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This chapter considers how innovation policy and health law – including food and drug regulation, healthcare reimbursement, and direct R&D subsidies – have both encouraged and impeded the development and allocation of new technologies in the fight against COVID-19. First, an expansive diagnostic testing program for COVID-19 is critical both to slow the spread of the disease and to ensure that future outbreaks can be detected early. The disastrous US testing response represents both an individual regulatory failure and a failure of coordination among agencies including the Food and Drug Administration (FDA), Centers for Disease Control (CDC), and Centers for Medicare and Medicaid Services (CMS). On the treatment side, drugmakers have rushed to identify new and existing compounds for potential COVID-19 efficacy against the backdrop of potentially lengthy and expensive clinical trials. In response, the FDA has granted Emergency Use Authorizations for several of these drugs, which requires balancing risks and harms on only minimal evidence. The intersection between incentives and regulatory oversight has profoundly shaped the innovation landscape for new COVID-19 treatments, such as by permitting widespread use in ways that do not improve the evidence base about which therapeutics are most effective. Finally, extinguishing COVID-19 will require the development of a broadly effective vaccine. This is an opportunity to develop and implement novel ex post rewards, including reimbursement incentives per vaccination to promote vaccine uptake. Each of these areas reveals important lessons to help policymakers better prepare for the next pandemic.
Medical devices have historically been less regulated than their drug and biologic counterparts. A benefit of this less demanding regulatory regime is facilitating innovation by making new devices available to consumers in a timely fashion. Nevertheless, there is increasing concern that this approach raises serious public health and safety concerns. The Institute of Medicine in 2011 published a critique of the American pathway allowing moderate-risk devices to be brought to the market through the less-rigorous 501(k) pathway, flagging a need for increased postmarket review and surveillance. High-profile recalls of medical devices, such as vaginal mesh products, along with reports globally of nearly two million injuries and more than 80,000 deaths linked to faulty medical devices, have raised public health critiques regarding the oversight of these products. Should we follow the recommendation of the Institute of Medicine to reduce the use of the 510(k) pathway, and, if so, what should replace it? What would an ideal regulatory pathway, reflecting the twin goals of innovation and patient protection, look like in the twenty-first century? These questions are complicated by new tools and mechanisms that can be used to achieve our goals. For example, in an era of big data, where we have the capabilities to better follow postmarket incidents, what should postmarket review look like?
Regulators have been more permissive for medical devices compared to their drug and biologic counterparts. While innovative products can thereby reach consumers more quickly, this approach raises serious public health and safety concerns. Additionally, the nature of medical devices is rapidly changing, as software has become as important as hardware. Regulation must keep pace with the current developments and controversies of this technology. This volume provides a multidisciplinary evaluation of the ethical, legal, and regulatory concerns surrounding medical devices in the US and EU. For medical providers, policymakers, and other stakeholders, the book offers a framework for the opportunities and challenges on the horizon for medical device regulation. Readers will gain a nuanced overview of the latest developments in patient privacy and safety, innovation, and new regulatory laws. This book is also available as Open Access on Cambridge Core.
We use comparable 2005 and 2018 population data to assess threats driving the decline of lion Panthera leo populations, and review information on threats structured by problem tree and root cause analysis. We define 11 threats and rank their severity and prevalence. Two threats emerged as affecting both the number of lion populations and numbers within them: livestock depredation leading to retaliatory killing of lions, and bushmeat poaching leading to prey depletion. Our data do not allow determination of whether any specific threat drives declines faster than others. Of 20 local extirpations, most were associated with armed conflicts as a driver of proximate threats. We discuss the prevalence and severity of proximate threats and their drivers, to identify priorities for more effective conservation of lions, other carnivores and their prey.
Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ~0.1 mm d−1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.
Patients with distributive shock who are unresponsive to traditional vasopressors are commonly considered to have severe distributive shock and are at high mortality risk. Here, we assess the cost-effectiveness of adding angiotensin II to the standard of care (SOC) for severe distributive shock in the US critical care setting from a US payer perspective.
Methods
Short-term mortality outcomes were based on 28-day survival rates from the ATHOS-3 study. Long-term outcomes were extrapolated to lifetime survival using individually estimated life expectancies for survivors. Resource use and adverse event costs were drawn from the published literature. Health outcomes evaluated were lives saved, life-years gained, and quality-adjusted life-years (QALYs) gained using utility estimates for the US adult population weighted for sepsis mortality. Deterministic and probabilistic sensitivity analyses assessed uncertainty around results. We analyzed patients with severe distributive shock from the ATHOS-3 clinical trial.
Results
The addition of angiotensin II to the SOC saved .08 lives at Day 28 compared to SOC alone. The cost per life saved was estimated to be $108,884. The addition of angiotensin II to the SOC was projected to result in a gain of .96 life-years and .66 QALYs. This resulted in an incremental cost-effectiveness ratio of $12,843 per QALY. The probability of angiotensin II being cost-effective at a threshold of $50,000 per QALY was 86 percent.
Conclusions
For treatment of severe distributive shock, angiotensin II is cost-effective at acceptable thresholds.
A theorem of Burgess and Stephenson asserts that in an exchange ring with central idempotents, every maximal left ideal is also a right ideal. The proof uses sheaf-theoretic techniques. In this paper, we give a short elementary proof of this important theorem.
Hospital environmental surfaces are frequently contaminated by microorganisms. However, the causal mechanism of bacterial contamination of the environment as a source of transmission is still debated. This prospective study was performed to characterize the nature of multidrug-resistant organism (MDRO) transmission between the environment and patients using standard microbiological and molecular techniques.
Setting
Prospective cohort study at 2 academic medical centers.
Design
A prospective multicenter study to characterize the nature of bacterial transfer events between patients and environmental surfaces in rooms that previously housed patients with 1 of 4 ‘marker’ MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, and MDR Acinetobacter baumannii. Environmental and patient microbiological samples were obtained on admission into a freshly disinfected inpatient room. Repeat samples from room surfaces and patients were taken on days 3 and 7 and each week the patient stayed in the same room. The bacterial identity, antibiotic susceptibility, and molecular sequences were compared between organisms found in the environment samples and patient sources.
Results
We enrolled 80 patient–room admissions; 9 of these patients (11.3%) were asymptomatically colonized with MDROs at study entry. Hospital room surfaces were contaminated with MDROs despite terminal disinfection in 44 cases (55%). Microbiological Bacterial Transfer events either to the patient, the environment, or both occurred in 12 patient encounters (18.5%) from the microbiologically evaluable cohort.
Conclusions
Microbiological Bacterial Transfer events between patients and the environment were observed in 18.5% of patient encounters and occurred early in the admission. This study suggests that research on prevention methods beyond the standard practice of room disinfection at the end of a patient’s stay is needed to better prevent acquisition of MDROs through the environment.
We present the first dedicated study into the phenomenon of ice sails. These are clean ice structures that protrude from the surface of a small number of debris-covered glaciers and can grow to heights of over 25 m. We draw together what is known about them from the academic/exploration literature and then analyse imagery. We show here that ice sails can develop by one of two mechanisms, both of which require clean ice to become surrounded by debris-covered ice, where the debris layer is shallow enough for the ice beneath it to melt faster than the clean ice. Once formed, ice sails can persist for decades, in an apparently steady state, before debris layer thickening eventually causes a reversal in the relative melt rates and the ice sails decay to merge back with the surrounding glacier surface. We support our image-based analysis with a surface energy-balance model and show that it compares well with available observations from Baltoro Glacier in the Karakoram. A sensitivity analysis of the model is performed and confirms the results from our empirical study that ice sails require a relatively high evaporative heat flux and/or a relatively low sensible heat flux in order to exist.
A new two-volume edition of the sources and major analogues of all the Canterbury Tales prepared by members of the New Chaucer Society. This collection, the first to appear in over half a century, features such additions as a fresh interpretation of Chaucer's sources for the frame of the work, chapters on the sources of the General Prologue and Retractions, and modern English translations of all foreign language texts. Chapters on the individual tales contain an updated survey of the present state of scholarship on their source materials. Several sources and analogues discovered during the past fifty years are found here together for the first time, and some other familiar sources are re-edited from manuscripts closer to Chaucer's copies. Volume I includes chapters on the Frame and the tales of the Reeve, Cook, Friar, Clerk, Squire, Franklin, Pardoner, Melibee, Monk, Nun's Priest, Second Nun and Parson. Chapters on the other tales, together with the General Prologue and Retractions will appear in Volume Two. ROBERT M. CORREALE teaches at Wright State University, Ohio; MARY HAMEL teaches at Mount St Mary College, Maryland.
In 2014, the first two authors proved an extension to modules of a theorem of Camillo and Yu that an exchange ring has stable range 1 if and only if every regular element is unit-regular. Here, we give a Morita context version of a stronger theorem. The definition of regular elements in a module goes back to Zelmanowitz in 1972, but the notion of a unit-regular element in a module is new. In this paper, we study unit-regular elements and give several characterizations of them in terms of “stable” elements and “lifting” elements. Along the way, we give natural extensions to the module case of many results about unit-regular rings. The paper concludes with a discussion of when the endomorphism ring of a unit-regular module is a unit-regular ring.