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Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.
Laboratory-based case confirmation is an integral part of measles surveillance programmes; however, logistical constraints can delay response. Use of RDTs during initial patient contact could enhance surveillance by real-time case confirmation and accelerating public health response. Here, we evaluate performance of a novel measles IgM RDT and assess accuracy of visual interpretation using a representative collection of 125 sera from the Brazilian measles surveillance programme. RDT results were interpreted visually by a panel of six independent observers, the consensus of three observers and by relative reflectance measurements using an ESEQuant Reader. Compared to the Siemens anti-measles IgM EIA, sensitivity and specificity of the RDT were 94.9% (74/78, 87.4–98.6%) and 95.7% (45/47, 85.5-99.5%) for consensus visual results, and 93.6% (73/78, 85.7–97.9%) and 95.7% (45/47, 85.5-99.5%), for ESEQuant measurement, respectively. Observer agreement, determined by comparison between individuals and visual consensus results, and between individuals and ESEQuant measurements, achieved average kappa scores of 0.97 and 0.93 respectively. The RDT has the sensitivity and specificity required of a field-based test for measles diagnosis, and high kappa scores indicate this can be accomplished accurately by visual interpretation alone. Detailed studies are needed to establish its role within the global measles control programme.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
To assess preventability of hospital-onset bacteremia and fungemia (HOB), we developed and evaluated a structured rating guide accounting for intrinsic patient and extrinsic healthcare-related risks.
Design:
HOB preventability rating guide was compared against a reference standard expert panel.
Participants:
A 10-member panel of clinical experts was assembled as the standard of preventability assessment, and 2 physician reviewers applied the rating guide for comparison.
Methods:
The expert panel independently rated 82 hypothetical HOB scenarios using a 6-point Likert scale collapsed into 3 categories: preventable, uncertain, or not preventable. Consensus was defined as concurrence on the same category among ≥70% experts. Scenarios without consensus were deliberated and followed by a second round of rating.
Two reviewers independently applied the rating guide to adjudicate the same 82 scenarios in 2 rounds, with interim revisions. Interrater reliability was evaluated using the κ (kappa) statistic.
Results:
Expert panel consensus criteria were met for 52 scenarios (63%) after 2 rounds.
After 2 rounds, guide-based rating matched expert panel consensus in 40 of 52 (77%) and 39 of 52 (75%) cases for reviewers 1 and 2, respectively. Agreement rates between the 2 reviewers were 84% overall (κ, 0.76; 95% confidence interval [CI], 0.64–0.88]) and 87% (κ, 0.79; 95% CI, 0.65–0.94) for the 52 scenarios with expert consensus.
Conclusions:
Preventability ratings of HOB scenarios by 2 reviewers using a rating guide matched expert consensus in most cases with moderately high interreviewer reliability. Although diversity of expert opinions and uncertainty of preventability merit further exploration, this is a step toward standardized assessment of HOB preventability.
This collection of essays pays tribute to Nancy Freeman Regalado, a ground-breaking scholar in the field of medieval French literature whose research has always pushed beyond disciplinary boundaries. The articles in the volume reflect the depth and diversity of her scholarship, as well as her collaborations with literary critics, philologists, historians, art historians, musicologists, and vocalists - in France, England, and the United States. Inspired by her most recent work, these twenty-four essays are tied together by a single question, rich in ramifications: how does performance shape our understanding of medieval and pre-modern literature and culture, whether the nature of that performance is visual, linguistic, theatrical, musical, religious, didactic, socio-political, or editorial? The studies presented here invite us to look afresh at the interrelationship of audience, author, text, and artifact, to imagine new ways of conceptualizing the creation, transmission, and reception of medieval literature, music, and art.
EGLAL DOSS-QUINBY is Professor of French at Smith College; ROBERTA L. KRUEGER is Professor of French at Hamilton College; E. JANE BURNS is Professor of Women's Studies and Adjunct Professor of Comparative Literature at the University of North Carolina, Chapel Hill.
Contributors: ANNE AZÉMA, RENATE BLUMENFELD-KOSINSKI, CYNTHIA J. BROWN, ELIZABETH A. R. BROWN, MATILDA TOMARYN BRUCKNER, E. JANE BURNS, ARDIS BUTTERFIELD, KIMBERLEE CAMPBELL, ROBERT L. A. CLARK, MARK CRUSE, KATHRYN A. DUYS, ELIZABETH EMERY, SYLVIA HUOT, MARILYN LAWRENCE, KATHLEEN A. LOYSEN, LAURIE POSTLEWATE, EDWARD H. ROESNER, SAMUEL N. ROSENBERG, LUCY FREEMAN SANDLER, PAMELA SHEINGORN, HELEN SOLTERER, JANE H. M. TAYLOR, EVELYN BIRGE VITZ, LORI J. WALTERS, AND MICHEL ZINK.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Depression and anxiety in Parkinson's disease are common and frequently co-morbid, with significant impact on health outcome. Nevertheless, management is complex and often suboptimal. The existence of clinical subtypes would support stratified approaches in both research and treatment.
Method
Five hundred and thirteen patients with Parkinson's disease were assessed annually for up to 4 years. Latent transition analysis (LTA) was used to identify classes that may conform to clinically meaningful subgroups, transitions between those classes over time, and baseline clinical and demographic features that predict common trajectories.
Results
In total, 64.1% of the sample remained in the study at year 4. LTA identified four classes, a ‘Psychologically healthy’ class (approximately 50%), and three classes associated with psychological distress: one with moderate anxiety alone (approximately 20%), and two with moderate levels of depression plus moderate or severe anxiety. Class membership tended to be stable across years, with only about 15% of individuals transitioning between the healthy class and one of the distress classes. Stable distress was predicted by higher baseline depression and psychiatric history and younger age of onset of Parkinson's disease. Those with younger age of onset were also more likely to become distressed over the course of the study.
Conclusions
Psychopathology was characterized by relatively stable anxiety or anxious-depression over the 4-year period. Anxiety, with or without depression, appears to be the prominent psychopathological phenotype in Parkinson's disease suggesting a pressing need to understanding its mechanisms and improve management.
Objective: The Sequential Organ Failure Assessment (SOFA) score has been recommended for triage during a mass influx of critically ill patients, but it requires laboratory measurement of 4 parameters, which may be impractical with constrained resources. We hypothesized that a modified SOFA (MSOFA) score that requires only 1 laboratory measurement would predict patient outcome as effectively as the SOFA score.
Methods: After a retrospective derivation in a prospective observational study in a 24-bed medical, surgical, and trauma intensive care unit, we determined serial SOFA and MSOFA scores on all patients admitted during the 2008 calendar year and compared the ability to predict mortality and the need for mechanical ventilation.
Results: A total of 1770 patients (56% male patients) with a 30-day mortality of 10.5% were included in the study. Day 1 SOFA and MSOFA scores performed equally well at predicting mortality with an area under the receiver operating curve (AUC) of 0.83 (95% confidence interval 0.81-.85) and 0.84 (95% confidence interval 0.82-.85), respectively (P = .33 for comparison). Day 3 SOFA and MSOFA predicted mortality for the 828 patients remaining in the intensive care unit with an AUC of 0.78 and 0.79, respectively. Day 5 scores performed less well at predicting mortality. Day 1 SOFA and MSOFA predicted the need for mechanical ventilation on day 3, with an AUC of 0.83 and 0.82, respectively. Mortality for the highest category of SOFA and MSOFA score (>11 points) was 53% and 58%, respectively.
Conclusions: The MSOFA predicts mortality as well as the SOFA and is easier to implement in resource-constrained settings, but using either score as a triage tool would exclude many patients who would otherwise survive.
(Disaster Med Public Health Preparedness. 2010;4:277-284)
