Funding models in palliative care: lessons from international experience

Background:Funding models influence provision and development of palliative care services. As palliative care integrates into mainstream health care provision, opportunities to develop funding mechanisms arise. However, little has been reported on what funding models exist or how we can learn from them.Aim:To assess national models and methods for financing and reimbursing palliative care.Design:Initial literature scoping yielded limited evidence on the subject as national policy documents are difficult to identify, access and interpret. We undertook expert consultations to appraise national models of palliative care financing in England, Germany, Hungary, Republic of Ireland, New Zealand, The Netherlands, Norway, Poland, Spain, Sweden, Switzerland, the United States and Wales. These represent different levels of service development and a variety of funding mechanisms.Results:Funding mechanisms reflect country-specific context and local variations in care provision. Patterns emerging include the following:Provider payment is rarely linked to population need and often perpetuates existing inequitable patterns in service provision.Funding is frequently characterised as a mixed system of charitable, public and private payers.The basis on which providers are paid for services rarely reflects individual care input or patient needs.Conclusion:Funding mechanisms need to be well understood and used with caution to ensure best practice and minimise perverse incentives. Before we can conduct cross-national comparisons of costs and impact of palliative care, we need to understand the funding and policy context for palliative care in each country of interest

Perturbation of hyaluronan synthesis in the trabecular meshwork and the effects on outflow facility

PURPOSE. Hyaluronan (HA) is a major component of the aqueous outflow pathway. However, the contribution of HA to human outflow resistance remains unclear. Three HA synthase genes (HAS1-3) have been identified. Here, we evaluate the contribution of each of the HAS proteins to outflow facility in anterior segment perfusion culture. METHODS. Two methods were used to reduce HA synthesis: 1 mM 4-methylumbelliferone (4MU) was used to inhibit all HAS synthases and shRNA silencing lentivirus was generated to knock down expression of each HAS individually. Quantitative RT-PCR, Western immunoblotting and an HA ELISA assay were used to assess HAS mRNA and protein levels and HA concentration, respectively. The effects of 4MU treatment and HAS gene silencing on outflow facility were assessed in human and porcine perfusion culture. RESULTS. Quantitative RT-PCR and Western immunoblotting showed a reduction of each HAS in response to their respective silencing and 4MU treatment. HA concentration was concomitantly reduced. Treatment with 4MU decreased outflow facility in human anterior segments but increased outflow facility in porcine eyes. Lentiviral delivery of HAS1 and HAS2 silencing vectors caused similar opposite effects on outflow facility. Silencing of HAS3 did not significantly affect outflow resistance in either species. CONCLUSIONS. This is the first conclusive evidence for a significant role of HA in the human outflow pathway. HA chains synthesized by HAS1 and HAS2 contribute to outflow resistance, while hyaluronan produced by HAS3 does not appear to play a significant role. (Invest Ophthalmol Vis Sci. 2012;53:4616-4625) DOI:10.1167/iovs.12-9500 H yaluronan (HA) is a large, negatively charged glycosaminoglycan (GAG) chain that is synthesized by three homologous hyaluronan synthase (HAS) enzymes called HAS1, HAS2 and HAS3. 2 The growing HA chain is extruded directly through the plasma membrane into the extracellular milieu. As a result, HA is not sulfated and does not undergo epimerization. Each HAS produces HA in differing amounts and of different sizes: HAS1 produces low amounts of high molecular weight (HMW) HA, HAS2 produces high amounts of HMW HA, while HAS3 produces high amounts of low MW (LMW) HA. 5 The coumarin derivative, 4-methylumbelliferone (4MU), is a potent inhibitor of HA synthesis and exerts its effects two ways: it decreases HAS2 and HAS3 mRNA levels and also depletes the cellular pool of UDP-glucuronic acid, a building block of HA chains. 6 Subsequent studies suggest that 4MU also decreases HAS1 mRNA levels. 7 Previous studies have shown that HASs are expressed by bovine trabecular meshwork cells and in primate trabecular meshwork tissue. 10 HA distribution in the TM has been assessed using HA binding protein (HAbp). HA was found in the anterior non-filtering portion of the TM and in the juxtacanalicular (JCT) or cribriform region near the inner wall of Schlemm's canal. 14,18 As humans age, there is a decrease in the amount of HA and there is a much greater loss in primary open-angle glaucoma (POAG) TM. 12 Experiments performed in the 1950's demonstrated that treatment of bovine eyes with hyaluronidase to degrade HA decreased outflow resistance and consequently increased outflow facility. Recently, we showed that RNAi silencing of versican, an HA binding protein, reduced outflow facility in human anterior segment perfusion culture

Funding models in palliative care: Lessons from international experience

Background: Funding models influence provision and development of palliative care services. As palliative care integrates into mainstream health care provision, opportunities to develop funding mechanisms arise. However, little has been reported on what funding models exist or how we can learn from them. Aim: To assess national models and methods for financing and reimbursing palliative care. Design: Initial literature scoping yielded limited evidence on the subject as national policy documents are difficult to identify, access and interpret. We undertook expert consultations to appraise national models of palliative care financing in England, Germany, Hungary, Republic of Ireland, New Zealand, The Netherlands, Norway, Poland, Spain, Sweden, Switzerland, the United States and Wales. These represent different levels of service development and a variety of funding mechanisms. Results: Funding mechanisms reflect country-specific context and local variations in care provision. Patterns emerging include the following: Provider payment is rarely linked to population need and often perpetuates existing inequitable patterns in service provision. Funding is frequently characterised as a mixed system of charitable, public and private payers. The basis on which providers are paid for services rarely reflects individual care input or patient needs. Conclusion: Funding mechanisms need to be well understood and used with caution to ensure best practice and minimise perverse incentives. Before we can conduct cross-national comparisons of costs and impact of palliative care, we need to understand the funding and policy context for palliative care in each country of interest

Role of Emergency Laparoscopic Colectomy for Colorectal Cancer: A Population-based Study in England.

OBJECTIVE: To evaluate factors associated with the use of laparoscopic surgery and the associated postoperative outcomes for urgent or emergency resection of colorectal cancer in the English National Health Service. SUMMARY OF BACKGROUND DATA: Laparoscopy is increasingly used for elective colorectal cancer surgery, but uptake has been limited in the emergency setting. METHODS: Patients recorded in the National Bowel Cancer Audit who underwent urgent or emergency colorectal cancer resection between April 2010 and March 2016 were included. A multivariable multilevel logistic regression model was used to estimate odds ratios (ORs) of undergoing laparoscopic resection and postoperative outcome according to approach. RESULTS: There were 15,516 patients included. Laparoscopy use doubled from 15.1% in 2010 to 30.2% in 2016. Laparoscopy was less common in patients with poorer physical status [American Society of Anaesthesiologists (ASA) 4/5 vs 1, OR 0.29 (95% confidence interval, 95% CI 0.23-0.37), P < 0.001] and more advanced T-stage [T4 vs T0-T2, OR 0.28 (0.23-0.34), P < 0.001] and M-stage [M1 vs M0, OR 0.85 (0.75-0.96), P < 0.001]. Age, socioeconomic deprivation, nodal stage, hospital volume, and a dedicated colorectal emergency service were not associated with laparoscopy. Laparoscopic patients had a shorter length of stay [median 8 days (interquartile range (IQR) 5 to 15) vs 12 (IQR 8 to 21), adjusted mean difference -3.67 (-4.60 to 2.74), P < 0.001], and lower 90-day mortality [8.1% vs 13.0%; adjusted OR 0.78 (0.66-0.91), P = 0.004] than patients undergoing open resection. There was no significant difference in rates of readmission or reoperation by approach. CONCLUSION: The use of laparoscopic approach in the emergency resection of colorectal cancer is linked to a shorter length of hospital stay and reduced postoperative mortality

Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p<0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p<0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets

Have we seen the geneticisation of society? Expectations and evidence

Abby Lippman’s geneticization thesis, of the early 1990s, argued and anticipated that with the rise of genetics, increasing areas of social and health related activities would come to be understood and defined in genetic terms leading to major changes in society, medicine and health care. We review the considerable literature on geneticization and consider how the concept stands both theoretically and empirically across scientific, clinical, popular and lay discourse and practice. Social science scholarship indicates that relatively little of the original claim of the geneticization thesis has been realised, highlighting the development of more complex and dynamic accounts of disease in scientific discourse and the complexity of relationships between bioscientific, clinical and lay understandings. This scholarship represents a shift in social science understandings of the processes of sociotechnical change, which have moved from rather simplistic linear models to an appreciation of disease categories as multiply understood. Despite these shifts, we argue that a genetic imaginary persists, which plays a performative role in driving investments in new gene-based developments. Understanding the enduring power of this genetic imaginary and its consequences remains a key task for the social sciences, one which treats ongoing genetic expectations and predictions in a sceptical yet open way

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV