Inhaled hypertonic saline acutely increases mucociliary clearance and, in short-term trials, improves lung function in people with cystic fibrosis. We tested the safety and efficacy of inhaled ...hypertonic saline in a long-term trial.
In this double-blind, parallel-group trial, 164 patients with stable cystic fibrosis who were at least six years old were randomly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent (control) saline twice daily for 48 weeks, with quinine sulfate (0.25 mg per milliliter) added to each solution to mask the taste. A bronchodilator was given before each dose, and other standard therapies were continued during the trial.
The primary outcome measure, the rate of change (slope) in lung function (reflected by the forced vital capacity FVC, forced expiratory volume in one second FEV1, and forced expiratory flow at 25 to 75 percent of FVC FEF25-75) during the 48 weeks of treatment, did not differ significantly between groups (P=0.79). However, the absolute difference in lung function between groups was significant (P=0.03) when averaged across all post-randomization visits in the 48-week treatment period. As compared with the control group, the hypertonic-saline group had significantly higher FVC (by 82 ml; 95 percent confidence interval, 12 to 153) and FEV1 (by 68 ml; 95 percent confidence interval, 3 to 132) values, but similar FEF25-75 values. The hypertonic-saline group also had significantly fewer pulmonary exacerbations (relative reduction, 56 percent; P=0.02) and a significantly higher percentage of patients without exacerbations (76 percent, as compared with 62 percent in the control group; P=0.03). Hypertonic saline was not associated with worsening bacterial infection or inflammation.
Hypertonic saline preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with cystic fibrosis. (ClinicalTrials.gov number, NCT00271310.)
True penicillin allergy is rare and is commonly incorrectly reported. In fact, less than five percent of patients who report a penicillin allergy will have a currently active clinically-significant ...IgE- or T-cell-mediated hypersensitivity when appropriately tested. Penicillin is the agent of choice for intrapartum antibiotic prophylaxis to reduce the risk of group B streptococcus early-onset disease in the newborn. Inaccurate penicillin allergy status may lead to inappropriate antibiotic use, as most alternative drugs are more expensive and broader spectrum than penicillin. Penicillin allergy testing has been found to be safe in pregnancy and cost-effective in other patient populations.
To evaluate the cost-effectiveness of penicillin allergy testing and appropriate antibiotic treatment (test then treat strategy) compared to usual care among pregnant women.
We developed a decision tree to evaluate the cost of providing appropriate care via a test then treat strategy for pregnant women who report a penicillin allergy, compared to usual care.
Using the test then treat strategy the additional cost to ensure appropriate care for all pregnant women who report a penicillin allergy, was $1122.38 per person. Adopting a test then treat strategy increased the number of appropriate antibiotic use from 7,843/10,000 to 10,000/10,000 simulations.
Our results show that a test then treat strategy for pregnant women who report a penicillin allergy is a good-value intervention.
Conformational changes caused by adsorption can dramatically affect a molecule’s properties. Despite extensive study, however, the exact mechanisms underpinning conformational switching are often ...unclear. Here we show that the conformation of a prototypical flexible molecule, the free-base tetra(4-bromophenyl) porphyrin, adsorbed on Cu(111), depends critically on its precise adsorption site and that, remarkably, large conformational changes are dominated by van der Waals interactions between the molecule and the substrate surface. A combination of scanning probe microscopy, single-molecule manipulation, DFT with dispersion density functional theory, and molecular dynamics simulations show that van der Waals forces drive significant distortions of the molecular architecture so that the porphyrin can adopt one of two low-energy conformations. We find that adsorption driven by van der Waals forces alone is capable of causing large shifts in the molecular density of states, despite the apparent absence of chemical interactions. These findings highlight the essential role that van der Waals forces play in determining key molecular properties.
High-energy gamma-ray emission from supernova remnants (SNRs) has provided a unique perspective for studies of Galactic cosmic-ray acceleration. Tycho's SNR is a particularly good target because it ...is a young, type Ia SNR that has been well-studied over a wide range of energies and located in a relatively clean environment. Since the detection of gamma-ray emission from Tycho's SNR by VERITAS and Fermi-LAT, there have been several theoretical models proposed to explain its broadband emission and high-energy morphology. We report on an update to the gamma-ray measurements of Tycho's SNR with 147 hr of VERITAS and 84 months of Fermi-LAT observations, which represent about a factor of two increase in exposure over previously published data. About half of the VERITAS data benefited from a camera upgrade, which has made it possible to extend the TeV measurements toward lower energies. The TeV spectral index measured by VERITAS is consistent with previous results, but the expanded energy range softens a straight power-law fit. At energies higher than 400 GeV, the power-law index is 2.92 0.42stat 0.20sys. It is also softer than the spectral index in the GeV energy range, 2.14 0.09stat 0.02sys, measured in this study using Fermi-LAT data. The centroid position of the gamma-ray emission is coincident with the center of the remnant, as well as with the centroid measurement of Fermi-LAT above 1 GeV. The results are consistent with an SNR shell origin of the emission, as many models assume. The updated spectrum points to a lower maximum particle energy than has been suggested previously.
The evolution and compositional structure of the lunar mantle has been extensively modeled but insufficiently constrained by observations. Here, we identify and characterize mantle materials exposed ...by the Moon's largest impact basin to better understand the composition, stratigraphy, and evolution of the upper mantle. The vast South Pole-Aitken Basin (SPA) exhibits a broad, crescent-shaped thorium and potassium distribution. These incompatible elements are predicted to be concentrated in the dregs of the lunar magma ocean during end-stage crystallization. Through consideration of basin formation models convolved with subsequent geologic evolution, we demonstrate that the distribution and implied stratigraphy of Th- and K-bearing materials across SPA are consistent with an upper mantle ejecta origin. The most pristine exposures of these materials are confined to northwest SPA and also exhibit elevated Ti and Fe (relative to the farside highlands) in association with a gabbronoritic mineralogy. This is consistent with latestage magma ocean assemblages predicted by petrologic models. In contrast, SPA impact melt derived from greater depths is associated with a low-Ca pyroxene-dominated assemblage. Together,
these compositional patterns are evidence for a stratified ancient upper mantle. Importantly, the incompatible-element-enriched, ilmenite-bearing ferroan gabbronoritic cumulates evidently had not participated in gravitational overturn at the time of SPA formation. Contrary to recent hypotheses invoking nearside sequestration of incompatible elements to explain hemispherical differences in crustal building and volcanic resurfacing, it follows that incompatible elements were globally distributed in the magma ocean at the time of SPA formation.
To estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults.
A Markov model was used to ...evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019.
With perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy.
Each strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.
Proton beam therapy is a commonly accepted treatment for intraocular melanomas, but the literature is lacking in descriptions of patient preferences of clinical outcomes and economic impact. In ...addition, no economic evaluations have been published regarding the incremental cost-effectiveness of proton beam therapy compared with enucleation or plaque brachytherapy, typical alternative treatments. We, therefore, conducted a cost-utility analysis of these three approaches for the treatment of intraocular melanomas.
A Markov model was constructed. Model parameters were identified from the published literature and publicly available data sources. Cost-effectiveness of each treatment was calculated in 2011 US Dollars per quality-adjusted life-year. Incremental cost-effectiveness ratios were calculated assuming enucleation as reference. One-way sensitivity analyses were conducted on all model parameters. A decision threshold of $50,000/quality-adjusted life-year was used to determine cost-effectiveness.
Enucleation had the lowest costs and quality-adjusted life-years, and plaque brachytherapy had the highest costs and quality-adjusted life-years. Compared with enucleation, the base-case incremental cost-effectiveness ratios for plaque brachytherapy and proton beam therapy were $77,500/quality-adjusted life-year and $106,100/quality-adjusted life-year, respectively. Results were highly sensitive to multiple parameters. All three treatments were considered optimal, and even dominant, depending on the values used for sensitive parameters.
Base-case analysis results suggest enucleation to be optimal. However, the optimal choice was not robust to sensitivity analyses and, depending on the assumption, both plaque brachytherapy and proton beam therapy could be considered cost-effective. Future clinical studies should focus on generating further evidence with the greatest parameter uncertainty to inform future cost-effectiveness analyses.
We present results from deep observations toward the Cygnus region using 300 hr of very high energy (VHE) γ-ray data taken with the VERITAS Cerenkov telescope array and over 7 yr of high-energy γ-ray ...data taken with the Fermi satellite at an energy above 1 GeV. As the brightest region of diffuse γ-ray emission in the northern sky, the Cygnus region provides a promising area to probe the origins of cosmic rays. We report the identification of a potential Fermi-LAT counterpart to VER J2031+415 (TeV J2032+4130) and resolve the extended VHE source VER J2019+368 into two source candidates (VER J2018+367* and VER J2020+368*) and characterize their energy spectra. The Fermi-LAT morphology of 3FGL J2021.0+4031e (the Gamma Cygni supernova remnant) was examined, and a region of enhanced emission coincident with VER J2019+407 was identified and jointly fit with the VERITAS data. By modeling 3FGL J2015.6+3709 as two sources, one located at the location of the pulsar wind nebula CTB 87 and one at the quasar QSO J2015+371, a continuous spectrum from 1 GeV to 10 TeV was extracted for VER J2016+371 (CTB 87). An additional 71 locations coincident with Fermi-LAT sources and other potential objects of interest were tested for VHE γ-ray emission, with no emission detected and upper limits on the differential flux placed at an average of 2.3% of the Crab Nebula flux. We interpret these observations in a multiwavelength context and present the most detailed γ-ray view of the region to date.
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