66 research outputs found
Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients
BACKGROUND: Clinical trials have shown low-molecular weight heparin (LMWH) to be at least as safe and efficacious as unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in acutely-ill medical inpatients. OBJECTIVE: To compare clinical and economic outcomes among acutely-ill medical inpatients receiving the LMWH enoxaparin versus UFH prophylaxis in clinical practice. METHODS: Using a large, multi-hospital, US database, we identified persons aged â„40 years hospitalized for â„6 days for an acute medical condition (including circulatory disorders, respiratory disorders, infectious diseases, or neoplasms) from Q4 1999 to Q1 2002. From these patients, those who received thromboprophylaxis with either enoxaparin or UFH were identified. Surgical patients and those requiring or ineligible for anticoagulation were excluded. We compared the incidence of deep-vein thrombosis (DVT), pulmonary embolism (PE), and all VTE (i.e., DVT and/or PE). Secondary outcomes were occurrence of side-effects, length of hospital stay and total costs. RESULTS: 479 patients received enoxaparin prophylaxis and 2,837 received UFH. The incidence of VTE was 1.7% with enoxaparin prophylaxis versus 6.3% with UFH (RR = 0.26; p < 0.001). Occurrence of side effects, length of stay (10.00 days with enoxaparin vs. 10.26 days with UFH; p = 0.348) and total costs (17,602; p = 0.463) were similar in the 2 groups. CONCLUSION: We observed a 74% lower risk of VTE among patients receiving enoxaparin prophylaxis versus UFH prophylaxis. There was no significant difference in side effects or economic outcomes. These results provide evidence that the LMWH enoxaparin is more effective than UFH in reducing the risk of VTE in current clinical practice
Recommended from our members
Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States
Background: High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (âfluâ) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods: We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009â2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results: In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of 1.0 B compared to PCV7. Conclusions: In a flu pandemic similar to the 2009â2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs
Recommended from our members
Cost-Effectiveness Analysis of Tdap in the Prevention of Pertussis in the Elderly
Objectives: Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap) immunization among adults â„65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to include adults â„65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination. Methods: We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25â200 cases per 100,000), due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US336,000, 17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario analyses. Conclusions: Tdap immunization of adults aged 65 years according to current ACIP recommendations is a cost-effective health-care intervention at plausible incidence assumptions
Recommended from our members
Cost-Effectiveness of Tdap Vaccination of Adults Aged â„65 Years in the Prevention of Pertussis in the US: A Dynamic Model of Disease Transmission
Objectives: In February 2012, the Advisory Committee on Immunization Practices (ACIP) advised that all adults aged â„65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap), expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged â„65 to âbaselineâ practice [full-strength DTaP administered from 2 months to 4â6 years, and one dose of Tdap at 11â64 years replacing decennial Td booster], using a dynamic model. Methods: We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged â„65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care) and quality-adjusted life-years (QALYs) associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges. Results: For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants) of pertussis annually at steady state. Additional vaccination costs are 47.7 million (societal perspective) and $44.8 million (payer perspective). From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs) versus baseline. Results are robust to sensitivity analyses and alternative scenarios. Conclusions: Immunization of eligible adults aged â„65, consistent with the current ACIP recommendation, is cost saving from both payer and societal perspectives
Recommended from our members
Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data
Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged â€59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort
Defining a link with asthma in mice congenitally deficient in eosinophils
Eosinophils are often dominant inflammatory cells present in the lungs of asthma patients. Nonetheless, the role of these leukocytes remains poorly understood. We have created a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells. Allergen challenge of PHIL mice demonstrated that eosinophils were required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma. The development of an eosinophi-less mouse now permits an unambiguous assessment of a number of human diseases that have been linked to this granulocyte, including allergic diseases, parasite infections, and tumorigenesis
Economic Model of a Birth Cohort Screening Program for Hepatitis C Virus
Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening (53.7 billion), but yields lower costs related to advanced liver disease (39.8 billion); birth-cohort screening produces an incremental costeffectiveness ratio (ICER) of 5 billion per year, 4 with projected HCV-related societal costs for the years 2010-2019 estimated to total $54.2 billion. 5 For the last decade, the standard of care for treating HCV has been the combination of pegylated interferon (Peg-IFN) and ribavirin (RBV), 6 which successfully eradicates virus (sustained virologic response; SVR) in 40%-80% of treated patients
Orbital effects of a monochromatic plane gravitational wave with ultra-low frequency incident on a gravitationally bound two-body system
We analytically compute the long-term orbital variations of a test particle
orbiting a central body acted upon by an incident monochromatic plane
gravitational wave. We assume that the characteristic size of the perturbed
two-body system is much smaller than the wavelength of the wave. Moreover, we
also suppose that the wave's frequency is much smaller than the particle's
orbital one. We make neither a priori assumptions about the direction of the
wavevector nor on the orbital geometry of the planet. We find that, while the
semi-major axis is left unaffected, the eccentricity, the inclination, the
longitude of the ascending node, the longitude of pericenter and the mean
anomaly undergo non-vanishing long-term changes. They are not secular trends
because of the slow modulation introduced by the tidal matrix coefficients and
by the orbital elements themselves. They could be useful to indepenedently
constrain the ultra-low frequency waves which may have been indirectly detected
in the BICEP2 experiment. Our calculation holds, in general, for any
gravitationally bound two-body system whose characteristic frequency is much
larger than the frequency of the external wave. It is also valid for a generic
perturbation of tidal type with constant coefficients over timescales of the
order of the orbital period of the perturbed particle.Comment: LaTex2e, 24 pages, no figures, no tables. Changes suggested by the
referees include
Modification and preservation of environmental signals in speleothems
Speleothems are primarily studied in order to generate archives of climatic change and results have led to significant advances in identifying and dating major shifts in the climate system. However, the climatological meaning of many speleothem records cannot be interpreted unequivocally; this is particularly so for more subtle shifts and shorter time periods, but the use of multiple proxies and improving understanding of formation mechanisms offers a clear way forward. An explicit description of speleothem records as time series draws attention to the nature and importance of the signal filtering processes by which the weather, the seasons and longer-term climatic and other environmental fluctuations become encoded in speleothems. We distinguish five sources of variation that influence speleothem geochemistry: atmospheric, vegetation/soil, karstic aquifer, primary speleothem crystal growth and secondary alteration and give specific examples of their influence. The direct role of climate diminishes progressively through these five factors. \ud
\ud
We identify and review a number of processes identified in recent and current work that bear significantly on the conventional interpretation of speleothem records, for example: \ud
\ud
1) speleothem geochemistry can vary seasonally and hence a research need is to establish the proportion of growth attributable to different seasons and whether this varies over time. \ud
\ud
2) whereas there has traditionally been a focus on monthly mean ĂïżœĂÂŽ18O data of atmospheric moisture, current work emphasizes the importance of understanding the synoptic processes that lead to characteristic isotope signals, since changing relative abundance of different weather types might 1Corresponding author, fax +44(0)1214145528, E-mail: [email protected] control their variation on the longer-term. \ud
\ud
3) the ecosystem and soil zone overlying the cave fundamentally imprint the carbon and trace element signals and can show characteristic variations with time. \ud
\ud
4) new modelling on aquifer plumbing allows quantification of the effects of aquifer mixing. \ud
\ud
5) recent work has emphasized the importance and seasonal variability of CO2-degassing leading to calcite precipitation upflow of a depositional site on carbon isotope and trace element composition of speleothems. \ud
\ud
6) Although much is known about the chemical partitioning between water and stalagmites, variability in relation to crystal growth mechanisms and kinetics is a research frontier. \ud
\ud
7) Aragonite is susceptible to conversion to calcite with major loss of chemical information, but the controls on the rate of this process are obscure. \ud
\ud
Analytical factors are critical to generate high-resolution speleothem records. A variety of methods of trace element analysis are available, but standardization is a common problem with the most rapid methods. New stable isotope data on Irish stalagmite CC3 compares rapid laser-ablation techniques with the conventional analysis of micromilled powders and ion microprobe methods. A high degree of comparability between techniques for ĂïżœĂÂŽ18O is found on the mm-cm scale, but a previously described high-amplitude oxygen isotope excursion around 8.3 ka is identified as an analytical artefact related to fractionation of the laser-analysis associated with sample cracking. High-frequency variability of not less than 0.5o/oo may be an inherent feature of speleothem ĂïżœĂÂŽ18O records
Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function
Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometryâbased proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membraneâbound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells
- âŠ