Methods for the guideline-based development of quality indicators--a systematic review

<p>Abstract</p> <p>Background</p> <p>Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.</p> <p>Methods</p> <p>We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.</p> <p>Results</p> <p>From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.</p> <p>Conclusions</p> <p>Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.</p

Rate-dependent Ca2+ signalling underlying the force-frequency response in rat ventricular myocytes: A coupled electromechanical modeling study

Rate-dependent effects on the Ca2+ sub-system in a rat ventricular myocyte are investigated. Here, we employ a deterministic mathematical model describing various Ca2+ signalling pathways under voltage clamp (VC) conditions, to better understand the important role of calmodulin (CaM) in modulating the key control variables Ca2+/calmodulin-dependent protein kinase-II (CaMKII), calcineurin (CaN), and cyclic adenosine monophosphate (cAMP) as they affect various intracellular targets. In particular, we study the frequency dependence of the peak force generated by the myofilaments, the force-frequency response (FFR). Our cell model incorporates frequency-dependent CaM-mediated spatially heterogenous interaction of CaMKII and CaN with their principal targets (dihydropyridine (DHPR) and ryanodine (RyR) receptors and the SERCA pump). It also accounts for the rate-dependent effects of phospholamban (PLB) on the SERCA pump; the rate-dependent role of cAMP in up-regulation of the L-type Ca2+ channel (ICa;L); and the enhancement in SERCA pump activity via phosphorylation of PLB.Our model reproduces positive peak FFR observed in rat ventricular myocytes during voltage-clamp studies both in the presence/absence of cAMP mediated -adrenergic stimulation. This study provides quantitative insight into the rate-dependence of Ca2+-induced Ca2+-release (CICR) by investigating the frequency-dependence of the trigger current (ICa;L) and RyR-release. It also highlights the relative role of the sodium-calcium exchanger (NCX) and the SERCA pump at higher frequencies, as well as the rate-dependence of sarcoplasmic reticulum (SR) Ca2+ content. A rigorous Ca2+ balance imposed on our investigation of these Ca2+ signalling pathways clarifies their individual roles. Here, we present a coupled electromechanical study emphasizing the rate-dependence of isometric force developed and also investigate the temperature-dependence of FFR. Our model provides mechanistic biophysically based explanations for the rate-dependence of CICR, generating useful and testable hypotheses. Although rat ventricular myocytes exhibit a positive peak FFR in the presence/absence of beta-adrenergic stimulation, they show a characteristic increase in the positive slope in FFR due to the presence of Norepinephrine or Isoproterenol. Our study identifies cAMP-mediated stimulation, and rate-dependent CaMKII-mediated up-regulation of ICa;L as the key mechanisms underlying the aforementioned positive FFR

A Fluorescent Glycolipid-Binding Peptide Probe Traces Cholesterol Dependent Microdomain-Derived Trafficking Pathways

10.1371/journal.pone.0002933PLoS ONE38

Simulating the evolution of Hardangerjøkulen ice cap in southern Norway since the mid-Holocene and its sensitivity to climate change

Understanding of long-term dynamics of glaciers and ice caps is vital to assess their recent and future changes, yet few long-term reconstructions using ice flow models exist. Here we present simulations of the maritime Hardangerjøkulen ice cap in Norway from the mid-Holocene through the Little Ice Age (LIA) to the present day, using a numerical ice flow model combined with glacier and climate reconstructions. In our simulation, under a linear climate forcing, we find that Hardangerjøkulen grows from ice-free conditions in the mid-Holocene to its maximum extent during the LIA in a nonlinear, spatially asynchronous fashion. During its fastest stage of growth (2300-1300 BP), the ice cap triples its volume in less than 1000 years. The modeled ice cap extent and outlet glacier length changes from the LIA until today agree well with available observations. Volume and area for Hardangerjøkulen and several of its outlet glaciers vary out-of-phase for several centuries during the Holocene. This volume-area disequilibrium varies in time and from one outlet glacier to the next, illustrating that linear relations between ice extent, volume and glacier proxy records, as generally used in paleoclimatic reconstructions, have only limited validity. We also show that the present-day ice cap is highly sensitive to surface mass balance changes and that the effect of the ice cap hypsometry on the mass balance- altitude feedback is essential to this sensitivity. A mass balance shift by +0.5m w.e. relative to the mass balance from the last decades almost doubles ice volume, while a decrease of 0.2 mw.e. or more induces a strong mass balance-altitude feedback and makes Hardangerjøkulen disappear entirely. Furthermore, once disappeared, an additional +0.1m w.e. relative to the present mass balance is needed to regrow the ice cap to its present-day extent. We expect that other ice caps with comparable geometry in, for example, Norway, Iceland, Patagonia and peripheral Greenland may behave similarly, making them particularly vulnerable to climate change

Glacier change: Dynamic projections

Mountain glaciers around the world are in decay. According to a modelling study that — unusually — includes full ice flow physics, those in Western Canada will largely be restricted to the coastal region by the year 2100

Mass Balance

This chapter reviews key approaches used to determine the mass balance of valley glaciers, ice caps and ice sheets and monitor their mass changes over time. The methods discussed include in situ, satellite/airborne and gravimetric observations, and modelling driven by outputs from climate models. The chapter describes their specific application to valley glaciers and ice caps, the Antarctic Ice Sheet and the Greenland Ice Sheet, and the corresponding spatial and temporal mass-balance variations found over the past few decades