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PURPOSE: Statins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. METHODS: A cross-sectional survey was conducted (2015-2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated. RESULTS: Muscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17-74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40-90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43-72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52-83%). CONCLUSIONS: The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible.
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Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Doenças Musculares/diagnóstico , Doenças Musculares/terapia , Padrões de Prática Médica , Colômbia/epidemiologia , Estudos Transversais , Relação Dose-Resposta a Droga , Substituição de Medicamentos , Europa (Continente)/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/epidemiologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/epidemiologia , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco , Arábia Saudita/epidemiologia , Emirados Árabes Unidos/epidemiologiaRESUMO
The transport characteristics of graphene devices with low n- or p-type carrier density (â¼10(10) -10(11) cm(-2) ), fabricated using a new process that results in minimal organic surface residues, are reported. The p-type molecular doping responsible for the low carrier densities is initiated by aqua regia. The resulting devices exhibit highly developed ν = 2 quantized Hall resistance plateaus at magnetic field strengths of less than 4 T.
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This paper presents a study of the quantum corrections caused by electron-electron interactions and localization to the conductivity in few-layer epitaxial graphene, in which the carriers responsible for transport are massive. The results demonstrate that the diffusive model, which can generally provide good insights into the magnetotransport of two-dimensional systems in conventional semiconductor structures, is applicable to few-layer epitaxial graphene when the unique properties of graphene on the substrate, such as intervalley scattering, are taken into account. It is suggested that magnetic-field-dependent electron-electron interactions and Kondo physics are required for obtaining a thorough understanding of magnetotransport in few-layer epitaxial graphene.
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Aim: To assess the cost-effectiveness of brentuximab vedotin (BV) versus physician's choice (methotrexate or bexarotene) for treating advanced cutaneous T-cell lymphoma. Materials & methods: A partitioned-survival model was developed from the National Health Service perspective in England and Wales. Model inputs were informed by the ALCANZA trial, real-world UK data, published literature or clinical experts. Results: Over the modeled lifetime, BV dominated physician's choice and provided an additional 1.58 life-years and 1.09 higher quality-adjusted life years with a net cost saving of £119,565. The net monetary benefit was £152,326 using a willingness-to-pay threshold of £30,000/quality-adjusted life year. Results were robust in sensitivity and scenario analyses. Conclusion: BV is a highly cost-effective treatment for advanced cutaneous T-cell lymphoma.
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Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Brentuximab Vedotin/uso terapêutico , Análise Custo-Benefício , Humanos , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/tratamento farmacológico , Medicina EstatalRESUMO
BACKGROUND: Comprehensive patient assessment and planning are central to esthetic treatment with injectables. MD ASA™ (Multi-Dimensional Aesthetic Scan Assessment) is a novel tool developed for this purpose. AIMS: To describe the MD ASA technique and present its preliminary application. METHODS: MD ASA breaks down the face into five hierarchies (H1-H5). H1 shifts patients' focus from "distractions" (individual lines and folds) toward the overall messages their face portrays, based on eight Emotional Attributes: four negative (tired, sad, angry, and saggy); four positive (youthful, attractive, contoured, and feminine/masculine). Three priority Emotional Attributes are selected for each patient. This is followed by a process of narrowing down through facial thirds (H2), periorbital and perioral dynamics (H3), facial units (H4), and subunits (H5), to arrive at a final assessment. Based on the key facial signs identified, this can be translated into MD Codes equations and thus a treatment formula. A retrospective analysis was performed based on 12 female patients injected by expert clinicians at an educational event. All patients were selected for, and treated using, a single MD Codes formula derived from a common MD ASA work-up. RESULTS: There were substantial differences between patients and clinicians in their views of which anatomical areas needed treatment-but good alignment on priority Emotional Attributes. Patients were treated only for three negative Emotional Attributes, but improvements were observed across all eight attributes. CONCLUSIONS: MD ASA provides a practical method for translating facial messages into actionable injectable treatment plans and facilitates greater patient-clinician alignment. Prospective studies are warranted.
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Técnicas Cosméticas , Estética , Feminino , Humanos , Estudos Prospectivos , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
BACKGROUND: Intralesional injection of low-dose 5-fluorouracil (5-FU) has recently been used as an experimental modality for treating keloid scarring and has shown promising efficacy in improving scar appearance and preventing recurrence of the keloid. OBJECTIVES: We sought to explore the cellular- and molecular-based evidence for the observed clinical benefits. METHODS: Primary cell lines of keloid fibroblasts were treated with 5-FU at a range of lower doses (â¼10 mg mL(-1) ) in monolayer culture and subjected to examination for cell viability, proliferative potential, apoptosis, cell cycle and associated proteins involved in cell cycle control. RESULTS: 5-FU significantly inhibited cell proliferation of keloid fibroblasts in the full dose range used in this study. The DNA synthesis was completely inhibited by 5-FU at 72 h, and significant cell apoptosis was observed at concentrations ≥ 1 mg mL(-1) for a period over 72 h. 5-FU caused a significant delay in cell cycle progression and the G2/M phase arrest. 5-FU induced p53 and p21 accumulation together with a decrease in cyclin B1 and Bcl-2 levels in treated keloid fibroblasts. CONCLUSIONS: Our data indicate that low-dose 5-FU (as low as 1 mg mL(-1) ) induces significant inhibition of proliferation, G2/M cell cycle arrest and apoptosis but not immediate cell death of keloid fibroblasts. The lack of tissue necrosis is a particular benefit as further scarring is likely to be prevented. These results support the use of low-dose 5-FU as a potential modality for treating keloid scars.
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Ciclo Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fluoruracila/farmacologia , Fase G2 , Imunossupressores/farmacologia , Queloide/tratamento farmacológico , Adolescente , Adulto , Apoptose/efeitos dos fármacos , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Criança , Ensaio de Imunoadsorção Enzimática , Fase G2/fisiologia , Humanos , Injeções Intralesionais , Queloide/metabolismo , Queloide/patologia , Adulto JovemRESUMO
AIMS: Utility values inform estimates of the cost-effectiveness of treatment for cardiovascular disease (CVD), but values can vary depending on the method used. The aim of this systematic literature review (SLR) was to explore how methods of elicitation impact utility values for CVD. MATERIALS AND METHODS: This review identified English-language articles in Embase, MEDLINE, and the gray literature published between September 1992 and August 2015 using keywords for "utilities" and "stroke", "heart failure", "myocardial infarction", or "angina". Variability in utility values based on the method of elicitation, tariff, or type of respondent was then reported. RESULTS: This review screened 4,341 citations; 290 of these articles qualified for inclusion in the SLR because they reported utility values for one or more of the cardiovascular conditions of interest listed above. Of these 290, the 41 articles that provided head-to-head comparisons of utility methods for CVD were reviewed. In this sub-set, it was found that methodological differences contributed to variation in utility values. Direct methods often yielded higher scores than did indirect methods. Within direct methods, there were no clear trends in head-to-head studies (standard gamble [SG] vs time trade-off); but general population respondents often provided lower scores than did patients with the disease when evaluating the same health states with SG methods. When comparing indirect methods, the EQ-5D typically yielded higher values than the SF-6D, but also showed more sensitivity to differences in health states. CONCLUSIONS: When selecting CVD utility values for an economic model, consideration of the utility elicitation method is important, as this review demonstrates that methodology of choice impacts utility values in CVD.
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Doenças Cardiovasculares/economia , Doenças Cardiovasculares/terapia , Análise Custo-Benefício , Recursos em Saúde/estatística & dados numéricos , Angina Pectoris/diagnóstico , Angina Pectoris/economia , Angina Pectoris/terapia , Doenças Cardiovasculares/diagnóstico , Feminino , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Indicadores Básicos de Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Modelos Econômicos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/economia , Infarto do Miocárdio/terapia , Estados UnidosRESUMO
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction. METHODS AND RESULTS: We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL-C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (-74.1%; 95% credible interval -79.81% to -68.58%), alirocumab 75 mg (-20.03%; 95% credible interval -27.32% to -12.96%), and alirocumab 150 mg (-13.63%; 95% credible interval -22.43% to -5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe. CONCLUSIONS: PCSK9 inhibitors added to medium- to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction. The network meta-analysis showed a significant treatment difference in LDL-C reduction for evolocumab versus alirocumab.
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Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Inibidores de PCSK9 , Inibidores de Serina Proteinase/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Regulação para Baixo , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/imunologia , Pró-Proteína Convertase 9/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Inibidores de Serina Proteinase/efeitos adversos , Resultado do TratamentoRESUMO
We report on magneto-transport measurements on low-density, large-area monolayer epitaxial graphene devices grown on SiC. We observe temperature (T)-independent crossing points in the longitudinal resistivity ρxx, which are signatures of the insulator-quantum Hall (I-QH) transition, in all three devices. Upon converting the raw data into longitudinal and Hall conductivities σxx and σxy, in the most disordered device, we observed T-driven flow diagram approximated by the semi-circle law as well as the T-independent point in σxy near e2/h. We discuss our experimental results in the context of the evolution of the zero-energy Landau level at low magnetic fields B. We also compare the observed strongly insulating behaviour with metallic behaviour and the absence of the I-QH transition in graphene on SiO2 prepared by mechanical exfoliation.
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OBJECTIVES: Our primary objective was to describe the prevalence of osteoporosis (OP) diagnosis in nursing home residents (NHRs). Secondary objectives included assessment of pharmacologic therapies and risk of fracture in NHRs with OP, as well as differentiating clinical characteristics of treated versus untreated male and female NHR with OP. Finally, we sought to evaluate persistence and compliance rates in NHRs treated with OP and determine the prevalence of severe renal impairment in NHRs with OP treated with a bisphosphonate. DESIGN: Retrospective cohort analysis. SETTING: US NH. PARTICIPANTS: NHRs with a Minimum Data Set (MDS) 3.0 record in the Omnicare Senior Health Outcomes (OSHO) data repository during the time period of October 1, 2011, to September 30, 2012. MEASUREMENTS: A patient was considered to have an OP diagnosis if MDS item I3800 indicated the NHR had OP or if the MDS record contained ICD-9-CM codes 733.0x. An expanded definition of OP diagnosis was explored, in which an NHR with a previous fracture (MDS items I3900, I4000, J1700C=1) was also considered to have OP. OP pharmacologic therapies were extracted from the pharmacy claims data and included alendronate, calcitonin salmon, denosumab, ibandronate, raloxifene, risedronate, and teriparatide. Using MDS items, cognitive impairment (Brief Instrument for Mental Status, Cognitive Performance Scale) and functional impairment (composite activities of daily living) were assessed. Using MDS and prescription claims data, high risk of fracture (at least 2 of the following: age ≥75 years, female gender, previous fracture, history of falls, and use of a bisphosphonate) was assessed. Persistence was indicated by continuous use of therapy without a gap of more than 60 days, compliance was calculated using the medication possession ratio, and creatinine clearance (Clcr) was calculated using a modified Cockcroft-Gault equation. RESULTS: The prevalence of OP in NHRs was 13.5%. Using the expanded OP definition, the prevalence of OP increased to 24.2%. Among NHRs with OP (n = 23,666), the mean age was 82.5 and 85.1% were female; 36.8% had gastroesophageal reflux disease or ulcer. Per the definition of high risk for fracture based on older age, female gender, prior fracture, fall history, and use of bisphosphonates, 89.0% of NHRs with OP met the criteria. Additionally, 10.8% had hip fracture, and 15.8% had other fracture. Overall, few NHRs with OP received active treatment: one-third received pharmacologic therapy, of which 73.5% received an oral bisphosphonate. Those with a history of hip fracture had similar treatment rates (31.7%) to those without (32.0%) (P = .804), whereas those with a history of other fracture were more likely to be treated (35.9%) than those without (31.2%) (P = .001). Two-thirds of residents with OP had moderate/severe cognitive impairment, and these residents were less likely to receive OP therapy than those without (P = .001). Persistence with pharmacologic therapy in NHR with a full year of pharmacy data (n = 1399) was higher for raloxifene (82.9%), with calcitonin salmon and bisphosphonates being similar, and the few NHRs who received teriparatide and denosumab were lower. Of the NHRs who received bisphosphonates for whom there was creatinine clearance data, 57% had a Clcr lower than 35 mL/min. CONCLUSION: The recognized prevalence of OP in NHRs using MDS records was low, but consistent with previous reports. Among those with a documented diagnosis of OP, approximately 89% of NHRs with OP were at high risk of fracture and only one-third were treated with active pharmacologic therapy. For those treated, persistence and compliance was suboptimal, but higher with oral therapies. More than half of NHRs with OP treated with bisphosphonates had Clcr of less than 35 mL/min, suggesting alternative forms of therapy should be considered. For all of these reasons, the opportunity exists to improve the care and medication use of residents with OP who are at high risk of fracture.
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Conservadores da Densidade Óssea/uso terapêutico , Instituição de Longa Permanência para Idosos , Casas de Saúde , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Absorciometria de Fóton/métodos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Conservadores da Densidade Óssea/farmacologia , Estudos de Coortes , Feminino , Avaliação Geriátrica , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Fraturas por Osteoporose/diagnóstico por imagem , Prevalência , Prognóstico , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não ParamétricasRESUMO
BACKGROUND: Prior research has shown that rates of persistence and compliance with osteoporosis therapies are associated with significantly fewer vertebral, nonvertebral, and hip fractures. A number of studies have examined medication-taking behavior with oral bisphosphonates and teriparatide, and these 1-year persistence rates have ranged from 39.9% to 56.7%. Limited real-world data are available regarding persistence and compliance rates with newer therapies such as denosumab, a RANK ligand inhibitor administered every 6 months as a subcutaneous injection. OBJECTIVE: To assess persistence and compliance rates over 1 year with newly initiated osteoporosis therapies, including denosumab, alendronate, ibandronate, risedronate, raloxifene, and teriparatide, within a cohort of commercially insured women. METHODS: Health insurance claims data derived from Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases (2010-2013) were used to conduct this retrospective cohort study. Adult females aged 18 years and older newly initiated on denosumab, raloxifene, teriparatide, or oral bisphosphonates (alendronate, ibandronate, or risedronate) between January 1, 2012, and March 31, 2012, were identified for inclusion. The date of the first qualifying osteoporosis prescription claim was defined as the index date. Patients were required to have at least 24 months of pre-index and at least 12 months of post-index continuous enrollment with medical and pharmacy benefits. Outcomes of patients initiating zoledronic acid (administered intravenously once yearly) were not assessed because a 12-month follow-up period would be insufficient for tracking persistence and compliance for this medication. Patients with Paget's disease of the bone, osteogenesis imperfecta, hypercalcemia, malignant cancer and metastasis, human immunodeficiency virus, and patients receiving preventive treatment for risk of breast cancer or denosumab in the pre-index period were excluded from the study. A subcohort of women aged 50 years and older at high risk for fracture (indicated by 1 or more of the following: aged ≥ 70 years, a pre-index fracture, or pre-index use of osteoporosis therapy that was discontinued at least 3 months prior to index) was analyzed separately. Propensity score weighting was used to adjust for differences in baseline demographic and clinical characteristics. Persistence, indicated by continuous use of the index therapy without a gap of 60 days or more; medication coverage ratio (MCR), the proportion of days covered by the index therapy; and compliance, defined as an MCR ≥ 0.80, were assessed during the 12-month follow-up. Logistic regression was used to estimate the odds of persistence and compliance for the treatment groups of interest. RESULTS: 10,863 female patients newly initiating osteoporosis medications (mean [SD] age: 66.2 [11.5] years) were identified. In the pre-index period, 35.8% of patients had a diagnosis of osteoporosis, while 11.5% had a diagnosis of osteopenia. Pre-index osteoporosis treatment was identified in 29.1% of patients, and 13.6% had an osteoporosis-related fracture in the pre-index period. Propensity score weight-adjusted 12-month persistence with the index medication varied from 28.9% to 35.1% for oral bisphosphonate users, 42.0% for raloxifene users, 59.1% for teriparatide users, and 68.3% for denosumab users (P less than 0.0001). The adjusted mean [SD] MCR was highest among patients treated with denosumab (0.83 [0.21]), followed by teriparatide (0.67 [0.31]), raloxifene, (0.57 [0.34]), ibandronate (0.54 [0.32]), alendronate (0.51 [0.33]), and risedronate (0.46 [0.33]; P less than 0.0001). The odds of being persistent and compliant across treatments favored denosumab (OR = 1.59 to 5.56, P less than 0.05 for persistence; OR = 2.44 to 7.69, P less than 0.0001 for compliance). Results were similar in the subcohort of women aged 50 years and older at high risk for fracture (n = 6,187; mean [SD] age: 71.9 [10.9] years). The odds of being persistent and compliant across treatments also favored denosumab (OR = 1.62 to 5.75, P less than 0.0001 for persistence; OR = 2.36 to 7.25, P less than 0.0001 for compliance). CONCLUSIONS: In a U.S. setting, rates of persistence and compliance over 12 months were higher among women initiating denosumab compared with those initiating other osteoporosis therapies.
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Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Adesão à Medicação , Osteoporose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Coortes , Difosfonatos/uso terapêutico , Feminino , Fraturas Ósseas/prevenção & controle , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Osteoporose/complicações , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Contemporary estimates of the prevalence of diagnosed osteoporosis among long-term care facility residents are limited. METHODS: This chart review collected data between April 1, 2012 and August 31, 2013 for adult (age ≥ 30 years) residents of 11 long-term care facilities affiliated with the Louisiana State University Health Sciences Center in the New Orleans metropolitan area. Data (demographics; comorbidities; osteoporosis diagnosis, risk factors, diagnostic assessments, treatments; fracture history; fall risk; activities of daily living) were summarized. Data for residents with and without diagnosed osteoporosis were compared using χ tests and t tests. RESULTS: The study included 746 residents (69% women, mean [SD] age: 76.3 [13.9] years, median length of stay approximately 18.5 months). An osteoporosis diagnosis was recorded for 132 residents (18%), 30% of whom received a pharmacologic osteoporosis therapy. Fewer than 2% of residents had bone mineral density assessments; 10% had previous fracture. Calcium and vitamin D use was more prevalent in residents with diagnosed osteoporosis compared with other residents (calcium: 49% versus 12%, vitamin D: 52% versus 28%; both P < 0.001). Over half (304/545) of assessed residents had a high fall risk. Activities of daily living were similarly limited regardless of osteoporosis status. CONCLUSIONS: The prevalence of diagnosed osteoporosis was higher than previously reported for long-term care residents, but lower than epidemiologic estimates of osteoporosis prevalence for the noninstitutional U.S. POPULATION: In our sample, osteoporosis diagnostic testing was rare and treatment rates were low. Our results suggest that osteoporosis may be underdiagnosed and undertreated in long-term care settings.
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Conservadores da Densidade Óssea/uso terapêutico , Fraturas Ósseas , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Osteoporose , Absorciometria de Fóton/métodos , Atividades Cotidianas , Idoso , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Avaliação Geriátrica/métodos , Humanos , Assistência de Longa Duração/métodos , Assistência de Longa Duração/estatística & dados numéricos , Masculino , Nova Orleans/epidemiologia , Osteoporose/complicações , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Three nasopharyngeal carcinoma (NPC) cell lines (CNE-1, CNE-2 and NPC/HK-1), two squamous cell carcinoma (SCC) cell lines (T2/CUHK and PWH-S1) and six head and neck cancer specimens (NPC [n = 4], SCC tongue [n = 1] and a thyroid cancer [n = 1]) were incubated with interferon (IFN)-alpha (5 x 10(4) iu/mL) and/or 13-cis retinoic acid (13RA; 10(-5) mol/L) for two days at 37 degrees C. In vitro chemosensitivity was measured using MTT assay. Mild growth inhibition of the five cell lines by IFN-alpha ranged from 7.1% to 51.8% (mean: 18.5%), whereas with 13RA it was zero to 19.7% (mean: 7%). Greater inhibition (14.8-51.0%, mean: 31.8%) was achieved when the two drugs were used in combination. Growth inhibition of the six surgical specimens ranged from 6.9% to 21% (mean: 13.6%) with IFN-alpha; zero to 10.3% (mean: 6.0%) with 13RA; and 6.6-26.5% (mean: 17.7%) when the two agents were combined. Four of the 11 samples showed synergistic antitumour effect when IFN-alpha and 13RA were combined, and six showed subadditive effect. The results show that IFN-alpha and 13RA have a mild in vitro antitumour effect on head and neck cancer cells, and the drug synergistic effect demonstrated in this study suggests that the two agents should be used in combination in clinical application.
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Antineoplásicos/farmacologia , Neoplasias de Cabeça e Pescoço/patologia , Interferon Tipo I/farmacologia , Isotretinoína/farmacologia , Divisão Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Proteínas Recombinantes , Células Tumorais CultivadasRESUMO
The development of graphene electronic devices produced by industry relies on efficient control of heat transfer from the graphene sheet to its environment. In nanoscale devices, heat is one of the major obstacles to the operation of such devices at high frequencies. Here we have studied the transport of hot carriers in epitaxial graphene sheets on 6H-SiC (0001) substrates with and without hydrogen intercalation by driving the device into the non-equilibrium regime. Interestingly, we have demonstrated that the energy relaxation time of the device without hydrogen intercalation is two orders of magnitude shorter than that with hydrogen intercalation, suggesting application of epitaxial graphene in high-frequency devices which require outstanding heat exchange with an outside cooling source.
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We have performed magnetotransport measurements on multilayer epitaxial graphene. By increasing the driving current I through our graphene devices while keeping the bath temperature fixed, we are able to study Dirac fermion heating and current scaling in such devices. Using zero-field resistivity as a self thermometer, we are able to determine the effective Dirac fermion temperature (TDF) at various driving currents. At zero field, it is found that TDF â I≈1/2. Such results are consistent with electron heating in conventional two-dimensional systems in the plateau-plateau transition regime. With increasing magnetic field B, we observe an I-independent point in the measured longitudinal resistivity ρxx which is equivalent to the direct insulator-quantum Hall (I-QH) transition characterized by a temperature-independent point in ρxx. Together with recent experimental evidence for direct I-QH transition, our new data suggest that such a transition is a universal effect in graphene, albeit further studies are required to obtain a thorough understanding of such an effect.
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OBJECTIVE: To evaluate the impact of Medicare Part D on medication utilization, drug expenditures, and medical expenditures in patients with arthritis. METHODS: This was a retrospective study using a national sample of 2,484 Medicare-eligible beneficiaries with arthritis from the pooled Medical Expenditure Panel Survey 2005-2008 data. Quantile regression was used to estimate the following outcomes: 1) number of prescription fills, 2) total drug expenditures, 3) out-of-pocket (OOP) drug expenditures, 4) Medicare-paid drug expenditures, 5) total medical expenditures (including all payments for inpatient/outpatient care, prescription drugs, and other medical services), 6) OOP medical expenditures, and 7) Medicare-paid medical expenditures. For each outcome variable, the 50th, 75th, and 90th percentiles were estimated, adjusting for demographics and comorbidity. All expenditures were inflation adjusted to 2008 dollars. RESULTS: From 2005 to 2008, the adjusted median annual number of prescription fills increased by 4.2 (14.6% change), from 28.4 to 32.6. The adjusted median OOP drug expenditures and OOP medical expenditures decreased by $151 (25.2% change) and $197 (17.3% change), respectively. The adjusted median Medicare-paid drug and medical expenditures increased by $366 and $896 (39.5% change), respectively. The adjusted total prescription expenditures increased by $845 (25.3% change) at the 75th percentile and by $1,194 (22.0% change) at the 90th percentile. The adjusted total medical expenditures did not change significantly. CONCLUSION: Medicare Part D resulted in increased medication utilization and significant reductions in OOP drug and OOP medical expenditures among beneficiaries with arthritis 3 years after its implementation. Part D was not associated with significant differences in total medical spending.
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Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite/tratamento farmacológico , Artrite/economia , Custos de Medicamentos , Gastos em Saúde , Medicare Part D/economia , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/economia , Redução de Custos , Prescrições de Medicamentos/economia , Feminino , Financiamento Pessoal , Custos Hospitalares , Hospitalização/economia , Humanos , Análise dos Mínimos Quadrados , Masculino , Estudos Retrospectivos , Fatores de Tempo , Estados UnidosAssuntos
Anti-Infecciosos Locais/uso terapêutico , Clorexidina/análogos & derivados , Nitrato de Prata/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Unidades de Queimados , Clorexidina/uso terapêutico , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , PrevalênciaRESUMO
BACKGROUND: Patients newly diagnosed with type 2 diabetes mellitus generally initiate therapy with either metformin [Met] or a sulfonylurea [SU] drug, followed by the addition of a second agent (Met, an SU drug, or a thiazolidinedione [TZD] drug) if the diabetes is not well controlled. If necessary, the usual third line of treatment is the addition of insulin. OBJECTIVE: The purpose of our study was to compare the progression to insulin among 3 cohorts receiving the oral antidiabetic (OAD) drug combinations Met/SU, Met/TZD, or SU/TZD. METHODS: This study used data from the Texas Medicaid database. The date of addition of a second OAD was considered a patient's index date and patients were followed for up to 5 years. Cox proportional hazards regression compared the progression to first insulin use among cohorts, using the Met/SU cohort as the reference group, while adjusting for demographics, comorbidities, and propensity scores. RESULTS: A total of 4083 patients were included in the study (Met/SU = 2872, Met/TZD = 438, and SU/TZD = 773). Insulin was added to the medication regimen of patients by the end of follow-up in 19.7% of the Met/SU cohort, 17.6% of the Met/TZD cohort, and 26.3% of the SU/TZD cohort. The adjusted Cox proportional model estimated that patients in the SU/TZD cohort had a 40% higher probability of progression to insulin than patients in the Met/SU cohort (odds ratio [OR] = 1.40; 95% CI, 1.19-1.64), whereas there was no significant difference between the Met/TZD and Met/SU cohorts (OR = 0.85; 95% CI, 0.67-1.08). CONCLUSIONS: It appears that mechanism of action may play a role in progression to insulin for concomitant OAD agents. A slower progression to insulin was seen for patients receiving a paired sensitizer regimen (ie, Met/TZD) compared with those receiving a secretagogue sensitizer regimen (ie, SU/TZD).
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Medicaid , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Bases de Dados como Assunto , Progressão da Doença , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Texas , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Sensory neurotisation of a muscle (sensory nerve transfer to the motor nerve of a muscle) produces muscle sensibility, but not skin sensibility. How to achieve sensation of a musculocutaneous flap remains a challenge to reconstructive microsurgeons. The purpose of our study was to determine if multiple nerve grafts which were placed vertically between the neuromuscular entrance zone of a muscle and a target area of dermis on the overlying skin could improve sensation. Thirty-six gracilis musculocutaneous flaps (18 rabbits) were raised and divided into three groups: group 1 consisted of 12 sensory neurotised gracilis musculocutaneous flaps with five nerve grafts each; group 2 consisted of another 12 sensory neurotised gracilis flaps with 10 nerve grafts each; and the control group consisted of 12 sensory neurotised gracilis musculocutaneous flaps without any nerve grafts. All nerve grafts spanned the distance between the neuromuscular entrance zone of the gracilis muscle and a specified 3 cm diameter area of the skin island. The saphenous nerve (sensory) was coapted to the obturator nerve (motor nerve of the gracilis) in an effort to achieve improved sensation of the skin island in the musculocutaneous flaps. After 6 months, the flaps were individually evaluated using cortical somatosensory evoked potentials (CSSEP) using normal, painful, cold and hot stimuli. One unoperated rabbit was studied as the baseline CSEEP for comparison. Retrograde horseradish peroxidase (HRP) labelling was then performed to evaluate the possibility of newly established neural pathways. Results of the CSSEP testing revealed that flaps possessing 10 nerve grafts (group 2) demonstrated better sensation when compared to flaps possessing five nerve grafts (group 1) or no nerve grafts (control group). Furthermore, retrograde HRP labelling proved that a new neural pathway had been established from the skin island to the dorsal root ganglia of S1 and S2 via the interposed nerve grafts and the sensory neurotised gracilis muscle in groups 1 and 2 rabbits. The control group did not display any sensory regeneration.
Assuntos
Músculo Esquelético/inervação , Transferência de Nervo/métodos , Retalhos Cirúrgicos/inervação , Animais , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Músculo Esquelético/fisiologia , Músculo Esquelético/transplante , Regeneração Nervosa/fisiologia , Coelhos , Retalhos Cirúrgicos/fisiologiaRESUMO
In this report, 16 patients with end-stage renal disease undergoing forearm arteriovenous shunt surgery were subjected to an ultrasound-guided axillary approach for brachial plexus nerve block. Two doses of 15 ml lidocaine 1.5% were injected using a double-shot technique The spread of the solution within the plexus sheath could be visualized using a high-resolution 12-MHz imaging probe. Most patients (94%) experienced an excellent analgesia in the regions innervated by median, ulnar and radial nerves with a lower percentage of complete analgesia (63%) in the areas innervated by musculocutaneous nerve. Three patients, who complained of pain during the surgery required further supplements of narcotics. There were no complications such as, nerve injury, puncture of the axillary vessels or other systemic reactions. This technique provides adequate analgesia - without complications and without difficulty - for extremity surgery in patients with end-stage renal diseases.