Abstract Introduction Delays in adequate antimicrobial treatment contribute to high cost and mortality in sepsis. Polymerase chain reaction (PCR) assays are used alongside conventional cultures to accelerate the identification of microorganisms. We analyze the impact on medical outcomes and healthcare costs if improved adequacy of antimicrobial therapy is achieved by providing immediate coverage after positive PCR reports. Methods A mathematical prediction model describes the impact of PCR-based rapid adjustment of antimicrobial treatment. The model is applied to predict cost and medical outcomes for 221 sepsis episodes of 189 post-surgical and intensive care unit (ICU) sepsis patients with available PCR data from a prospective, observational trial of a multiplex PCR assay in five hospitals. While this trial demonstrated reduction of inadequate treatment days, data on outcomes associated with reduced inadequate initial antimicrobial treatment had to be obtained from two other, bigger, studies which involved 1,147 (thereof 316 inadequately treated) medical or surgical ICU patients. Our results are reported with the (5% to 95%) percentile ranges from Monte Carlo simulation in which the input parameters were randomly and independently varied according to their statistical characterization in the three underlying studies. The model allows predictions also for different patient groups or PCR assays. Results A total of 13.1% of PCR tests enabled earlier adequate treatment. We predict that cost for PCR testing (300 €/test) can be fully recovered for patients above 717 € (605 € to 1,710 €) daily treatment cost. A 2.6% (2.0 to 3.2%) absolute reduction of mortality is expected. Cost per incremental survivor calculates to 11,477 € (9,321 € to 14,977 €) and incremental cost-effectiveness ratio to 3,107 € (2,523 € to 4,055 €) per quality-adjusted life-year. Generally, for ICU patients with >25% incidence of inadequate empiric antimicrobial treatment, and at least 15% with a positive blood culture, PCR represents a cost-neutral adjunct method. Conclusions Rapid PCR identification of microorganisms has the potential to become a cost-effective component for managing sepsis. The prediction model tested with data from three observational trials should be utilized as a framework to deepen insights when integrating more complementary data associated with utilization of molecular assays in the management of sepsis.

Purpose

Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content.

Methods

New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD.

Results

Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose.

Conclusions

HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.

The Dark Energy Spectroscopic Instrument (DESI) was designed to conduct a survey covering 14,000 deg2 over 5 yr to constrain the cosmic expansion history through precise measurements of baryon acoustic oscillations (BAO). The scientific program for DESI was evaluated during a 5 month survey validation (SV) campaign before beginning full operations. This program produced deep spectra of tens of thousands of objects from each of the stellar Milky Way Survey (MWS), Bright Galaxy Survey (BGS), luminous red galaxy (LRG), emission line galaxy (ELG), and quasar target classes. These SV spectra were used to optimize redshift distributions, characterize exposure times, determine calibration procedures, and assess observational overheads for the 5 yr program. In this paper, we present the final target selection algorithms, redshift distributions, and projected cosmology constraints resulting from those studies. We also present a One-Percent Survey conducted at the conclusion of SV covering 140 deg2 using the final target selection algorithms with exposures of a depth typical of the main survey. The SV indicates that DESI will be able to complete the full 14,000 deg2 program with spectroscopically confirmed targets from the MWS, BGS, LRG, ELG, and quasar programs with total sample sizes of 7.2, 13.8, 7.46, 15.7, and 2.87 million, respectively. These samples will allow exploration of the Milky Way halo, clustering on all scales, and BAO measurements with a statistical precision of 0.28% over the redshift interval z < 1.1, 0.39% over the redshift interval 1.1 < z < 1.9, and 0.46% over the redshift interval 1.9 < z < 3.5.

The Dark Energy Spectroscopic Instrument (DESI) has embarked on an ambitious five-year survey to explore the nature of dark energy with spectroscopy of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the Baryon Acoustic Oscillation method to measure distances from the nearby universe to z > 3.5, as well as measure the growth of structure and probe potential modifications to general relativity. In this paper we describe the significant instrumentation we developed for the DESI survey. The new instrumentation includes a wide-field, 3.2-deg diameter prime-focus corrector that focuses the light onto 5020 robotic fiber positioners on the 0.812 m diameter, aspheric focal surface. The positioners and their fibers are divided among ten wedge-shaped petals. Each petal is connected to one of ten spectrographs via a contiguous, high-efficiency, nearly 50 m fiber cable bundle. The ten spectrographs each use a pair of dichroics to split the light into three channels that together record the light from 360 - 980 nm with a resolution of 2000 to 5000. We describe the science requirements, technical requirements on the instrumentation, and management of the project. DESI was installed at the 4-m Mayall telescope at Kitt Peak, and we also describe the facility upgrades to prepare for DESI and the installation and functional verification process. DESI has achieved all of its performance goals, and the DESI survey began in May 2021. Some performance highlights include RMS positioner accuracy better than 0.1", SNR per \sqrt{\AA} > 0.5 for a z > 2 quasar with flux 0.28e-17 erg/s/cm^2/A at 380 nm in 4000s, and median SNR = 7 of the [OII] doublet at 8e-17 erg/s/cm^2 in a 1000s exposure for emission line galaxies at z = 1.4 - 1.6. We conclude with highlights from the on-sky validation and commissioning of the instrument, key successes, and lessons learned. (abridged)

The Dark Energy Spectroscopic Instrument (DESI) embarked on an ambitious 5 yr survey in 2021 May to explore the nature of dark energy with spectroscopic measurements of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the baryon acoustic oscillation method to measure distances from the nearby universe to beyond redshift z > 3.5, and employ redshift space distortions to measure the growth of structure and probe potential modifications to general relativity. We describe the significant instrumentation we developed to conduct the DESI survey. This includes: a wide-field, 3.°2 diameter prime-focus corrector; a focal plane system with 5020 fiber positioners on the 0.812 m diameter, aspheric focal surface; 10 continuous, high-efficiency fiber cable bundles that connect the focal plane to the spectrographs; and 10 identical spectrographs. Each spectrograph employs a pair of dichroics to split the light into three channels that together record the light from 360-980 nm with a spectral resolution that ranges from 2000-5000. We describe the science requirements, their connection to the technical requirements, the management of the project, and interfaces between subsystems. DESI was installed at the 4 m Mayall Telescope at Kitt Peak National Observatory and has achieved all of its performance goals. Some performance highlights include an rms positioner accuracy of better than 0.″1 and a median signal-to-noise ratio of 7 of the [O ii] doublet at 8 × 10-17 erg s-1 cm-2 in 1000 s for galaxies at z = 1.4-1.6. We conclude with additional highlights from the on-sky validation and commissioning, key successes, and lessons learned.

The Dark Energy Spectroscopic Instrument (DESI) completed its 5 month Survey Validation in 2021 May. Spectra of stellar and extragalactic targets from Survey Validation constitute the first major data sample from the DESI survey. This paper describes the public release of those spectra, the catalogs of derived properties, and the intermediate data products. In total, the public release includes good-quality spectral information from 466,447 objects targeted as part of the Milky Way Survey, 428,758 as part of the Bright Galaxy Survey, 227,318 as part of the Luminous Red Galaxy sample, 437,664 as part of the Emission Line Galaxy sample, and 76,079 as part of the Quasar sample. In addition, the release includes spectral information from 137,148 objects that expand the scope beyond the primary samples as part of a series of secondary programs. Here, we describe the spectral data, data quality, data products, Large-Scale Structure science catalogs, access to the data, and references that provide relevant background to using these spectra.