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We compared sepsis “time zero” and Centers for Medicare and Medicaid Services (CMS) SEP-1 pass rates among 3 abstractors in 3 hospitals. Abstractors agreed on time zero in 29 of 80 (36%) cases. Perceived pass rates ranged from 9 of 80 cases (11%) to 19 of 80 cases (23%). Variability in time zero and perceived pass rates limits the utility of SEP-1 for measuring quality.
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaratumab (Lartruvo®), Eli Lilly & Company Limited, to submit evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the Institute's Single Technology Appraisal. The Peninsula Technology Assessment Group critically reviewed the submitted evidence.
Clinical effectiveness was derived from an open-label, randomized controlled trial, JGDG. The economic analysis was based on a partitioned survival model with a time horizon of 25 years. The perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5 percent per year. The company's evidence was submitted in anticipation that olaratumab would be considered as an alternative to doxorubicin, which has been used as a first-line treatment for advanced STS. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement with the NHS England.
In the company's submission, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus doxorubicin alone were GBP 46,076 (USD 61,403) and GBP 47,127 (USD 62,804) per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of GBP 50,000 (USD 66,632) per QALY gained, applicable to end-of-life treatments, was 0.54. The respective estimates in our analysis were approximately GBP 60,000 (USD 79,959) per QALY gained, and the probability of cost-effectiveness was 0.21. The increase in the ICERs was primarily due to differences in extrapolation of overall survival, and drug administration costs.
Based on the available evidence, olaratumab in combination with doxorubicin improves the survival of patients with advanced STS. However, this treatment is unlikely to be cost-effective. Olaratumab is now recommended for use within the Cancer Drugs Fund.
How does the concept of autonomy assist public responses to ‘lifestyle’ diseases? Autonomy is fundamental to bioethics, but its emphasis on self-determination and individuality hardly supports public health policies to eat and drink less and take more exercise. Autonomy rejects a ‘nanny’ state. Yet, the cost of non-communicable diseases is increasing to individuals personally and to public health systems generally. Health care systems are under mounting and unsustainable pressure. What is the proper responsibility of individuals, governments and corporate interests working within a global trading environment? When public health care resources are unlikely to increase, we cannot afford to be so diffident to the cost of avoidable diseases.
The Supreme Court decision in Montgomery v Lanarkshire ( UKSC11) has been hailed as a landmark not least because the Court enshrines the doctrine of informed consent formally into English law for the first time in relation to medical treatment. This paper explores the decision in Montgomery. It examines what its implications may be in the future for the consent process in relation to health research and innovative treatment and whether it may prove a watershed moment leading to changing dialogues and expectations in relation to consent. First, the paper explores the concept of ‘informed consent’ in clinical research as seen through international, Council of Europe and EU instruments. Second, it considers how English law currently governs the provision of information to research participants in the context of clinical research. It questions whether such an approach will be sustainable in the future. Third, it discusses the decision of the UK Supreme Court in Montgomery v Lanarkshire and asks what might be the impact of this Supreme Court decision in the health research context. It asks whether Montgomery may result in new approaches to consent in health research and innovative treatment.
Pharmacy services are undoubtedly an important part of primary care. Pharmacists are entrepreneurs and simultaneously they are entrusted with a public mission in the health care sector. Pharmacies then reflect a contrast between a commercial/economic objective and public interest, which is to be identified with citizens’ universal right to health care services. This is the reason why in Italy, as in many other EU countries, pharmacies supply their services according to a prior authorisation granted by public authorities. In common with many EU countries, this authorisation is secured according to a demographic criterion. It is only by means of these licensed pharmacies that citizens can buy drugs under medical prescription. Accordingly, the health system is to be driven by public interest, which has yet to prove how competing interests may be regulated in serving health needs. In the light of EU law, the article advocates for an innovative legal and organisational tool whereby to organise the Italian pharmacy system in order to combine economic consideration and public benefit.
This article reviews current trends in patent claims regarding personalised, stratified and precision medicine. These trends are not particularly well understood by policymakers, even less by the public, and are quite recent. Consequently, their implications for the public interest have hardly been thought out. Some see personalised and other secondary drug patent claims as promoting better targeted treatment. Others are inclined to see them as \manifestations of ‘evergreening’ whereby companies are, in some cases quite cynically, trying to extend market monopolies in old products or creating new monopolies based on supposedly improved versions of such earlier drugs. The article claims that the relaxation of ‘novelty’ is a privilege unavailable to inventions in other fields and that on balance the patent system does privilege this industry and that no adequate case has yet been made thus far to prove the public benefits overall.
Regulatory theory is premised on the failure of markets, prompting a focus on regulators and industry from economic perspectives. This article argues that overlooking the public interest in the sustainability of commercial markets risks markets failing completely. This point is exemplified through health care markets – meeting an essential need – and focuses upon innovative medicines as the most desired products in that market. If this seemingly invulnerable market risks failure, there is a pressing need to consider the public interest in sustainable markets within regulatory literature and practice. Innovative medicines are credence goods, meaning that the sustainability of the market fundamentally relies upon the public trusting regulators to vouch for product quality. Yet, quality is being eroded by patent bodies focused on economic benefits from market growth, rather than ensuring innovatory value. Remunerative bodies are not funding medicines relative to market value, and market authorisation bodies are not vouching for robust safety standards or confining market entry to products for ‘unmet medical need’. Arguably, this failure to assure quality heightens the risk of the market failing where it cannot be substituted by the reputation or credibility of providers of goods and/or information such as health care professionals/institutions, patient groups or industry.
The Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project will test the overarching hypothesis that an active hydrological system exists beneath a West Antarctic ice stream that exerts a major control on ice dynamics, and the metabolic and phylogenetic diversity of the microbial community in subglacial water and sediment. WISSARD will explore Subglacial Lake Whillans (SLW, unofficial name) and its outflow toward the grounding line where it is thought to enter the Ross Ice Shelf seawater cavity. Introducing microbial contamination to the subglacial environment during drilling operations could compromise environmental stewardship and the science objectives of the project, consequently we developed a set of tools and procedures to directly address these issues. WISSARD hot water drilling efforts will include a custom water treatment system designed to remove micron and sub-micron sized particles (biotic and abiotic), irradiate the drilling water with germicidal ultraviolet (UV) radiation, and pasteurize the water to reduce the viability of persisting microbial contamination. Our clean access protocols also include methods to reduce microbial contamination on the surfaces of cables/hoses and down-borehole equipment using germicidal UV exposure and chemical disinfection. This paper presents experimental data showing that our protocols will meet expectations established by international agreement between participating Antarctic nations.
We are developing a purely commensal survey experiment for fast (<5 s) transient radio sources. Short-timescale transients are associated with the most energetic and brightest single events in the Universe. Our objective is to cover the enormous volume of transients parameter space made available by ASKAP, with an unprecedented combination of sensitivity and field of view. Fast timescale transients open new vistas on the physics of high brightness temperature emission, extreme states of matter and the physics of strong gravitational fields. In addition, the detection of extragalactic objects affords us an entirely new and extremely sensitive probe on the huge reservoir of baryons present in the IGM. We outline here our approach to the considerable challenge involved in detecting fast transients, particularly the development of hardware fast enough to dedisperse and search the ASKAP data stream at or near real-time rates. Through CRAFT, ASKAP will provide the testbed of many of the key technologies and survey modes proposed for high time resolution science with the SKA.
Chemical constituents trapped within glacial ice provide a unique record of climate, as well as repositories for biological material such as pollen grains, fungal spores, viruses, bacteria and dissolved organic carbon. Past research suggests that the veins of polycrystalline ice may provide a liquid microenvironment for active microbial metabolism fueled by concentrated impurities in the veins. Despite these claims, no direct measurements of impurity concentration in ice veins have been made. Using micro-Raman spectroscopy, we show that sulfate and nitrate concentrations in the veins of glacial ice from Greenland (Greenland Ice Sheet Project 2) and Antarctic (Newall Glacier and a Dominion Range glacier) core samples were 104 and 105 times greater than the concentrations measured in melted (bulk) core water. Methanesulfonate was not found in the veins, consistent with its presence as particulate matter within the ice. The measured vein concentration of molecular anions implies a highly acidic (pH < 3) vein environment with high ionic strength (mM-M). We estimate that the vein volume provides 16.7 and 576 km3 of habitable space within the Greenland and Antarctic ice sheets, respectively, which could support the metabolism of organisms that are capable of growing in cold, high ionic strength solutions with low pH.
We reviewed the effect of 3 interventions to reduce the incidence of intraventricular catheter–related ventriculitis, conducted at a tertiary care center in St Louis, Missouri, during an 8-year period. The incidence density of intraventricular catheter-related ventriculitis decreased substantially after the implementation of standardized management of intraventricular catheters.
Oral morphogenesis in stock 51 of Paramecium tetraurelia was investigated using the techniques of Chatton-Lwoff and protargol silver impregnation. During the stomatogenesis accompanying divisional morphogenesis a new oral anlage field and endoral kinety are formed and persist throughout the interfission period in both the proter and the opisthe. This previously overlooked fact is important for understanding the developmental origins and significance of the endoral kinety and the oral anlage field. Previously, the kinetosomes constituting the oral anlage field were thought to be formed just prior to the onset of stomatogenesis, being in some way derived from the kinetosomes of the endoral kinety. The demonstration of a permanent anlage field as an integral component of the oral assemblage suggests that the earliest stages of stomatogenesis might best be viewed as temporally controlled surfacing and/or ciliation of pre-existing kinetosomes rather than their de novo synthesis. The endoral kinety would thus have no contributory role in the formation of the anlage field used in the immediately ensuing stomatogenesis.
A 65 m vertical shaft was sunk at Dounreay in the 1950s to build a tunnel for the offshore discharge of radioactive effluent from the various nuclear facilities then under construction. In 1959, the Shaft was licensed as a disposal facility for radioactive wastes and was routinely used for the disposal of ILW until 1970. Despite the operation of a hydraulic containment scheme, some radioactivity is known to have leaked into the surrounding rocks. Detailed logging, together with mineralogical and radiochemical analysis of drillcore has revealed four distinct bedding-parallel zones of contamination. The data show that Sr-90 dominates the bulk beta/gamma contamination signal, whereas Cs-137 and Pu-248/249 are found only to be weakly mobile, leading to very low activities and distinct clustering around the Shaft. The data also suggest that all uranium seen in the geosphere is natural in origin. At the smaller scale, contamination adjacent to fracture surfaces is present within a zone of enhanced porosity created by the dissolution of carbonate cements from the Caithness flagstones during long-term rockwater interactions. Quantitative modelling of radionuclide migration, using the multiphysics computer code QPAC shows the importance of different sorption mechanisms and different mineralogical substrates in the Caithnesss flagstones in controlling radionuclide migration.
Pediatric stroke is a rare disorder with a paucity of evidence-based treatment options, and can result in significant morbidity and mortality. In contrast to adult acute ischemic stroke, where the use of recombinant tissue plasminogen activator (rt-PA) has been studied in several large, randomized clinical trials, no high-level evidence exists for the use of thrombolytics in children with stroke. We report a case of a 15-year-old girl who suffered an acute ischemic stroke and had a dramatic improvement in symptoms following the administration of intravenous rt-PA.