Why is the UK subscription model for antibiotics considered successful?

Commen

Prospective, Randomized, Controlled Trial of Tissue Adhesive (2-Octylcyanoacrylate) vs Standard Wound Closure Techniques for Laceration Repair

Objective: To compare a new tissue adhesive, 2-octylcyanoacrylate, with standard wound closure techniques for the repair of traumatic lacerations. Methods: A prospective, randomized, controlled clinical trial enrolled consecutive patients >1 year of age with non-bite, non-crush-induced lacerations who presented 3 months) was assessed by physicians using a previously validated categorical cosmetic scale and by patients using a 100-mm visual analog scale. Results : There were 63 patients randomized to the octylcyanoacrylate group and 61 patients treated with standard wound closure techniques. The 2 treatment groups were similar with respect to age, gender, race, medical history, and wound characteristics. At the 5-to-10-day follow-up, only 1 wound was infected and only 2 wounds required reclosure due to dehiscence. These 3 patients received treatment with octylcyanoacrylate. At long-term follow-up, the cosmetic appearances were similar according to the patients (octylcyanoacrylate, 83.8 ± 19.4 mm vs standard techniques, 82.5 ± 17.6 mm; p = 0.72) and the physicians (optimal cosmetic appearance, 77% vs 80%; p = 0.67). Conclusions: Wounds treated with octylcyanoacrylate and standard wound closure techniques have similar cosmetic appearances 3 months later.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75580/1/j.1553-2712.1998.tb02590.x.pd

NIMble innovation — a networked model for public antibiotic trials

Antibiotic research and development is at an inflection point. Faced with ongoing problems with commercial innovation, we argue for a networked public approach to support and coordinate existing research and development initiatives by sustainably moving promising compounds through clinical trials. We propose a global public infrastructure of institutes tasked with (1) conducting all trial stages up to market authorisation, including small-scale compound production; (2) negotiating licensing agreements for global production and distribution by industry partners; and (3) using public purchasing agreements or subscription models to ensure commercially viable drug production at equitable prices. We invite stakeholders to consider our Networked Institute Model's benefits for unblocking the public and private antibiotic pipeline

Mean first-passage time of surface-mediated diffusion in spherical domains

We present an exact calculation of the mean first-passage time to a target on the surface of a 2D or 3D spherical domain, for a molecule alternating phases of surface diffusion on the domain boundary and phases of bulk diffusion. The presented approach is based on an integral equation which can be solved analytically. Numerically validated approximation schemes, which provide more tractable expressions of the mean first-passage time are also proposed. In the framework of this minimal model of surface-mediated reactions, we show analytically that the mean reaction time can be minimized as a function of the desorption rate from the surface.Comment: to appear in J. Stat. Phy

Multi-Attribute Tradespace Exploration for Survivability

Multi-Attribute Tradespace Exploration for Survivability is a system design and analysis methodology that incorporates survivability considerations into the tradespace exploration process (i.e., a solution-generating and decision-making framework that applies decision theory to model-based design). During the concept generation phase of tradespace exploration, the methodology applies seventeen empirically validated survivability design principles spanning susceptibility reduction, vulnerability reduction, and resilience enhancement. During subsequent concept evaluation, the methodology adds value-based survivability metrics to traditional architectural evaluation criteria of mission utility and lifecycle cost. Applied to a satellite radar mission, the methodology allowed operational survivability to be statistically evaluated across representative distributions of naturally occurring disturbances in the space environment and for survivability to be incorporated as a decision factor earlier in the design process. Constellations in the illustrative example are shown to be the most survivable, mitigating disturbances architecturally, rather than through additive features.Massachusetts Institute of Technology (Systems Engineering Advancement Research Initiative (SEAri))Massachusetts Institute of Technology. Program on Emerging Technologie

A brown wave of riparian woodland mortality following groundwater declines during the 2012-2019 California drought

As droughts become more frequent and more severe under anthropogenic climate change, water stress due to diminished subsurface supplies may threaten the health and function of semi-arid riparian woodlands, which are assumed to be largely groundwater dependent. To better support the management of riparian woodlands under changing climatic conditions, it is essential to understand the sensitivity of riparian woodlands to depth to groundwater (DTG) across space and time. In this study, we examined six stands of riparian woodland along 28 km of the Santa Clara River in southern California. Combining remote sensing data of fractional land cover, based on spectral mixture analysis, with historical groundwater data, we assessed changes in riparian woodland health in response to DTG during the unprecedented 2012–2019 California drought. We observed a coherent 'brown wave' of tree mortality, characterized by decreases in healthy vegetation cover and increases in dead/woody vegetation cover, which progressed downstream through the Santa Clara River corridor between 2012 and 2016. We also found consistent, significant relationships between DTG and healthy vegetation cover, and separately between DTG and dead/woody vegetation cover, indicating that woodland health deteriorated in a predictable fashion as the water table declined at different sites and different times. Based on these findings, we conclude that the brown wave of vegetation dieback was likely caused by local changes in DTG associated with the propagation of precipitation deficits into a depleted shallow alluvial aquifer. These factors suggest that semi-arid riparian woodlands are strongly dependent on shallow groundwater availability, which is in turn sensitive to climate forcing

A Comparison Between the Teg 6s and Teg 5000 Analyzers to Assess Coagulation in Trauma Patients

BACKGROUND Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE Diagnostic test, level II

Hospitalizations in patients with atrial fibrillation:an analysis from ROCKET AF

AIMS: The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. METHODS AND RESULTS: The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. CONCLUSION: Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization

Improved Standardization of Type II-P Supernovae: Application to an Expanded Sample

In the epoch of precise and accurate cosmology, cross-confirmation using a variety of cosmographic methods is paramount to circumvent systematic uncertainties. Owing to progenitor histories and explosion physics differing from those of Type Ia SNe (SNe Ia), Type II-plateau supernovae (SNe II-P) are unlikely to be affected by evolution in the same way. Based on a new analysis of 17 SNe II-P, and on an improved methodology, we find that SNe II-P are good standardizable candles, almost comparable to SNe Ia. We derive a tight Hubble diagram with a dispersion of 10% in distance, using the simple correlation between luminosity and photospheric velocity introduced by Hamuy & Pinto 2002. We show that the descendent method of Nugent et al. 2006 can be further simplified and that the correction for dust extinction has low statistical impact. We find that our SN sample favors, on average, a very steep dust law with total to selective extinction R_V<2. Such an extinction law has been recently inferred for many SNe Ia. Our results indicate that a distance measurement can be obtained with a single spectrum of a SN II-P during the plateau phase combined with sparse photometric measurements.Comment: ApJ accepted version. Minor change