tbuckley/cabot-search huggingface dataset:
ACC/AHA Classification of Care Metrics: Performance Measures and Quality Metrics
Authors: Robert O. Bonow, Frederick A. Masoudi, John S. Rumsfeld, Elizabeth DeLong, N.A. Mark Estes, David C. Goff, Kathleen Grady, Lee A. Green, Ann R. Loth, Eric D. Peterson, Ileana L. Piña, Martha J. Radford, David M. Shahian
Journal: Circulation (2008)

The American College of Cardiology (ACC) and the American Heart Association (AHA) have provided leadership in enhancing the quality of cardiovascular care, including the development of clinical performance measures and clinical registries that permit the evaluation of quality of care and stimulate quality improvement. Compliance with ACC/AHA performance measures and metrics encourages the provision of the strongest evidence-based quality of care, including therapies that are life-extending or life-enhancing. Among quality metrics, only a subset should be considered performance measures-that is, those measures specifically suitable for public reporting, external comparisons, and possibly pay-for-performance programs, in addition to quality improvement. These performance measures have been developed using ACC/AHA methodology, often in collaboration with other organizations, and include the process of public comment and peer review. Quality metrics are those measures that have been developed to support self assessment and quality improvement at the provider, hospital, and/or health care system level. These metrics represent valuable tools to aid clinicians and hospitals in improving quality of care and enhancing patient outcomes, but may not meet all specifications of formal performance measures. These quality metrics may also be considered "candidate" measures that with further research or field testing would meet the criteria for formal performance measures in the future. This measure classification is intended to aid providers, hospitals, health systems, and payers in identifying those measures that the ACC and AHA formally endorse as performance measures, while at the same time promoting the broader range of clinical metrics that are useful for quality improvement efforts.
Staffing issues are often to blame for poor NHS performance, says regulator
Authors: J. Wise
Journal: BMJ (2012)

High BP is a major risk factor for atherosclerotic cardiovascular disease mortality in the general population. Surprising, studies that have been conducted among hemodialysis (HD) patients have yielded conflicting data on the relationship between BP and mortality. This study explores two hypotheses among HD patients: (<i>1</i>) The relationship between BP and mortality changes over time, and (<i>2</i>) mild to moderate hypertension is well tolerated. Incident HD patients who were treated at Dialysis Clinic Inc. facilities between 1993 and 2003 were studied. Primary end points were atherosclerotic cardiovascular disease and all-cause mortality. The relationship between BP and mortality was analyzed in two sets of Cox proportional hazards models. Model-B explored the relationship between baseline BP and mortality in sequential time periods. Model-TV assessed the relationship between BP, treated as time-varying, and mortality. The study sample (<i>n</i> = 16,959) was similar in characteristics to the United States Renal Data Systems population, although black patients were slightly overrepresented. Model-B demonstrated that the relationship between baseline BP and mortality changes over time. Low systolic BP (&lt;120 mmHg) was associated with increased mortality in years 1 and 2. High systolic BP (≥150 mmHg) was associated with increased mortality among patients who survived ≥3 yr. Low pulse pressure was associated with increased mortality. Model-TV demonstrated that mild to moderate systolic hypertension may be relatively well tolerated. In conclusion, the relationship between baseline BP and mortality changes over time. Mild to moderate systolic hypertension was associated with only modest increases in mortality.
Reply to F. Perrone et al
Authors: C. Daniel Mullins, Amy P. Abernethy, Arif Hussain, Russ W. Montgomery, Steven D. Pearson, Sean Tunis
Journal: Journal of Clinical Oncology (2012)

We appreciate the favorable comments of Perrone et al 1 and their interest in our article. 2 We also appreciate the extent of their previous research in related areas.Their comments highlight the need for better evidence of the effectiveness of oncology drugs and a better means for using the best available evidence to inform coverage decisions.That is the intent of our effectiveness guidance document, and we are optimistic that our guidance, along with other guidance and reports, will motivate future trials that address the many evidence gaps that exist in adult oncology.As Perrone et al 1 suggested, our guidance may well serve to improve the design of oncology trials for expanded indications of drugs that are used off label.We briefly comment on this possibility in the Scope and Purpose of Effectiveness Guidance Document section of our article. 2 We note that the context of drug reimbursement differs between the United States and most European countries, including Italy.In the United States, Medicare, which is one of the largest public payers, provides coverage for off-label uses that are supported by Medicare-approved compendia even if these uses have not been reviewed by the US Food and Drug Administration; most other third-party payers have followed suit.One of the authors (A.A.P.) of our article has described some of the challenges related to this policy and the fact that there is a need for both better evidence and processes for assessing the evidence of cancer drugs. 3 We recognize that there cannot always be a new trial to explore every off-label use, and our guidance may not be applicable for every clinical application.However,weareconfidentthat,iffuturetrialsofoff-labeluses were designed with our effectiveness guidance document in mind, the results would be more informative and meaningful to patients, prescribers, payers, and policy makers.Meanwhile, as the letter of Perrone et al 1 documents, evidence development in cancer cannot only focus on randomized controlled trials.Multiple evidence sources, continuous aggregating data, and disciplined iterative evaluation must be parts of our ethos to allow for more informed decision making.This approach to continuous learning is exactly the premise behind learning health care approaches, and off-label oncology is the exemplar use case. 4
Abstract 454: Glucocorticoids enhance metastatsis and tumorigenicity in a triple negative breast cancer cell line
Authors: Yen-Shen Lu, Ming Gao, Pei-Fang Wu, Ching-Hung Lin, Ling-Chun Yeh, Chun-Wei Chen, Ann-Lii Cheng
Journal: Cancer Research (2012)

Abstract Glucocorticoid (GC) is commonly co-administered with chemotherapy to prevent drug-induced allergic reaction, nausea, and vomiting. We have previously reported that GC may affect growth and chemosensitivity of carcinoma cells via diverse mechanisms (Lung Cancer 2006, 53:303-10; J Endocrinol 2006,188:311-9; World J Gastroenterol. 2005, 28:6373-80). Along this line, we further explored the effect of GC on breast cancer cells. Treatment of dexamethasone (DEX) resulted in early axillary lymph node metastases, and increased the number of lung and liver metastases in an orthotopic xenograft model of a triple negative breast cancer cell line (MDA-MB-231) in nude mice (BALB/cAnN.Cg-Foxn1nu/CrlNarl). In tail vein injection assay of cancer metastasis, treatment of DEX dramatically enhanced the lung metastatic potential of a lung-seeking sub-clone, MDA-MB-231-Lu2 (derived from lung metastasis of MDA-MB-231 cells after two in vivo passages in nude mice using intracardiac injection). To explore the mechanism of GC-induced metastasis of breast cancer cells, we performed several in vitro studies. While DEX does not affect the proliferation rate of MDA-MB-231 cells according to MTT assay, treatment of DEX enhanced the tumorigenicity of the cells according to soft agar tumor sphere formation assay. On the other hand, treatment of DEX decreased tumorigenicity in two non-TNBC cell lines, MCF7 and T47D cells. Using quantitative polymerase chain reaction and Western blots assay, we found that treatment of DEX increased the expression of Slug, an epithelial-to-mesenchymal transition (EMT) related gene, and angiopoietin-like 4 (ANGPTL4), an important lung metastasis related gene, in MDA-MB-231 cells, but not in MCF7 and T47D cells. Using transwell migration/invasion assay (with or without matrigel above the membrane), we found that the conditioned medium of DEX-treated lung and liver tissues of mice attracted the MDA-MB-231 cells and promote migration/invasion. In conclusion, GC enhances metastasis and tumorigenicity in MDA-MB-231 cells, a triple negative breast cancer cell line. Whether GC may have a detrimental clinical effect on this subtype of breast cancer patients need to be verified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 454. doi:1538-7445.AM2012-454
Role of Tachycardia as an Inotropic Stimulus in Man
Authors: Donald R. Ricci, Arthur E. Orlick, Edwin L. Alderman, Neil B. Ingels, George T. Daughters, Catherine A. Kusnick, Bruce A. Reitz, Edward B. Stinson
Journal: Journal of Clinical Investigation (1979)

We examined the inotropic effect of tachycardia in nine postsurgical aortocoronary bypass graft patients (with intact cardiac innervation) and nine cardiac allograft recipients (with denervated hearts). The changes in stroke volume (SV) and velocity of circumferential fiber shortening (VCF) which accompany sudden increases and decreases in atrial pacing frequency were determined by computer-aided fluoroscopic analysis of the motion of surgically implanted midwall myocardial markers. Because the first beat after a change in rate retains the frequency characteristics of the preceding rate, we compared the first posttachycardia beat with control beats and late tachycardia beats with the first tachycardia beat; afterload and preload for each pair of beats were similar. For an increase in heart rate of 50 beats/min, SV and VCF rose 79 and 64% from the first tachycardia beat to late tachycardia beats, and SV and VCF rose 8 and 35% from control beats to the first posttachycardia beat in the innervated group. Responses in the denervated group were not significantly different from those in the innervated group. The degree of the inotropic response was positively correlated with the magnitude of the increase in heart rate (r = 0.91). The decay in augmented contractility after decreasing the rate back to control levels fits an exponential relationship with a mean t½ of 1.7 s. Thus, in conscious man, increases in heart rate represent a positive inotropic stimulus, independent of other factors influencing ventricular performance and unaffected by neural innervation, and should be considered when changes in cardiac function are interpreted during serial studies or after drug administration.
Colonic work-up after incomplete colonoscopy: significant new findings during follow-up
Authors: M. Neerincx, J. Terhaar sive Droste, C. Mulder, M. Räkers, J. Bartelsman, R. Loffeld, H. Tuynman, R. Brohet, R. van der Hulst
Journal: Endoscopy (2010)

Background and study aims: Cecal intubation is not achieved in 2 – 23 % of colonoscopies. The efforts made by physicians to visualize the remaining colon and the number of missed significant lesions are unknown. This study evaluates 1) the reasons for incomplete colonoscopy, 2) the rates of complete colonic evaluation after incomplete colonoscopy, and 3) the number of (pre-) malignant lesions missed by incomplete colonoscopy.
Ethnography, cultural context, and assessments of reproductive success matter when discussing human mating strategies
Authors: Agustin Fuentes
Journal: Behavioral and Brain Sciences (2005)

The target article effectively assesses multiple hypotheses for human sexuality, demonstrating support for a complex, integrated perspective. However, care must be taken when extrapolating human universal patterns from specific cultural subsets without appropriate ethnographic contexts. Although it makes a strong contribution to the investigation of human sexuality, the basal reliance on a reductionist perspective constrains the full efficacy of this research.
Role in nude mice of interferon and natural killer cells in inhibiting the tumorigenicity of human hepatocellular carcinoma cells infected with hepatitis B virus
Authors: Daniel Shouval, Bracha Rager-Zisman, Phuc Quan, David A. Shafritz, Barry R. Bloom, Lola M. Reid
Journal: Journal of Clinical Investigation (1983)

The human hepatoma cell line, PLC/PRF/5, which is persistently infected with hepatitis B virus (HBV), has integrated HBV-DNA, secretes HBV surface antigen (HBsAg), and does not grow readily in congenitally athymic (nu/nu) mice. The present investigation was undertaken to ascertain whether the low tumorigenicity of this cell line was governed by a host immune response and/or was related to expression of HBsAg. Subcutaneous injection of 4-5 X 10(6) cells into BALB/c nude mice produced localized encapsulated tumors with morphologic features of primary hepatocellular carcinoma in 25% of the animals within 29-40 d. No tumor growth was observed at lower cell inocula. In contrast, SK-HEP-1, an HBV-negative human hepatoma cell line, produced tumors at 1-5 X 10(6) cells inocula in 66% of the animals. Immunosuppression of mice with antilymphocyte serum (ALS) or irradiation increased tumor incidence in mice inoculated with 1 X 10(6) PLC/PRF/5 cells to almost 100% and produced local invasiveness. Immunosuppression also reduced the latency, i.e., time to tumor appearance, and increased mean tumor weight. These results suggest that tumorigenicity was limited by the host immune response. The nature of the response was delineated by treating nude mice challenged with tumor cells with sheep anti-mouse interferon globulin (anti-IFN). When 2 X 10(6) cells were injected, tumor growth occurred in 75% of anti-IFN-treated mice, whereas controls injected with the same number of cells, but not receiving anti-IFN, failed to develop tumors. The tumors in the anti-IFN-treated mice were highly invasive and the latency period until tumor appearance was reduced to 3-5 d. An inverse correlation was found between susceptibility of the hepatoma cells to natural killer (NK) activity in vitro and resistance to tumor growth in vivo. In vitro cytotoxicity for PLC/PRF/5 cells was eliminated by anti-NK 1.1 and complement, establishing the effector cell as an NK cell. NK cell activity 14 d after inoculation of mice with PLC/PRF/5 cells was augmented against PLC/PRF/5 target cells but not against SK-HEP-1 cells. Treatment of mice with ALS, irradiation, or anti-IFN abolished NK activity against PLC/PRF/5 cells. Co-cultivation of nude mouse spleen cells with PLC/PRF/5 but not with HBsAg or SK-HEP-1 cells induced secretion of murine IFNalpha. These results suggest that the IFN/NK cell system may play a role in limiting tumorigenicity and invasiveness of HBV-infected human hepatocellular carcinoma cells by a mechanism similar to that found for other cells persistently infected with viruses.
Type 2 Diabetes Mellitus Is Associated With Faster Degeneration of Bioprosthetic Valve
Authors: Roberto Lorusso, Sandro Gelsomino, Fabiana Lucà, Giuseppe De Cicco, Giuseppe Billè, Rocco Carella, Emmanuel Villa, Gianni Troise, Mario Viganò, Carlo Banfi, Carmine Gazzaruso, Pier Gagliardotto, Lorenzo Menicanti, Francesco Formica, Giovanni Paolini, Stefano Benussi, Ottavio Alfieri, Matteo Pastore, Sandro Ferrarese, Giovanni Mariscalco, Germano Di Credico, Cristian Leva, Claudio Russo, Aldo Cannata, Roberto Trevisan, Ugolino Livi, Roberto Scrofani, Carlo Antona, Andrea Sala, Gian Franco Gensini, Jos Maessen, Andrea Giustina
Journal: Circulation (2011)

Background— The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. Methods and Results— Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score–matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM ( P &lt;0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6–85.5] versus 95.4% [95% confidence interval, 83.9–100], P &lt;0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28–3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable. Conclusions— Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.
Increased Cerebral Cannabinoid-1 Receptor Availability Is a Stable Feature of Functional Dyspepsia: A [18F]MK-9470 PET Study
Authors: Huynh Giao Ly, Jenny Ceccarini, Nathalie Weltens, Guy Bormans, Koen Van Laere, Jan Tack, Lukas Van Oudenhove
Journal: Psychotherapy and Psychosomatics (2015)

Background: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved. The authors aimed to assess and compare in vivo cerebral cannabinoid-1 (CB1) receptor availability between FD patients and age-, gender- and BMI-matched healthy controls (HC). Methods: Twelve FD patients and 12 matched HC were investigated using positron emission tomography (PET) with the CB1 receptor radioligand [18F]MK-9470. Nine of the patients received a second PET scan after a naturalistic follow-up period of 36 ± 9.6 months (range: 25.2-50.4 months). Results: FD patients had significantly higher CB1 receptor availability in the cerebral regions involved in (visceral) nociception (brainstem, insula, anterior cingulate cortex) as well as in the homeostatic and hedonic regulation of food intake [hypothalamus, (ventral) striatum] (p &lt; 0.05 corrected for multiple testing, region of interest analysis), which persisted after a follow-up period of 36 ± 9.6 months. Conclusions: Although these findings need replication in larger samples, they suggest that the abnormal brain activity in several of these regions, previously demonstrated in FD, may be due to a sustained endocannabinoid system dysfunction, identifying it as a potential novel target for treatment and warranting further studies to elucidate whether it is also a feature of other FGIDs or FSSs.
Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) results in the release of functional soluble TRAIL/Apo-2L
Authors: Troy J. Kemp, Aaron T. Ludwig, James K. Earel, Jill M. Moore, Rebecca L. VanOosten, Bonita Moses, Kevin Leidal, William M. Nauseef, Thomas S. Griffith
Journal: Blood (2005)
A new settlement for health and social care?
Authors: S. Iliffe, J. Manthorpe
Journal: BMJ (2014)

Alignment, adequacy, and affordability provide its analytical framework

A story currently circulating in English social services tells how, at the end of the world, there will be four living organisms left on our planet. Two will be cockroaches and the other two will be trying to integrate health and social care. Despite this weary practitioner view, politicians and managers see integration as the solution to the underperformance of both the NHS and local government in the care of older people with complex needs. The King’s Fund has now published the interim report of the Commission on the Future of the Health and Social Care in England (the Barker report), A New Settlement for Health and Social Care .1 It opens with a discussion of the history of relations between health and social services, makes a plea for “better integration,” and warns of “hard choices” ahead.

While the history is a useful corrective to professional and public ignorance about how health and social care have evolved, the Barker report has little to add about the mechanisms of integration across disciplines, sectors, and agencies. There is a paucity of robust systematic reviews or peer …
Molecular composition of Ro small ribonucleoprotein complexes in human cells. Intracellular localization of the 60- and 52-kD proteins.
Authors: A Kelekar, M R Saitta, J D Keene
Journal: Journal of Clinical Investigation (1994)

Ro small ribonucleoprotein complexes (RoRNPs) are thought to comprise several proteins, including the 60-kD Ro and the 52-kD Ro proteins, and several small RNAs, designated Y RNAs. Although RoRNPs are fairly ubiquitous in nature, their precise composition remains unknown, their function has been elusive, and their intracellular localization has been controversial. We have analyzed HeLa cell extracts by glycerol density gradient fractionation in order to determine the distribution of the individual protein and RNA components of RoRNPs. We found that 52-kD Ro was not detectable in an RNP complex with the 60-kD protein under a variety of conditions. Pretreatment of cell extracts with ribonuclease affected gradient migration of the 60-kD but not the 52-kD protein, suggesting that the latter is not complexed with RNA. The migration of the hY RNAs in these gradients closely followed that of 60-kD and not 52-kD Ro. Immunofluorescence analysis of two different cell lines with monospecific antibodies against 52- and 60-kD proteins strongly suggests that these two proteins are not present on overlapping sets of structures in vivo. We conclude that the 52-kD Ro protein is not a detectable component of the RoRNP complex under these conditions despite its reactivity with Ro autoimmune antisera.