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Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage
Brett M Kissela, Mark H Eckman
BMC Neurology , 2008, DOI: 10.1186/1471-2377-8-17
Abstract: We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE). We assumed no substantial cost differences in care between the two strategies except: 1) cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408); 2) cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death); and 3) differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home), and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE.In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER < $50,000/QALY over a wide range of sensitivity analyses. Sensitivity analyses showed that the cost of rFVIIa must exceed $14,500, or the frequency of ATE exceed 29%, for the mCER to exceed $50,000/QALY. Varying the cost and/or reducing the utility of health states following ATE did not impact results.Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.The majority of strokes worldwide are ischemic. Ischemic stroke victims that present within three hours are eligible for thrombolytic treatment with intravenous recombinant tissue plasminogen activator (r-tPA). This is a costly medication (retail price is approximately $2000) that is currently
Predicting Mortality and Functional Outcomes after Ischemic Stroke: External Validation of a Prognostic Model  [PDF]
Achala Vagal, Heidi Sucharewv, Christopher Lindsell, Dawn Kleindorfer, Kathleen Alwell, Charles J. Moomaw, Daniel Woo, Matthew Flaherty, Pooja Khatri, Opeolu Adeoye, Simona Ferioli, Jason Mackey, Sharyl Martini, Felipe De Los Rios La Rosa F., Brett Kissela
Journal of Behavioral and Brain Science (JBBS) , 2018, DOI: 10.4236/jbbs.2018.810036
Abstract: Background: We previously developed predictive models for 3-month mortality and modified Rankin Score (mRS) after ischemic stroke. Aim: The aim was to test model validity for 3-month mortality and mRS after ischemic stroke in two independent data sets. Methods: Our derivation models used data from 451 subjects with ischemic stroke in 1999 enrolled in the Greater Cincinnati/Northern Kentucky Stroke Study (GCKNSS). We utilized two separate cohorts of ischemic strokes through GCKNSS (460 in 2005 and 504 in 2010) to assess external validity by utilizing measures of agreement between predicted and observed values, calibration, and discrimination using Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis. Results: The 3-month mortality model performed well in the validation datasets with an average prediction error (Brier score) of 0.045 for 2005 and 0.053 for 2010 and excellent discrimination with an area under the curve of 0.86 (95% CI: 0.79, 0.93) for 2005 and 0.84 (0.76, 0.92) for 2010. Predicted 3-month mRS also performed well in the validation datasets with R2 of 0.57 for 2005 and 0.50 for 2010 and a root mean square error of 0.85 for 2005 and 1.05 for 2010. Predicted mRS tended to be higher than actual in both validation datasets. Re-estimation of the model parameters for age and severe white matter hyperintensity in both 2005 and 2010, and for diabetes in 2005, improved predictive accuracy. Conclusions: Our previously developed stroke models performed well in two study periods, suggesting validity of the model predictions.
Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes
Ritesh Kaushal, Daniel Woo, Prodipto Pal, Mary Haverbusch, Huifeng Xi, Charles Moomaw, Padmini Sekar, Brett Kissela, Dawn Kleindorfer, Matthew Flaherty, Laura Sauerbeck, Ranajit Chakraborty, Joseph Broderick, Ranjan Deka
BMC Medical Genetics , 2007, DOI: 10.1186/1471-2350-8-49
Abstract: At the APOE locus, no individual SNP was associated with SAH after correction for multiple comparisons. Haplotype analysis revealed significant association of the major haplotype (Hap1) in APOE with SAH (p = 0.001). The association stemmed from both the 5' promoter and the 3' region of the APOE gene. APOE ε2 and ε 4 were not significantly associated with SAH. No association was observed for ELN at genotype, allele, or haplotype level and our study failed to confirm previous reports of ELN association with aneurysmal SAH.This study suggests a role of the APOE gene in the etiology of aneurysmal SAH.Non-traumatic, spontaneous subarachnoid hemorrhage (SAH) affects 16,000 to 17,000 individuals each year in the United States [1-3]. SAH has a 30-day mortality rate exceeding 40%, and surviving patients often demonstrate significant morbidity [2,4]. Over 80% of SAH can be attributed to intracranial aneurysm (IA) rupture. Familial aggregation studies of SAH have consistently identified an increased risk of a first-degree relative with SAH or family history of SAH independent of smoking and hypertension [5].Variants of the apolipoprotein E (APOE) gene have been associated with Alzheimer's disease, lipid disorders and cardiovascular disease [6-8]. Previous studies have demonstrated that APOE ε4 and/or APOE ε2 are associated with lobar intracerebral hemorrhage (ICH) [9,10]. We recently reported that haplotypes which include polymorphisms in the 5' untranslated region of the APOE gene are risk factors for lobar ICH [11]. Specific to SAH, Kokubo et al. [12] found significant association of APOE ε4 with SAH in a Japanese population. Niskakangas et al. [13] reported association of APOE ε4 with adverse outcome after aneurysmal SAH. No study on other polymorphisms of APOE with regard to risk of SAH has yet been reported.In addition to APOE, the elastin (ELN) gene emerged as a putative gene for IA after linkage was found on 7q11, where ELN is located [14]. However, prior association st
The use of standardized patients for mock oral board exams in neurology: a pilot study
Brett Kissela, Steven Harris, Dawn Kleindorfer, Christopher Lindsell, Robert Pascuzzi, Daniel Woo, Jerzy Szaflarski, Daniel Kanter, Alex Schneider, Michael Sostok, Joseph Broderick
BMC Medical Education , 2006, DOI: 10.1186/1472-6920-6-22
Abstract: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process.Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general.Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency.Currently, the American Board of Psychiatry and Neurology (ABPN) utilizes a live patient hour as one form of assessing candidates during the Step Two examination. This includes thirty minutes for the candidate to obtain a history and perform a physical examination on a patient with a neurologic disorder, and is followed by questioning in which candidates explain their thought process for evaluating the patient. Concerns have been raised about the reliability and validity of this exam, since the experience is not standardized. For example, some patients may openly reveal their diagnosis, or the diagnosis may be more readily evident than for other patients. For these reasons, the ABPN plans to replace the patient hour with other forms of assessment by 2008.[1]Residency programs commonly test their residents in "mock oral board exercises" that simulate the ABPN patient hour, using actual patients wit
Professionalism education of OB/GYN resident physicians: What makes a difference?  [PDF]
Brett Worly
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.31A026

Objective: The aim of this study was to evaluate the efficacy of a new Professionalism curriculum in an Obstetrics and Gynecology (OB/GYN) residency after introducing Narrative Medicine and Professional Development/Support Group (PDSG) programs. Methods: 32 OB/GYN residents participated in this IRB approved pilot study. Twenty residents were assessed with the Barry Challenges to Professionalism Questionnaire (Barry), the Jefferson Scale of Empathy-Physician Version (JSE), and the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration (JSAT) in August 2010, as controls. Five Narrative Medicine sessions and four PDSG sessions were then used from August 2010-May 2011, for resident physician professionalism education. Seventeen residents then underwent post-testing with the Barry, JSE, and JSAT in May 2011. Results: The pre-test/post-test Barry comparison showed an improvement in scores after introduction of the new Narrative Medicine and PDSG curriculum (7.6 +/- 2.1 versus 8.4 +/- 1.6; p = 0.10) though this was not statistically significant. Pre-test/post-test comparison of JSAT scores showed a statistically significant decline in collaboration (52.3 +/- 4.1 versus 49.7 +/- 3.7; p = 0.028) while JSE scores showed a downward trend in empathy (109.3 +/- 10.0 versus 104.8 +/- 9.2; p = 0.086). Conclusion: Narrative Medicine and PDSG small group sessions could be an effective component of OB/GYN resident physician Professionalism curriculum. This pilot project was underpowered, due to limited resources.

Incorporating Uncertain Costs within a Series of Sequential Probability Ratio Tests  [PDF]
Conor McMeel, Brett Houlding
Open Journal of Statistics (OJS) , 2016, DOI: 10.4236/ojs.2016.65073
Abstract: We consider an extension to Sequential Probability Ratio Tests for when we have uncertain costs, but also opportunity to learn about these in an adaptive manner. In doing so we demonstrate the effects that allowing uncertainty has on observation cost, and the costs associated with Type I and Type II error. The value of information relating to modelled uncertainties is derived and the case of statistical dependence between the parameter affecting decision outcome and the parameter affecting unknown cost is also examined. Numerical examples of the derived theory are provided, along with a simulation comparing this adaptive learning framework to the classical one.
Human Health, Rights and Wind Turbine Deployment in Canada  [PDF]
Carmen Krogh, Brett Horner
Open Journal of Social Sciences (JSS) , 2017, DOI: 10.4236/jss.2017.55012
Abstract: Canada has ratified international conventions which recognize the individual’s right to the enjoyment of the highest attainable standard of health. Despite the adoption of these covenants governments sometimes support policies and practises which trade off individual human health with other conflicting interests. This review evaluates the individual’s right to health against government policies and practices which support wind energy deployment in Canada. Our analysis presents government documents, peer reviewed literature, and other references which support the conclusion that wind energy deployment in Canada can be expected to result in avoidable harm to human health. This harm conflicts with contemporary health and social justice principles. Governments have a responsibility to help Canadians maintain and improve their health by generating effective responses for the prevention of avoidable harm. Individuals have a right to make informed decisions about their health. Knowledge gaps and potential risks to health should be fully disclosed. Individuals should not be exposed to industrial wind turbines without their informed consent.
The Influence of Morinda citrifolia (Noni) Fruit Juice on Collagen Deposition in the Skin: A Minireview  [PDF]
Brett J. West
Journal of Biosciences and Medicines (JBM) , 2018, DOI: 10.4236/jbm.2018.69001
Abstract: The fruit of Morinda citrifolia, commonly known as noni, has an extensive history of use as a food and medicine throughout the tropics. Among its many uses, noni was believed to promote skin health. In vivo wound healing studies reveal that noni fruit juice ingestion increases collagen production and deposition via increased expression of extracellular matrix protein genes. Noni juice also appears to promote fibroblast proliferation. In vitro studies indicate that noni juice also protects fibroblasts via activation of the transcription factor Nrf2 and protects extracellular matrix collagen by inhibiting matrix metalloproteinases. In vitro and in vivo study findings are corroborated by a clinical trial where hospitalization times were reduced, and wound granulation quality was improved in pediatric burn patients. The findings of other human studies also indicate that noni juice has the potential to protect skin collagen. These include reduced plasma reactive oxygen species in cigarette smokers, lowered skin glycation levels in overweight and obese adults, as well as reduced skin glycation levels among noni juice consumers within the general population. These in vitro, in vivo and human studies reveal that there are multiple mechanisms of action through which noni juice promotes collagen synthesis and inhibits collagen degradation. The procollagen properties of noni juice aid wound healing, increase skin elasticity, and improve the overall appearance of the skin.
Science review: The use of proton pump inhibitors for gastric acid suppression in critical illness
Stephen Brett
Critical Care , 2004, DOI: 10.1186/cc2980
Abstract: Stress-related mucosal damage (SRMD) is an erosive gastritis of unclear pathophysiology, which can occur rapidly after a severe insult such as trauma, surgery, sepsis or burns. SRMD is apparent in 75–100% of critically ill patients within 24 hours of admission to an intensive care unit (ICU) [1,2]. Clinically important bleeding, defined as macroscopic bleeding resulting in hemodynamic instability or the need for red blood cell transfusion, occurs as a result of SRMD in about 3.5% of ICU patients who are mechanically ventilated for 48 hours or more [3]. Along with mechanical ventilation, risk factors for clinically important bleeding from SRMD include coagulopathy, shock, severe burns, a history of gastrointestinal (GI) ulceration, and multiple organ failure [4,5]. Bleeding is associated with a 20–30% increase in absolute risk of mortality, and with an increase of 1–4 in relative risk [3]. In addition, it increases the demand on limited blood stocks and extends the length of ICU stay by about 4–8 days [3], thereby adding to overall management costs.To avert these consequences, prophylaxis has been recommended for all ICU patients at high risk of SRMD [4,5]. Stress ulcer prophylaxis is included in the care bundle for critically ill patients on mechanical ventilation recommended by the Institute for Healthcare Improvement and adopted by the National Health Service Modernization agency in the UK [6]. The Surviving Sepsis Campaign, an international initiative founded by the European Society of Intensive Care Medicine, the Society of Critical Care Medicine and the International Sepsis Forum, has also recommended that prophylaxis be a part of critical care [7]. Specific risk factors for SRMD include: mechanical ventilation (more than 48 hours), coagulopathy, neurosurgery, any kind of shock, respiratory failure, sepsis, polytrauma, tetraplegia, severe burns (more than 30%) and multiple organ failure [4,5]. Patients in the ICU with a history of gastric or duodenal ulceration
A bill of wron
Brett, Guy;
ARS (S?o Paulo) , 2009, DOI: 10.1590/S1678-53202009000100007
Abstract: the author discusses the procedures of accumulation and serialization on the production of brazilian artist jac leirner, focusing works from the late nineteen eighties, such as "os cem" the hundreds (1985-7), "pulm?o" lung (1987) and "primeiros erros" first errors.
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