Integrating quality into the cycle of therapeutic development

The quality of healthcare, particularly as reflected in current practice versus the available evidence, has become a major focus of national health policy discussions. Key components needed to provide quality care include: 1) development of quality indicators and performance measures from specific practice guidelines, 2) better ways to disseminate such guidelines and measures, and 3) development of support tools to promote standardized practice. Although rational decision-making and development of practice guidelines have relied upon results of randomized trials and outcomes studies, not all questions can be answered by randomized trials, and many treatment decisions necessarily reflect physiology, intuition, and experience when treating individuals. Debate about the role of "evidence-based medicine" also has raised questions about the value of applying trial results in practice, and some skepticism has arisen about whether advocated measures of clinical effectiveness, the basic definition of quality, truly reflect a worthwhile approach to improving medical practice. We provide a perspective on this issue by describing a model that integrates quantitative measurements of quality and performance into the development cycle of existing and future therapeutics. Such a model would serve as a basic approach to cardiovascular medicine that is necessary, but not sufficient, to those wishing to provide the best care for their patients

ACC/AHA Guidelines for Coronary Angiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography)

"The ACC/AHA Task Force on Practice Guidelines herein revises and updates the original “Guidelines for Coronary Angiography,” published in 1987 (1). The frequent and still-growing use of coronary angiography, its relatively high costs, its inherent risks and the ongoing evolution of its indications have given this revision urgency and priority. The expert committee appointed included private practitioners and academicians. Committee members were selected to represent both experts in coronary angiography and senior clinician consultants. Representatives from the family practice and internal medicine professions were also included on the committee. The English-language medical literature was searched for the 10 years preceding development of the guidelines. The searches yielded >1,600 references that the committee reviewed for relevance. Evidence relative to the use of coronary angiography was compiled and evaluated by the committee. Whereas randomized trials are often available for reference in the development of treatment guidelines, randomized trials regarding the use of diagnostic procedures such as coronary angiography are rarely available (2). For development of these guidelines, when coronary angiography was a necessary procedure in describing a clinical subset or in choosing a course of treatment and that therapy was shown to have an advantage for the patient, especially in the context of a randomized trial, then the indication for angiography was given greater consideration than indications cited in less-rigorous evaluations of data.

ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina)

The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Ischemic heart disease is the single leading cause of death in the U.S. The most common manifestation of this disease is chronic stable angina. Recognizing the importance of the management of this common entity and the absence of national clinical practice guidelines in this area, the task force formed the current committee to develop guidelines for the management of patients with stable angina. Because this problem is frequently encountered in the practice of internal medicine, the task force invited the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) to serve as a partner in this effort by naming four general internists to serve on the committee

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function <it>in vivo</it>. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c.</p> <p>Methods</p> <p>In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth.</p> <p>Results</p> <p>These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival.</p> <p>Conclusions</p> <p>We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy.</p

ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery: Executive Summary and Recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery)

The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines was formed to make recommendations regarding the appropriate use of diagnostic tests and therapies for patients with known or suspected cardiovascular disease. Coronary artery bypass graft (CABG) surgery is among the most common operations performed in the world and accounts for more resources expended in cardiovascular medicine than any other single procedure. Since the original Guidelines were published in 1991, there has been considerable evolution in the surgical approach to coronary disease, and at the same time there have been advances in preventive, medical, and percutaneous catheter approaches to therapy. These revised guidelines are based on a computerized search of the English literature since 1989, a manual search of final articles, and expert opinion

Effectiveness of Biodiversity Surrogates for Conservation Planning: Different Measures of Effectiveness Generate a Kaleidoscope of Variation

Conservation planners represent many aspects of biodiversity by using surrogates with spatial distributions readily observed or quantified, but tests of their effectiveness have produced varied and conflicting results. We identified four factors likely to have a strong influence on the apparent effectiveness of surrogates: (1) the choice of surrogate; (2) differences among study regions, which might be large and unquantified (3) the test method, that is, how effectiveness is quantified, and (4) the test features that the surrogates are intended to represent. Analysis of an unusually rich dataset enabled us, for the first time, to disentangle these factors and to compare their individual and interacting influences. Using two data-rich regions, we estimated effectiveness using five alternative methods: two forms of incidental representation, two forms of species accumulation index and irreplaceability correlation, to assess the performance of ‘forest ecosystems’ and ‘environmental units’ as surrogates for six groups of threatened species—the test features—mammals, birds, reptiles, frogs, plants and all of these combined. Four methods tested the effectiveness of the surrogates by selecting areas for conservation of the surrogates then estimating how effective those areas were at representing test features. One method measured the spatial match between conservation priorities for surrogates and test features. For methods that selected conservation areas, we measured effectiveness using two analytical approaches: (1) when representation targets for the surrogates were achieved (incidental representation), or (2) progressively as areas were selected (species accumulation index). We estimated the spatial correlation of conservation priorities using an index known as summed irreplaceability. In general, the effectiveness of surrogates for our taxa (mostly threatened species) was low, although environmental units tended to be more effective than forest ecosystems. The surrogates were most effective for plants and mammals and least effective for frogs and reptiles. The five testing methods differed in their rankings of effectiveness of the two surrogates in relation to different groups of test features. There were differences between study areas in terms of the effectiveness of surrogates for different test feature groups. Overall, the effectiveness of the surrogates was sensitive to all four factors. This indicates the need for caution in generalizing surrogacy tests

1999 Update: ACC/AHA Guidelines for the Management of Patients with Acute Myocardial Infarction: Executive Summary and Recommendations: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)

The American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Management of Patients With Acute Myocardial Infarction have been reviewed over the past 2.5 years since their initial publication in the Journal of the American College of Cardiology (1996;28:1328–1428) to ensure their continued relevancy. The guidelines have been updated to include the most significant advances that have occurred in the management of patients with acute myocardial infarction (AMI) during that time frame. This update was developed to keep the guidelines current without republishing the entire document. This effort represents a new procedure of the ACC/AHA Task Force on Practice Guidelines. These guidelines will be reviewed and updated as necessary until it is deemed appropriate to revise and republish the entire document

1999 Update: ACC/AHA guidelines for the management of patients with acute myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)

The American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Management of Patients With Acute Myocardial Infarction have been reviewed over the past 21/2years since their initial publication (J Am Coll Cardiol 1996;28:1328–428) to ensure their continued relevancy. The guidelines have been updated to include the most significant advances that have occurred in the management of patients with acute myocardial infarction (AMI) during that time frame. This Update was developed to keep the guidelines current without republishing them in their entirety. The Update represents a new procedure of the ACC/AHA Task Force on Practice Guidelines. These guidelines will be reviewed and updated as necessary until it is deemed appropriate to revise and republish the entire document

Phylogenetically and spatially close marine sponges harbour divergent bacterial communities

Recent studies have unravelled the diversity of sponge-associated bacteria that may play essential roles in sponge health and metabolism. Nevertheless, our understanding of this microbiota remains limited to a few host species found in restricted geographical localities, and the extent to which the sponge host determines the composition of its own microbiome remains a matter of debate. We address bacterial abundance and diversity of two temperate marine sponges belonging to the Irciniidae family - Sarcotragus spinosulus and Ircinia variabilis – in the Northeast Atlantic. Epifluorescence microscopy revealed that S. spinosulus hosted significantly more prokaryotic cells than I. variabilis and that prokaryotic abundance in both species was about 4 orders of magnitude higher than in seawater. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) profiles of S. spinosulus and I. variabilis differed markedly from each other – with higher number of ribotypes observed in S. spinosulus – and from those of seawater. Four PCR-DGGE bands, two specific to S. spinosulus, one specific to I. variabilis, and one present in both sponge species, affiliated with an uncultured sponge-specific phylogenetic cluster in the order Acidimicrobiales (Actinobacteria). Two PCR-DGGE bands present exclusively in S. spinosulus fingerprints affiliated with one sponge-specific phylogenetic cluster in the phylum Chloroflexi and with sponge-derived sequences in the order Chromatiales (Gammaproteobacteria), respectively. One Alphaproteobacteria band specific to S. spinosulus was placed in an uncultured sponge-specific phylogenetic cluster with a close relationship to the genus Rhodovulum. Our results confirm the hypothesized host-specific composition of bacterial communities between phylogenetically and spatially close sponge species in the Irciniidae family, with S. spinosulus displaying higher bacterial community diversity and distinctiveness than I. variabilis. These findings suggest a pivotal host-driven effect on the shape of the marine sponge microbiome, bearing implications to our current understanding of the distribution of microbial genetic resources in the marine realm.This work was financed by the Portuguese Foundation for Science and Technology (FCT - http://www.fct.pt) through the research project PTDC/MAR/101431/2008. CCPH has a PhD fellowship granted by FCT (Grant No. SFRH/BD/60873/2009). JRX’s research is funded by a FCT postdoctoral fellowship (grant no. SFRH/BPD/62946/2009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript