística & dados numéricos , Atenção Primária à Saúde/métodos , Escala Visual Analógica , Idoso , Bélgica/epidemiologia , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos
13.
Acad Emerg Med ; 21(9): 1003-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25269581

RESUMO

OBJECTIVES: The objective of this study was to calculate national estimates of depression-related emergency department (ED) visits and associated health care resource use among children and adolescents 17 years or younger. Another goal was to explore the effects of certain sociodemographic and health care system factors and comorbidities on ED charges and subsequent hospitalization in the United States. METHODS: The authors analyzed data from the 2006 and 2009 National Emergency Department Sample (NEDS), the largest source of U.S. ED data. ED visits with all listed diagnoses (i.e., principal diagnosis plus secondary conditions) of depression were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 293.83, 296.2X, 296.3X, 300.4, and 311. Population-based estimates of ED visits, hospitalization, resource use, comorbidities, and demographics associated with pediatric depression were calculated. Potentially significant covariate associations were also explored using ED charges and hospital admission from the ED. RESULTS: The 2006 and 2009 NEDS sample contained 365,713 ED visits for pediatric depression; the majority were made by adolescents (87.9%). Of these, 27.2% were admitted to the hospital, 69.5% were treated and released, and <0.1% died in ED. The ED charges in 2012 U.S. dollars summed to a hospital bill of $443.8 million, with the ED plus inpatient charges ($1.2 billion) being more than double that amount. The median inpatient length of stay (LOS) was 4.0 days. Suicide and intentional self-inflicted injury were attempted by 31.4% of the patients. Attention-deficit, conduct, and disruptive disorders; anxiety disorders; substance use disorders; asthma; and infections were the most common comorbidities. In year 2009, a higher number of diagnoses, older age, being female, key comorbidities, and suicide and intentional self-inflicted injury were significantly associated with higher ED charges (all p < 0.05). Increased odds of hospital admission from the ED were significantly associated with a higher number of diagnoses, key comorbidities, and suicide and intentional self-inflicted injury (all p < 0.05). CONCLUSIONS: Pediatric depression is common in the ED and is associated with significant burden to the health care system. Certain factors such as a higher number of diagnoses, key comorbidities, and suicide and intentional self-inflicted injury are associated with increased health care costs and resource use. Special attention should be given to these factors, when present.


Assuntos
Depressão/epidemiologia , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Preços Hospitalares/estatística & dados numéricos , Hospitalização/economia , Adolescente , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Feminino , Humanos , Tempo de Internação/economia , Masculino , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
14.
Future Oncol ; 10(9): 1599-609, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25145430

RESUMO

AIM: We simulated the budget impact of biosimilar erythropoiesis-stimulating agent (ESA) in EU G5 countries. MATERIALS & METHODS: Three models were built to estimate the number of patients who could be provided with antineoplastic therapy with rituximab, bevacizumab or trastuzumab from cost savings of biosimilar erythropoietin use in a hypothetical panel of 100,000 patients. The associated number of patients needed to convert to biosimilar ESA to provide such treatments was also calculated. RESULTS: Under fixed dosing, the savings from 100% conversion were €110,592,159, translating into an additional 9770 rituximab, 3912 bevacizumab, or 3713 trastuzumab treatments. Under weight-based dosing, the savings from 100% conversion were €146,170,333, corresponding to an additional 12,913 rituximab, 5171 bevacizumab or 4908 trastuzumab treatments. The number of patients needed to convert ranged from four to 51. CONCLUSION: Using biosimilar ESA for supportive cancer care yields significant savings and increases accessibility to primary antineoplastic therapy in a budget neutral way.


Assuntos
Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Neoplasias/tratamento farmacológico , Anemia/induzido quimicamente , Anemia/economia , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Murinos/economia , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Bevacizumab , Medicamentos Biossimilares/uso terapêutico , Custos de Medicamentos , Epoetina alfa , Eritropoetina/economia , União Europeia , Hematínicos/economia , Humanos , Modelos Econômicos , Neoplasias/economia , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Rituximab , Trastuzumab
16.
Blood ; 123(12): 1927-37, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24497530

RESUMO

Mammals express thousands of long noncoding (lnc) RNAs, a few of which are known to function in tissue development. However, the entire repertoire of lncRNAs in most tissues and species is not defined. Indeed, most lncRNAs are not conserved, raising questions about function. We used RNA sequencing to identify 1109 polyadenylated lncRNAs expressed in erythroblasts, megakaryocytes, and megakaryocyte-erythroid precursors of mice, and 594 in erythroblasts of humans. More than half of these lncRNAs were unannotated, emphasizing the opportunity for new discovery through studies of specialized cell types. Analysis of the mouse erythro-megakaryocytic polyadenylated lncRNA transcriptome indicates that ~75% arise from promoters and 25% from enhancers, many of which are regulated by key transcription factors including GATA1 and TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatic species-specificity. RNA interference assays of 21 abundant erythroid-specific murine lncRNAs in primary mouse erythroid precursors identified 7 whose knockdown inhibited terminal erythroid maturation. At least 6 of these 7 functional lncRNAs have no detectable expression in human erythroblasts, suggesting that lack of conservation between mammalian species does not predict lack of function.


Assuntos
Eritropoese/genética , RNA Longo não Codificante/genética , Trombopoese/genética , Animais , Linhagem da Célula/genética , Sequência Conservada , Elementos Facilitadores Genéticos , Eritroblastos/metabolismo , Humanos , Células Progenitoras de Megacariócitos e Eritrócitos/metabolismo , Megacariócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Interferência de RNA , RNA Longo não Codificante/metabolismo , Especificidade da Espécie , Fatores de Transcrição/metabolismo
17.
Org Lett ; 16(3): 1012-5, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24446703

RESUMO

A conjugate-base-stabilized Brønsted acid facilitates catalytic enantioselective Pictet-Spengler reactions with unmodified tryptamine. The chiral carboxylic acid catalyst is readily assembled in just two steps and enables the formation of ß-carbolines with up to 92% ee. Achiral acid additives or in situ Boc-protection facilitate catalyst turnover.


Assuntos
Carbolinas/química , Ácidos Carboxílicos/química , Triptaminas/química , Catálise , Estrutura Molecular , Estereoisomerismo
19.
J Clin Hypertens (Greenwich) ; 15(9): 663-73, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24034660

RESUMO

The authors used pooled data from 6 valsartan-related studies including 3983 adherent and 10,663 nonadherent patients to evaluate blood pressure (BP) outcomes in both groups after 90 days of treatment, applying hierarchical linear and logistic regression to identify determinants of BP outcomes. The principal findings were that: (1) BP outcomes were consistently better in adherent patients; (2) approximately a quarter of the variance in 90-day BP values was attributable to a physician class effect; (3) common and unique patient- and physician-related variables were associated with BP outcomes in both groups; (4) physician vigilance was associated with better outcomes, especially in adherent patients; and (5) adherent patients were more likely to exhibit target organ damage and associated events while being prescribed more complex medication regimens. Adherence to antihypertensive medication may be a function of prior line treatment failure, severity of illness, and sequelae, and the ensuing patient resolution to change medication behavior.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Modelos Estatísticos , Cooperação do Paciente/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Idoso , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/fisiopatologia , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Autorrelato , Tetrazóis/farmacologia , Resultado do Tratamento , Valina/farmacologia , Valina/uso terapêutico , Valsartana
20.
J Manag Care Pharm ; 19(7): 549-57, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23964616

RESUMO

BACKGROUND: The topic of improving prescribing practices is a major focus of many national initiatives, not only to enhance the quality of health care but also to reduce medical care costs. Educational outreach (also known as academic detailing) is a type of postgraduate education where trained clinical consultants meet face-to-face with prescribers to provide one-on-one information. Ideally, such visits promote evidence-based knowledge, create trusting relationships, and induce practice change, particularly with regard to prescribing potentially interacting medications. OBJECTIVE: To evaluate the effect of an educational outreach program delivered by clinical pharmacists on reducing the rate of prescribing potential drug-drug interactions (DDIs). METHODS: The intervention was a prescriber-directed educational outreach program focused on 25 clinically important DDIs. The effect of the educational outreach was evaluated using a retrospective pre-post study design with a control group was conducted. A total of 19,606 prescribers were educated on the DDIs of interest. A control group of 19,606 prescribers, matched on prescribing volume and who did not receive the educational session were selected. Multivariate regression models were used to assess the impact of the educational program on the rate of prescribing potential DDIs. RESULTS: The 2 groups were significantly different with respect to age, profession, specialty, and geographic region. At baseline, mean DDI rates per 100 drug prescriptions were 0.8 and 0.7 for prescribers who received the educational session and those who did not, respectively. Following delivery of the educational outreach program, mean potential DDI rates increased to 1.46 and 1.53 per 100 precipitant drug prescriptions, an increase of 13.9% and 9.15% for the intervention and control groups, respectively. CONCLUSION: The current study was not able to demonstrate a significant beneficial effect of the educational outreach program on reducing the rate of prescribing potential DDIs.


Assuntos
Interações Medicamentosas , Prescrições de Medicamentos , Educação Médica Continuada , Educação em Saúde , Padrões de Prática Médica , Medicamentos sob Prescrição/administração & dosagem , Humanos , Pessoa de Meia-Idade , Farmacêuticos , Estudos Retrospectivos
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