Does facilitated Advance Care Planning reduce the costs of care near the end of life? Systematic review and ethical considerations

Background: While there is increasing evidence that Advance Care Planning has the potential to strengthen patient autonomy and improve quality of care near the end of life, it remains unclear whether it could also reduce net costs of care. Aim: This study aims to describe the cost implications of Advance Care Planning programmes and discusses ethical conflicts arising in this context. Design: We conducted a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources: We systematically searched the databases PubMed, NHS EED, EURONHEED, Cochrane Library and EconLit. We included empirical studies (no limitation to study type) that investigated the cost implications of Advance Care Planning programmes involving professionally facilitated end-of-life discussions. Results and discussion: Seven studies met our inclusion criteria. Four of them used a randomised controlled design, one used a before-after design and two were observational studies. Six studies found reductions in costs of care ranging from USD1041 to USD64,827 per patient, depending on the study period and the cost measurement. One study detected no differences in costs. Studies varied considerably regarding the Advance Care Planning intervention, patient selection and costs measured which may explain some of the variations in findings. Normative appraisal: Looking at the impact of Advance Care Planning on costs raises delicate ethical issues. Given the increasing pressure to reduce expenditures, there may be concerns that cost considerations could unduly influence the sensitive communication process, thus jeopardising patient autonomy. Safeguards are proposed to reduce these risks. Conclusion: The limited data indicate net cost savings may be realised with Advance Care Planning. Methodologically robust trials with clearly defined Advance Care Planning interventions are needed to make the costs and returns of Advance Care Planning transparent

“Brown‐Ring”‐Related Coordination Polymers of the Quartet‐{FeNO}7 Chromophore

A conspicuous detail of the so‐called brown‐ring test (the analytical test on nitrate) is the reddish color of the bottom layer of concentrated sulfuric acid, which develops upon the bleeding of the brown layer into the acid. Crystals of the same color form from a solution of ferrous sulfate in concentrated sulfuric acid on saturation with gaseous nitric oxide. The structure of this H3O[{Fe(NO)(μ4‐SO4)(μ2‐SO4)0.5}n/n] (1a) is made up from infinite chessboard‐type layers with sulfur on the field junctions and Fe(NO) moieties below the black and above the white fields. An Fe–N–O angle of about 160° causes disorder in the tetragonal space group I4/mmm. A similar crystal pathology was found in the related [{Fe(MeOH)(NO)(μ4‐SO4)}n/n] (1b) in the same crystal class. A one‐dimensional coordination polymer is formed in crystals of a third compound that comprises the Fe(NO)O5 coordination pattern, namely the brown oxalato species [{Fe(H2O)(NO)(μ2‐ox)}n/n·H2O] (2). A still larger NO tilt of about 156° is not obscured by disorder in the triclinic crystals of 2

Use of high-plex data reveals novel insights into the tumour microenvironment of clear cell renal cell carcinoma

This work was supported by Medical Research Scotland (MRS), NHS Lothian, NanoStringTechnologies, and the Industrial Centre for AI Research in Digital Diagnostics (iCAIRD) which is funded by Innovate UK on behalf of UK Research and Innovation (UKRI) [project number: 104690].Although Immune Checkpoint Inhibitors (ICIs) have significantly improved the oncological outcomes, about one third of patients affected by Clear Cell Renal Cell Carcinoma (ccRCC) still experience recurrence. Current prognostic algorithms like the Leibovich Score (LS) rely on morphological features manually assessed by pathologists, and are therefore subject to bias. Moreover, these tools do not consider the heterogeneous molecular milieu present in the Tumour Microenvironment (TME), which may have prognostic value. We systematically developed a semi-automated method to investigate 62 markers and their combinations in 150 primary ccRCCs using multiplex Immunofluorescence (mIF), NanoString GeoMx® Digital Spatial Profiling (DSP) and Artificial Intelligence (AI)-assisted image analysis in order to find novel prognostic signatures and investigate their spatial relationship. We found that coexpression of Cancer Stem Cell (CSC) and Epithelial-to-Mesenchymal Transition (EMT) markers such as OCT4 and ZEB1 are indicative of poor outcome. OCT4 and the immune markers CD8, CD34 and CD163 significantly stratified patients at intermediate LS. Furthermore, augmenting the LS with OCT4 and CD34 improved patient stratification by outcome. Our results support the hypothesis that combining molecular markers has prognostic value and can be integrated with morphological features to improve risk stratification and personalised therapy. To conclude, GeoMx® DSP and AI image analysis are complementary tools providing high multiplexing capability required to investigate the TME of ccRCC, while reducing observer bias.Publisher PDFPeer reviewe

Quasi-classical path integral approach to supersymmetric quantum mechanics

{}From Feynman's path integral, we derive quasi-classical quantization rules in supersymmetric quantum mechanics (SUSY-QM). First, we derive a SUSY counterpart of Gutzwiller's formula, from which we obtain the quantization rule of Comtet, Bandrauk and Campbell when SUSY is good. When SUSY is broken, we arrive at a new quantization formula, which is found as good as and even sometime better than the WKB formula in evaluating energy spectra for certain one-dimensional bound state problems. The wave functions in the stationary phase approximation are also derived for SUSY and broken SUSY cases. Insofar as a broken SUSY case is concerned, there are strong indications that the new quasi-classical approximation formula always overestimates the energy eigenvalues while WKB always underestimates.Comment: 13 pages + 5 figures, complete paper submitted as postscript file, to appear in Phys. Rev.

Tachyon search speeds up retrieval of similar sequences by several orders of magnitude

Summary: The usage of current sequence search tools becomes increasingly slower as databases of protein sequences continue to grow exponentially. Tachyon, a new algorithm that identifies closely related protein sequences ~200 times faster than standard BLAST, circumvents this limitation with a reduced database and oligopeptide matching heuristic

A complex regional intervention to implement advance care planning in one town's nursing homes: Protocol of a controlled inter-regional study

<p>Abstract</p> <p>Background</p> <p>Advance Care Planning (ACP) is an emerging strategy to ensure that well-reflected, meaningful and clearly documented treatment preferences are available and respected when critical decisions about life-sustaining treatment need to be made for patients unable to consent. In Germany, recent legislation confirms that advance directives (AD) have to be followed if they apply to the medical situation, but implementation of ACP has not yet been described.</p> <p>Methods/Design</p> <p>In a longitudinal controlled study, we compare 1 intervention region (4 nursing homes [n/hs], altogether 421 residents) with 2 control regions (10 n/hs, altogether 985 residents). Inclusion went from 01.02.09 to 30.06.09, observation lasted until 30.06.10. Primary endpoint is the prevalence of ADs at follow-up, 17 (12) months after the first (last) possible inclusion. Secondary endpoints compare relevance and validity of ADs, process quality, the rate of life-sustaining interventions and, in deceased residents, location of death and intensity of treatment before death. The regional multifaceted intervention on the basis of the US program Respecting Choices^®comprises training of n/h staff as facilitators, training of General Practitioners, education of hospital and ambulance staff, and development of eligible tools, including Physician Orders for Life-Sustaining Treatment in case of Emergency (POLST-E).</p> <p><it>Participation data: </it>Of 1406 residents reported to live in the 14 n/hs plus an estimated turnover of 176 residents until the last possible inclusion date, 645 (41%) were willing to participate. Response rates were 38% in the intervention region and 42% in the control region. Non-responder analysis shows an equal distribution of sex and age but a bias towards dependency on nursing care in the responder group. <it>Outcome analysis </it>of this study will become available in the course of 2011.</p> <p>Discussion</p> <p>Implementing an ACP program for the n/hs and related health care providers of a region requires a complex community intervention with the effect of nothing less than a cultural shift in this health care sector. This study is to our knowledge the first to develop a strategy for regional implementation of ACP, and to evaluate its feasibility in a controlled design.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN99887420">ISRCTN99887420</a></p