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We surveyed physicians and patients to create a novel Desirability of outcome ranking (DOOR) for non-severe community-acquired pneumonia (CAP). Patients generally ranked uncomfortable but non-life-threatening symptoms as less desirable, while physicians focused on traditional medical outcomes. When developing DOORs, both patient and clinician perspectives should be considered.
Background: Dichotomous outcomes rarely capture the range of potential outcomes important to patients and clinicians. To address this limitation, the Desirability of Outcome Ranking (DOOR) score was created to rank potential outcomes from least to most desirable. Currently, there is no standardized method to develop a DOOR score and data are limited on whether patients and their clinicians rank outcomes similarly. We aimed: (a) to develop a novel DOOR score for adults hospitalized with community-acquired pneumonia (CAP) by surveying patients and clinicians on their preferred outcome ranking and (b) to compare their relative DOOR rankings. Methods: We created nine clinical scenarios describing the spectrum of potential outcomes of patients with CAP two weeks after initial emergency department visit. To ascertain clinician DOOR score, we used a snowball sampling method to recruit a target of 25 clinicians in specialties that regularly treat CAP. For the patient DOOR score, we recruited patients hospitalized with CAP by reviewing electronic patient lists for adults hospitalized with pneumonia. Respondents were asked to rank the 9 cases from most to least desirable in REDCap. To create the final DOOR score, we used Friedman rank sum tests to combine/collapse DOOR outcomes with scores that did not significantly differ. We used the Mann Whitney U test to compare DOOR rankings between physicians and patients. Final study results were presented to a national hospital medicine patient and family advisory committee (PFAC) for their impressions. Results: 22 patients (71% response rate) and 25 clinicians responded to our DOOR survey. Their ranked order of DOOR outcomes is shown in Table 1. Combining non-significantly different DOOR outcomes resulted in collapsing of 6 cases into 2 categories for 5 overall DOOR scores that significantly differed from each other (Table 1 for final ranking). Patients and clinicians had significantly different preferred ranking for 6 DOOR cases. Our PFAC had several hypotheses as to why rankings differed (Table 2). Conclusion: We present a novel DOOR score derived from patient and clinician reported preferences for outcomes of hospitalized adult patients with CAP. Clinicians and patients differed in their perception of certain outcomes with patients ranking symptoms that were uncomfortable but not potentially life-threatening as less desirable than physicians. Physicians tended to rank quality linked metrics such as readmission as worse than patients. When designing future trials using DOOR scores, researchers should consider including patients in DOOR score design as their perspectives may differ from clinicians.
We examine the optical counterparts of the 1 829 neutral hydrogen (H i) detections in three pilot fields in the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) using data from the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys DR10. We find that 17% (315) of the detections are optically low surface brightness galaxies (LSBGs; mean g-band surface brightness within 1 $ R_e$ of $\gt 23$ mag arcsec$^{-2}$) and 3% (55) are optically ‘dark’. We find that the gas-rich WALLABY LSBGs have low star formation efficiencies, and have stellar masses spanning five orders of magnitude, which highlights the diversity of properties across our sample. 75% of the LSBGs and all of the dark H i sources had not been catalogued prior to WALLABY. We examine the optically dark sample of the WALLABY pilot survey to verify the fidelity of the catalogue and investigate the implications for the full survey for identifying dark H i sources. We assess the H i detections without optical counterparts and identify 38 which pass further reliability tests. Of these, we find that 13 show signatures of tidal interactions. The remaining 25 detections have no obvious tidal origin, so are candidates for isolated galaxies with high H i masses, but low stellar masses and star-formation rates. Deeper H i and optical follow-up observations are required to verify the true nature of these dark sources.
To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT).
Methods:
We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact.
Results:
We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017–August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11–4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11–3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83–1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact.
Conclusions:
Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.
The mechanics underlying ice–skate friction remain uncertain despite over a century of study. In the 1930s, the theory of self-lubrication from frictional heat supplanted an earlier hypothesis that pressure melting governed skate friction. More recently, researchers have suggested that a layer of abraded wear particles or the presence of quasi-liquid molecular layers on the surface of ice could account for its slipperiness. Here, we assess the dominant hypotheses proposed to govern ice–skate friction and describe experiments conducted in an indoor skating rink aimed to provide observations to test these hypotheses. Our results indicate that the brittle failure of ice under rapid compression plays a strong role. Our observations did not confirm the presence of full-contact water films and are more consistent with the presence of lubricating ice-rich slurries at discontinuous high-pressure zones (HPZs). The presence of ice-rich slurries supporting skates through HPZs merges pressure-melting, abrasion and lubricating films as a unified hypothesis for why skates are so slippery across broad ranges of speeds, temperatures and normal loads. We suggest tribometer experiments to overcome the difficulties of investigating these processes during actual skating trials.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
Objectives:
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Methods:
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Results:
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Conclusion:
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
The First Episode Rapid Early Intervention for Eating Disorders (FREED) service model is associated with significant reductions in wait times and improved clinical outcomes for emerging adults with recent-onset eating disorders. An understanding of how FREED is implemented is a necessary precondition to enable an attribution of these findings to key components of the model, namely the wait-time targets and care package.
Aims
This study evaluated fidelity to the FREED service model during the multicentre FREED-Up study.
Method
Participants were 259 emerging adults (aged 16–25 years) with an eating disorder of <3 years duration, offered treatment through the FREED care pathway. Patient journey records documented patient care from screening to end of treatment. Adherence to wait-time targets (engagement call within 48 h, assessment within 2 weeks, treatment within 4 weeks) and care package, and differences in adherence across diagnosis and treatment group were examined.
Results
There were significant increases (16–40%) in adherence to the wait-time targets following the introduction of FREED, irrespective of diagnosis. Receiving FREED under optimal conditions also increased adherence to the targets. Care package use differed by component and diagnosis. The most used care package activities were psychoeducation and dietary change. Attention to transitions was less well used.
Conclusions
This study provides an indication of adherence levels to key components of the FREED model. These adherence rates can tentatively be considered as clinically meaningful thresholds. Results highlight aspects of the model and its implementation that warrant future examination.
OBJECTIVES/GOALS: Haptoglobin (Hp) phenotypes may affect inflammatory response after neurologic injury. We are investigating the relationship between patient Hp phenotypes and inflammatory cytokine concentrations in plasma and CSF after aneurysmal subarachnoid hemorrhage (aSAH), a severe form of hemorrhagic stroke. METHODS/STUDY POPULATION: Following IRB approval, all patients with angiographically-proven aSAH and who underwent extraventricular drain (EVD) placement were included. Patients were excluded if they were not expected to survive hospitalization or were on pre-existing anti-inflammatory agents. For all enrolled patients, plasma and CSF samples were taken on post-bleed days 3, 5, 7, and 10, processed and then frozen for later analysis. In this interim analysis, Hp phenotype was assessed through ELISA analysis of plasma samples and cytokine concentrations were determined using multiplex ELISA kits for both plasma and CSF samples. Hp phenotypes were dichotomized to either HP1 (Hp 1-1 or 1-2) or HP2 (Hp 2-2). RESULTS/ANTICIPATED RESULTS: To date, 23 aSAH patients have been enrolled in this IRB-approved study. An interim analysis of the first 13 patients has revealed eight Hp1 patients (Hp 1-1 n = 1, Hp 1-2 n = 7) and five Hp2 patients. CSF levels of IL-6 and TNF-a were greater than plasma levels in all patients at all time points. CSF levels of IL-6 appear to peak on PBD 5 (1890 ± 767 pcg/mL) and 7 (1612 ± 899 pcg/mL). The CSF IL-6 concentrations in the Hp2 group were lower (1792 ± 806 pcg/mL vs. 1952 ± 791 pcg/mL) on PBD5 but were higher (1635 ± 930 pcg/mL vs 1598 ± 943 pcg/mL) at PBD7; however, these differences did not reach statistical significance. DISCUSSION/SIGNIFICANCE OF IMPACT: This interim analysis demonstrated no statistically significant differences in plasma or CSF cytokine concentrations between patients with different Hp phenotypes. This may be due to the low number of samples or the potential confounding effect of disease-specific secondary neurological injuries.
High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
In planning interplanetary missions which involve anaerobraking manoeuvre, it is necessary to makeaccurate predictions of the aerodynamic drag actingon a vehicle during its descent. Of interest to theauthors is the Nasa initiative for exploration ofMars and its atmosphere. The Mars Pathfinder is aprobe that is expected to enter the Martianatmosphere at a relative velocity of approximately7.6 kms-1;. The forebody of this vehicleis based on a 70° blunted cone and is typical ofaerobraking designs.
In this note, a comparison is made between experimentaland numerical techniques for predicting drag inhypervelocity flow. Three different models wereexamined in this study: a 30° sharp cone; an Apolloheat shield; and a Viking heat shield. A relativelysimple analytical result for the drag on a coneprovides a convenient reference for both theexperimental and numerical results. The two heatshields are typical of those used for interplanetaryexploration, such as the Mars Pathfinder. Our aim isto give an example of how computational fluiddynamics can be used in conjunction with experimentsto obtain information about the hypervelocity flowabout re-entry vehicles.
Background: The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Methods: Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. Results: A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. Conclusion: This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.
Repeated epidemiological surveys show no decline in depression although uptake of treatments has grown. Universal depression prevention interventions are effective in schools but untested rigorously in adulthood. Selective prevention programmes have poor uptake. Universal interventions may be more acceptable during routine healthcare contacts for example antenatally. One study within routine postnatal healthcare suggested risk of postnatal depression could be reduced in non-depressed women from 11% to 8% by giving health visitors psychological intervention training. Feasibility and effectiveness in other settings, most notably antenatally, is unknown.
Method
We conducted an external pilot study using a cluster trial design consisting of recruitment and enhanced psychological training of randomly selected clusters of community midwives (CMWs), recruitment of pregnant women of all levels of risk of depression, collection of baseline and outcome data prior to childbirth, allowing time for women ‘at increased risk’ to complete CMW-provided psychological support sessions.
Results
Seventy-nine percent of eligible women approached agreed to take part. Two hundred and ninety-eight women in eight clusters participated and 186 termed ‘at low risk’ for depression, based on an Edinburgh Perinatal Depression Scale (EPDS) score of <12 at 12 weeks gestation, provided baseline and outcome data at 34 weeks gestation. All trial protocol procedures were shown to be feasible. Antenatal effect sizes in women ‘at low risk’ were similar to those previously demonstrated postnatally. Qualitative work confirmed the acceptability of the approach to CMWs and intervention group women.
Conclusion
A fully powered trial testing universal prevention of depression in pregnancy is feasible, acceptable and worth undertaking.
The mood stabilisers lithium and valproate might plausibly have differing associations with mortality because of differing effects on mental health and various physiological indicators.
Aims
To assess associations between lithium, valproate and non-suicide mortality.
Lithium was associated with significantly reduced non-suicide mortality in the intent-to-treat cohort over 0–90 days (hazard ratio (HR) = 0.67, 95% CI 0.51–0.87) but not longer. In secondary analyses, a sizeable reduction in mortality was observed during active treatment with lithium across all time periods studied (for example 365-day HR = 0.62, 95% CI 0.45–0.84), but significantly increased risks were observed among patients discontinuing lithium by 180 days (HR = 1.54, 95% CI 1.01–2.37).
Conclusions
Patients initiating lithium had lower non-suicide mortality over 0–90 days than patients initiating valproate and consistently lower non-suicide mortality among patients maintaining treatment, but elevated risk among patients discontinuing treatment by 180 days. Although residual confounding or selection effects cannot be excluded, this study suggests potential benefits to enhancing lithium treatment persistence and the monitoring of patients discontinuing lithium. There is a need for further research.
The rapid sol–gel synthesis of macroscopic quantities of nanodiamond aerogel (NDAG) is reported at standard temperature and pressure using acid-catalyzed covalent crosslinking of air-oxidized detonation nanodiamond (DND) nanocrystals. Acetonitrile acts as a polar, aprotic solvent both to form a colloidal dispersion of DND particles and to conduct acid-catalyzed polycondensation reactions between resorcinol and formaldehyde (RF) small molecule precursors. Several characterization techniques show that nanodiamond grains are connected via covalent bonding with RF molecules to form a porous, three-dimensional network. Solvent exchange into liquid carbon dioxide and subsequent supercritical drying of NDAGs are used to recover low-density (151 mg/cm3), three-dimensional monolithic aerogels that exhibit surface areas in excess of 589 m2/g. The large accessible pore volume from the rapidly synthesized, macroscopic NDAG materials suggests a range of potential applications in catalysis, sensing, energy storage, as well as inert excipients for small-molecule pharmaceuticals.
We investigated an outbreak of 396 Salmonella enterica serotype I 4,5,12:i:- infections to determine the source. After 7 weeks of extensive hypothesis-generation interviews, no refined hypothesis was formed. Nevertheless, a case-control study was initiated. Subsequently, an iterative hypothesis-generation approach used by a single interviewing team identified brand A not-ready-to-eat frozen pot pies as a likely vehicle. The case-control study, modified to assess this new hypothesis, along with product testing indicated that the turkey variety of pot pies was responsible. Review of product labels identified inconsistent language regarding preparation, and the cooking instructions included undefined microwave wattage categories. Surveys found that most patients did not follow the product's cooking instructions and did not know their oven's wattage. The manufacturer voluntarily recalled pot pies and improved the product's cooking instructions. This investigation highlights the value of careful hypothesis-generation and the risks posed by frozen not-ready-to-eat microwavable foods.