tbuckley/cabot-search huggingface dataset:
Reporting Cost-effectiveness Analyses With Confidence
Authors: R. L. Obenchain
Journal: JAMA (1997)

<h3>To the Editor.</h3> —One of the recommendations made by Dr Siegel and colleagues<sup>1</sup>in their article on reporting cost-effectiveness analyses is that cost-effectiveness ratios should not appear for options that are less effective but more costly than an alternative (ie, are dominated). We agree with this approach when costs and effects are expressed as point estimates.<sup>2</sup>However, the increasing frequency with which pharmacoeconomic evaluations are conducted alongside clinical trials makes it possible to express costs and effects as means and variances and to compare them by using confidence intervals (CIs). The use of CIs makes it possible to measure uncertainty related to variability in sample data.<sup>3</sup>In this case, the CI of the cost-effectiveness ratio could range from a negative value to a positive one. This situation may occur, for instance, if sample size is not large enough to demonstrate statistically significant differences from a clinical perspective,
Cytotoxic effect of asbestos on macrophages in different activation states.
Authors: A Wright, K Donaldson, J M Davis
Journal: Environmental Health Perspectives (1983)

The in vitro effects due to phagocytosis of asbestos by mouse peritoneal macrophages in various stages of activation have been compared. The amphiboles proved relatively inert; chrysotile, however, expressed a greater degree of cytotoxicity toward those populations of macrophages induced in vivo with asbestos, than toward any of the other populations of cells. These results are compared with data concerning the enzyme release from the different populations of macrophages following phagocytosis of asbestos. The results indicate that those macrophages that have been exposed to a prior stimulation of either amphibole or serpentine asbestos in vivo are particularly sensitive to exposure to a second dose of a toxic fiber.
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS)
Authors: Lorraine A. Everett, Benjamin Glaser, John C. Beck, Jacquelyn R. Idol, Andreas Buchs, Ma'ayan Heyman, Faiad Adawi, Elizur Hazani, Elias Nassir, Andreas D. Baxevanis, Val C. Sheffield, Eric D. Green
Journal: Nature Genetics (1997)
Cost of Medical Care
Authors: William MacMillan Rodney
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Dr Markle's thoughts (239:1629, 1978) on cost awareness reiterate those of a slightly more formal survey recently published.<sup>1</sup>It is not that physicians in the private sector forget incurred costs with the pressure of day-to-day patient care. The fact that residents in training performed equally poorly reflects the lack of fiscal responsibility inherent in the educational process. Third-party sources are presently attempting to engage public awareness. Yearly physician Medicare collections have been published by the Department of Health, Education, and Welfare, and Blue Cross patients receive an itemized account of all reimbursements on their behalf. A more productive approach is directed cost-awareness training during the formative educational experiences of those soon to wield the technological imperative. The recent explosion of funding for cost-containment teaching programs has been noted (<i>Am Med News</i>21:22-23, April 21, 1978). At my clinic we have made an overt attempt to recognize
Abstract P6-10-01: A randomized phase 2 study of the antibody-drug conjugate CDX-011 in advanced GPNMB-overexpressing breast cancer: The EMERGE study
Authors: DA Yardley, R Weaver, ME Melisko, MN Saleh, FP Arena, A Forero, T Cigler, A Stopeck, D Citron, I Oliff, R Bechhold, R Loutfi, A Garcia, E Crowley, J Green, MJ Yellin, TA Davis, LT Vahdat
Journal: Cancer Research (2012)

Abstract Background: GPNMB is an internalizable transmembrane glycoprotein overexpressed in multiple tumor types, including breast cancer (BC). GPNMB promotes BC metastases in a murine model and is a poor prognostic marker in patients (pts) (Rose 2010). CDX-011 (glembatumumab vedotin) is a fully human GPNMB-specific monoclonal antibody conjugated to the potent cellular toxin MMAE via a protease-sensitive peptide linker, designed to cleave upon cellular internalization. In Phase I/II studies of CDX-011 in BC (n = 42), an objective response rate (ORR) (including confirmed and unconfirmed response) of 12% overall and 20% for “triple-negative” (ER/PR/HER2−; TN) pts was observed (Saleh, ASCO 2010). Methods: The Phase II EMERGE study examined the efficacy of CDX-011 by level of GPNMB expression. Refractory BC (2–7 prior cytotoxic regimens in metastatic setting), GPNMB expression in ≥ 5% of tumor or stroma cells (as centrally determined on archival tumor), and no persistent treatment-related toxicity (including neuropathy) of ≥ Grade 2 severity were required for enrollment. Pts were stratified by GPNMB expression pattern (any tumor, low stromal or high stromal) and randomized 2:1 to CDX-011 (1.88 mg/kg IV q 21 days) or “investigator's choice” (IC) single-agent chemotherapy, and treated until progression (PD) or intolerance with IC pt crossover permitted to CDX-011 at PD. Endpoints: ORR (primary), progression-free survival (PFS), safety, pharmacokinetics, pharmacodynamics. Results: 99% of screened tumor samples expressed GPNMB. 122 treated pts (81 CDX-011 vs. 41 IC) had median age = 56 vs. 56 years; median # prior anticancer regimens = 6 vs. 5; visceral disease (liver/lung) = 83% vs. 80%; TN = 33% vs 27%, respectively. To date, 15 IC pts have crossed over to CDX-011, and 14 pts (8 CDX-011, 6 IC) continue on treatment. CDX-011 was well tolerated with less hematologic toxicity than IC; CDX-011-related toxicity included rash (overall = 38%; Grade 1 = 20%; Grade 2 = 15%; Grade 3 = 3%) and neuropathy (overall = 18%; Grade 1 = 8%; Grade 2 = 7%; Grade 3 = 2%). Conclusions: CDX-011 was a well-tolerated and active agent in this heavily pre-treated BC pt population. Preliminary analysis of the EMERGE study demonstrates enhanced activity of CDX-011 in TN as well as high GPNMB expressing BC tumors, confirming that CDX-011 is a targeted agent. This noted promising activity in advanced TN and hGPNMB enriched pt populations warrants further evaluation. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-10-01.
More on maps, terrains, and behaviors
Authors: R. Alexander Bentley, Michael J. O'Brien, William A. Brock
Journal: Behavioral and Brain Sciences (2014)

Abstract In a recent New York Times column (April 15, 2013), David Brooks discussed how the big-data agenda lacks a coherent framework of social theory – a deficiency that the Bentley, O'Brien, and Brock (henceforth BOB) model was meant to overcome. Or, stated less pretentiously, the model was meant as a first step in that direction – a map that hopefully would serve as a minimal, practical, and accessible framework that behavioral scientists could use to analyze big data. Rather than treating big data as a record of, and also a predictor of, where and when certain behaviors might take place, the BOB model is interested in what big data reveal about how decisions are being made, how collective behavior evolves from daily to decadal time scales, and how this varies across communities.
Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport
Authors: Coen C. Paulusma, Annemiek Groen, Cindy Kunne, Kam S. Ho-Mok, Astrid L. Spijkerboer, Rudi D. de Waart, Frans J. Hoek, Heleen Vreeling, Kees A. Hoeben, Jan van Marle, Ludmila Pawlikowska, Laura N. Bull, Alan F. Hofmann, A. S. Knisely, Ronald P. J. Oude Elferink
Journal: Hepatology (2006)

Progressive familial intrahepatic cholestasis type 1 (PFIC1, Byler disease, OMIM 211600) is a severe inherited liver disease caused by mutations in ATP8B1 . ATP8B1 is a member of the type 4 subfamily of P-type ATPases, which are phospholipid flippases. PFIC1 patients generally develop end-stage liver disease before the second decade of life. The disease is characterized by impaired biliary bile salt excretion, but the mechanism whereby impaired ATP8B1 function results in cholestasis is unclear. In a mouse model for PFIC1, we observed decreased resistance of the hepatocanalicular membrane to hydrophobic bile salts as evidenced by enhanced biliary recovery of phosphatidylserine, cholesterol, and ectoenzymes. In liver specimens from PFIC1 patients, but not in those from control subjects, ectoenzyme expression at the canalicular membrane was markedly deficient. In isolated mouse livers Atp8b1 deficiency impaired the transport of hydrophobic bile salts into bile. In conclusion , our study shows that Atp8b1 deficiency causes loss of canalicular phospholipid membrane asymmetry that in turn renders the canalicular membrane less resistant toward hydrophobic bile salts. The loss of phospholipid asymmetry may subsequently impair bile salt transport and cause cholestasis. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Restenosis After Experimental Angioplasty
Authors: Antoine Lafont, Luis A. Guzman, Patrick L. Whitlow, Marlene Goormastic, J. Fredrick Cornhill, Guy M. Chisolm
Journal: Circulation Research (1995)

Abstract Predicting and preventing arterial restenosis after angioplasty has failed despite considerable research into mechanisms and techniques. We examined the roles of chronic constriction, neointimal-medial growth, and adventitial changes in restenosis in atherosclerotic rabbits. Angioplasty was performed on femoral artery lesions 4 weeks after lesion induction by air drying and cholesterol-supplemented diet. Angiographic and histological evaluation was conducted 3 to 4 weeks after angioplasty. The angiographic minimum luminal diameter (MLD) increased from 1.31±0.21 to 1.73±0.41 mm after angioplasty. Loss in MLD by 3 to 4 weeks was 0.95±0.64 mm. Initial gain and late loss correlated ( P =.008). Late residual stenosis, defined histologically as the difference between the luminal areas of a proximal reference site and lesion site normalized by the luminal area of the reference site, was 52±32%. Histological indices of chronic constriction, neointimal-medial growth, and adventitial growth were defined on the basis of the areas of these arterial wall layers at the lesion site relative to the reference site. Another parameter defined as the ratio of adventitial area to the area of intima+media at the lesion site allowed evaluation of the relative importance of these layers. Surprisingly, late residual stenosis correlated with chronic constriction ( P =.0003) but not with neointimal-medial growth or adventitial growth. The ratio of adventitial area to the area of intima+media at the lesion site also correlated with chronic constriction ( P =.01). These findings suggest that factors related to arterial remodeling rather than neointimal-medial growth may dominate the response to angioplasty.
Clinical Worth of Adiponectin Levels in Obesity and Glycemic Control of Japanese Type 2 Diabetic Patients
Authors: Katsunori Nonogaki, Hiroaki Kumano, Yoshihiko Ootsuka, Aya Takeuchi, Naohiko Nonogaki, Tomifusa Kuboki
Journal: Diabetes Care (2003)

Low levels of adiponectin in plasma have recently been implicated in the development of obesity, insulin resistance, and type 2 diabetes in mice and humans (1–4). We examined a role of adiponectin as a clinical examination in obesity and type 2 diabetes and raise a question of clinical worth of evaluating adiponectin levels in the management of type 2 diabetic patients.

In the first group, 39 Japanese subjects with type 2 diabetes, including 19 men and 20 women matched for age, HbA1c, and plasma glucose levels, were assessed in a cross-sectional analysis. Plasma adiponectin levels were determined in type 2 diabetic subjects with normal BMI …
Twenty-Four Hour Patterns of Plasma Luteinizing Hormone and Follicle-Stimulating Hormone in Sexual Precocity
Authors: Robert M. Boyar, Jordan W. Finkelstein, Ralph David, Howard Roffwarg, Sheldon Kapen, Elliot D. Weitzman, Leon Hellman
Journal: New England Journal of Medicine (1973)

To evaluate the secretory patterns of luteinizing and follicle-stimulating hormones in various forms of sexual precocity, plasma levels of these hormones were measured every 20 minutes for 24 hours in six patients and nine normal pubertal children. Three patients with "idiopathic" precocious puberty and one boy with a hypothalamic tumo rand precocious puberty exhibited fluctuating plasma concentrations that resembled findings in normal pubertal children in that they had significantly increased luteinizing hormone concentrations during sleep. Two boys with congenital adrenal hyperplasia and advanced bone age also showed episodic fluctuation of both hormones and augmented luteinizing hormone concentrations during sleep. These findings show that patients with precocious puberty related either to Central-nervous-system stimulation or to a primary adrenal disorder can exhibit the normal pubertal luteinizing hormone pattern of augmented secretory activity synchronous with sleep. (N Engl J Med 289:282–286, 1973)
NHS computer programme is “roughly to timetable,” IT chief says
Authors: Michael Cross
Journal: BMJ (2006)

The leader of the controversial scheme to computerise the NHS in England has defended the £20bn (€29bn; $37bn) programme in advance of critical scrutiny by auditors and parliament. Richard Granger, chief executive of NHS Connecting for Health, last week described progress on the national programme for information technology (IT) as “roughly to timetable.”

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Richard Granger: “I thought that saving thousands of lives would be a largely uncontroversial activity. I believe that's what's called naive.”

Credit: NHS CONNECTING FOR HEALTH

Mr Granger accused …

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Analysis of hurling and camogie injuries.
Authors: P J Crowley, K C Condon
Journal: British Journal of Sports Medicine (1989)

In 1984, 4500 people with sport injuries attended the Cork Regional Hospital. Of these, 817 were injured in the national game of hurling and camogie. Hand injuries were the most frequent occurring in approximately one third of injured players (33 per cent) and of these, just half had a closed metacarpal fracture. Facial injuries were the second most frequent category (28 per cent). Almost one third of these were nasal fractures, while forehead and eyebrow lacerations, fractured zygoma, loss of teeth are also common. Sport eye injuries referred to the Eye, Ear and Throat Hospital in Cork during the same period amounted to 107, of which 26 occurred in hurling. It is believed that a properly designed protective head gear would largely eliminate such facial and eye injuries.
UK nears European average in proportion of GDP spent on health care
Authors: Anne Griffin
Journal: BMJ (2007)

Cyclo-oxygenase-2 (COX 2) inhibitors should be used only as the last choice after other types of non-steroidal anti-inflammatory drugs (NSAIDs) to relieve chronic pain in people with heart disease or at high risk of it, the American Heart Association has recommended.Its statement, published online in Circulation on 26 February (http://circ.ahajournals.orgdoi:10.1161/circulationaha.106.181424), was designed to end any remaining confusion about the cardiovascular risk of these agents.The association has recommended a stepped approach to treatment.The first step should be non-pharmacological approaches, such as physical therapy and weight loss, for patients with known cardiovascular disease or with risk factors for ischaemic heart disease.Drug treatment should start with agents with the lowest reported risk of cardiovascular events, before other agents are prescribed, and at each step account should be taken of the risk-benefit balance.First line drug choices include paracetamol (acetaminophen), aspirin, tramadol, and short term use of other narcotic analgesics.If these fail to achieve adequate pain control, the next option is non-acetylated salicylates, such as naproxen.The association recommended NSAIDs that aren't COX 2 inhibitors if pain is still inadequately controlled, then NSAIDs with some COX 2 activity as the next step, and lastly COX 2 selective NSAIDs.The committee considered the risk of all three of these classes to be sufficiently high to require that patients taking them should be monitored regularly for sustained hypertension (or worsening of prior blood pressure control), oedema, worsening renal function, or gastrointestinal bleeding.See pp 436, 450. Save COX 2 inhibitors till last for cardiac patientsUK NEWS HFEA allows women to donate eggs for research, p445 World NEWS repeal law that puts "FdA on the payroll of the industry", p447 bmj.comUK government defeated on community treatment forms
Nonthoracotomy- versus thoracotomy-implantable defibrillators. Intention-to-treat comparison of clinical outcomes.
Authors: J M Kleman, L W Castle, G A Kidwell, J D Maloney, V A Morant, R G Trohman, B L Wilkoff, P M McCarthy, S L Pinski
Journal: Circulation (1994)

Nonthoracotomy-implantable cardioverter/defibrillator (ICD) systems may represent a significant advance in the treatment of patients with life-threatening ventricular arrhythmias, but their merits relative to those of the well-established thoracotomy systems remain largely unknown. The objective of this study was to compare the short- and long-term clinical outcomes after attempted ICD implantation via a nonthoracotomy versus thoracotomy approach in similar groups of patients.Between September 1990 and December 1992, 212 consecutive patients underwent attempted ICD system implantation without concomitant cardiac surgery at a single institution. Approach selection was not randomized but rather was based primarily on hardware availability. Primary comparisons of short- and long-term outcome were performed according to the "intention-to-treat" principle. Implantation was attempted via a nonthoracotomy approach in 120 patients (57%) and via a thoracotomy approach in 92 patients (43%). Prior cardiac surgery was more prevalent in the nonthoracotomy patients; otherwise, groups did not differ significantly in terms of prognostically relevant clinical characteristics. Nonthoracotomy implantation was successful in 101 patients (84%). After crossover to thoracotomy implantation (14 patients), the eventual success rate for ICD system implantation was 96% in the nonthoracotomy group. Thoracotomy implantation was successful in 89 patients (97%). Operative mortality was 3.3% in the nonthoracotomy and 4.3% in the thoracotomy groups (P = .73). Nonthoracotomy group patients were less likely to experience postoperative congestive heart failure (6% versus 16%; P = .02) or supraventricular arrhythmia (6% versus 18%; P = .004) and had significantly shorter postoperative intensive care and total hospitalization. Total hospital costs were significantly lower in the nonthoracotomy group ($32,205 versus $37,265; P = .001). After a follow-up of 16 +/- 9 months, there were 17 deaths in the nonthoracotomy group (none sudden) and 12 deaths in the thoracotomy group (1 sudden). One- and 2-year Kaplan-Meier survival probabilities were .87 (95% CI, .78 to .91) and .80 (95% CI, .68 to .88) in the nonthoracotomy group and .90 (95% CI, .82 to .95) and .87 (95% CI, .77 to .93) in the thoracotomy group (P = .56; log-rank test).Nonthoracotomy ICD implantation is associated with reduced surgical morbidity, postoperative hospital care requirement, and hospital costs and has similar efficacy in preventing sudden death relative to the thoracotomy approach. From these nonrandomized data, it appears that a nonthoracotomy approach should be considered preferable in most patients requiring ICD therapy.
Evidence-Based Cardiology
Authors: Roy C. Ziegelstein
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes2 January 2001Evidence-Based CardiologyRoy C. Ziegelstein, MDRoy C. Ziegelstein, MDJohns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, Maryland. (Ziegelstein)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-1-200101020-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Sharis PJ, Cannon CP. 384 pages. Philadelphia: Lippincott Williams & Wilkins; 2000. $39.95. ISBN 0781716136. Order phone 800-638-0672.Field of medicine: Cardiology.Format: Softcover book.Audience: Practicing internists and cardiologists and trainees.Purpose: To summarize data from major clinical trials in six major topic areas of cardiology.Content: The first chapter discusses risk factors for coronary artery disease, and the second covers invasive procedures and coronary revascularization. Two chapters present data on acute coronary syndromes. The book concludes with one chapter each on congestive heart failure and arrhythmia.Highlights: The book offers a comprehensive review of the major clinical trials ... Author, Article, and Disclosure InformationAffiliations: Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, Maryland. (Ziegelstein) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 January 2001Volume 134, Issue 1Page: 88KeywordsArrhythmiaC-reactive proteinsClinical trialsCoronary revascularizationDiabetes mellitusHeart failureMedical risk factorsMortalitySoftware toolsStable coronary artery disease ePublished: 2 January 2001 Issue Published: 2 January 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comment on: Wehr et al. Low Free Testosterone Levels Are Associated With All-Cause and Cardiovascular Mortality in Postmenopausal Diabetic Women. Diabetes Care 2011;34:1771–1777
Authors: Nitesh D. Kuhadiya, Sandeep Dhindsa, Paresh Dandona
Journal: Diabetes Care (2012)

We have read with immense interest the recent article by Wehr et al. (1) showing that low free testosterone concentrations in postmenopausal diabetic women are associated with increased all-cause and cardiovascular mortality. We wish to comment on the concentrations of total and free testosterone of the study subjects. The overall mean or median total and free testosterone concentrations were not mentioned. However, according to quartiles based on free testosterone, the mean free testosterone was 0.93 ng/mL (equivalent to 93 ng/dL). The total testosterone at the intersection of second and …