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Background: In an effort to reduce inappropriate testing of hospital-onset Clostridioides difficile infection (HO-CDI), we sequentially implemented 2 strategies: an electronic health record-based clinical decision support tool that alerted ordering physicians about potentially inappropriate testing without a hard stop (intervention period 1), replaced by mandatory infectious diseases attending physician approval for any HO-CDI test order (intervention period 2). We analyzed appropriate HO-CDI testing rates of both intervention periods. Methods: We performed a retrospective study of patients 18 years or older who had an HO-CDI test (performed after hospital day 3) during 3 different periods: baseline (no intervention, September 2014–February 2015), intervention 1 (clinical decision support tool only, April 2015–September 2015), and intervention 2 (ID approval only, December 2017–September 2018). From each of the 3 periods, we randomly selected 150 patients who received HO-CDI testing (450 patients total). We restricted the study to the general medicine, bone marrow transplant, medical intensive care, and neurosurgical intensive care units. We assessed each HO-CDI test for appropriateness (see Table 1 for criteria), and we compared rates of appropriateness using the χ2 test or Kruskall-Wallis test, where appropriate. Results: In our cohort of 450 patients, the median age was 61 years, and the median hospital length of stay was 20 days. The median hospital day that HO-CDI testing was performed differed among the 3 groups: 12 days at baseline, 10 days during intervention 1, and 8.5 days during intervention 2 (P < .001). Appropriateness of HO-CDI testing increased from the baseline with both interventions, but mandatory ID approval was associated with the highest rate of testing appropriateness (Fig. 1). Reasons for inappropriate ordering did not differ among the periods, with <3 documented stools being the most common criterion for inappropriateness. During intervention 2, among the 33 inappropriate tests, 8 (24%) occurred where no approval from an ID attending was recorded. HO-CDI test positivity rates during the 3 time periods were 12%, 11%, and 21%, respectively (P = .03). Conclusions: We found that both the clinical decision support tool and mandatory ID attending physician approval interventions improved appropriateness of HO-CDI testing. Mandatory ID attending physician approval leading to the highest appropriateness rate. Even with mandatory ID attending physician approval, some tests continued to be ordered inappropriately per retrospective chart review; we suspect that this is partly explained by underdocumentation of criteria such as stool frequency. In healthcare settings where appropriateness of HO-CDI testing is not optimal, mandatory ID attending physician approval may provide an option beyond clinical decision-support tools.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
OBJECTIVES/SPECIFIC AIMS: (1) Assess if the total duration of EEG suppression during a protocolized exposure to general anesthesia predicts cognitive performance in multiple cognitive domains immediately following emergence from anesthesia. (2) Assess if the total duration of EEG suppression in the same individuals predicts the rate of cognitive recovery in a three-hour period following emergence from anesthesia. METHODS/STUDY POPULATION: This was a non-specified substudy of NCT01911195, a multicenter investigation taking place at the University of Michigan, University of Pennsylvania, and Washington University in St. Louis. 30 healthy volunteers aged 20-40 years were recruited to receive general anesthesia. Participants in the anesthesia arm were anesthetized for three hours at isoflurane levels compatible with surgery (1.3 MAC). Multichannel sensor nets were used for EEG acquisition during the anesthetic exposure. EEG suppression was detected through automated voltage-thresholded classification of 2-second signal epochs, with concordance assessed across sensors. Following return of responsiveness to verbal commands, participants completed up to three hours of serial cognitive tests assessing executive function, reaction time, cognitive throughput, and working memory. Non-linear mixed effects models will be used to estimate the initial cognitive deficit and the rate of cognitive recovery following anesthetic exposure; these measures of cognitive function will be assessed in relation to total duration of suppression during anesthesia. RESULTS/ANTICIPATED RESULTS: Participants displayed wide variability in the total amount of suppression during anesthesia, with a median of 31.2 minutes and range from 0 minutes to 115.2 minutes. Initial analyses suggest that greater duration of burst suppression had a weak relationship with participants’ initial cognitive deficits upon return of responsiveness from anesthesia. Model generation of rate of recovery following anesthetic exposure is pending, but we anticipate this will also have a weak relationship with burst suppression. DISCUSSION/SIGNIFICANCE OF IMPACT: In healthy adults receiving a standardized exposure to anesthesia without surgery, burst suppression appears to be a poor predictor of post-anesthesia cognitive task performance. This suggests that burst suppression may have limited utility as a predictive marker of post-operative cognitive functioning, particularly in young adults without significant illness.
The aim of the present study was to evaluate the association between depression and SSRI monotherapy and frailty both baseline and prospectively in older adults.
Prospective cohort study, 12-month follow-up.
Geriatric outpatient clinic in São Paulo, Brazil.
A total of 811 elderly adults aged 60 or older.
Depression was diagnosed as follows: (1) a diagnosis of major depression disorder (MDD) according to DSM-5; or (2) an incomplete diagnosis of MDD, referred to as minor or subsyndromic depression, plus Geriatric Depression Scale 15-itens ≥ 6 points, and social or functional impairment secondary to depressive symptoms and observed by relatives. Frailty evaluation was performed through the FRAIL questionnaire, which is a self-rated scale. Trained investigators blinded to the baseline assessment conducted telephone calls to evaluate frailty after 12-month follow-up. The association between depression and the use of SSRI with frailty was estimated through a generalized estimating equation adjusted for age, gender, total drugs, and number of comorbidities.
Depression with SSRI use was associated with frailty at baseline (OR 2.82, 95% CI = 1.69–4.69) and after 12 months (OR 2.75, 95% CI = 1.84–4.11). Additionally, depression with SSRI monotherapy was also associated with FRAIL subdomains Physical Performance (OR 1.99, 95% CI = 1.29–3.07) and Health Status (OR 4.64, 95% CI = 2.11–10.21). SSRI use, without significant depressive symptoms, was associated with subdomain Health Status (OR 1.52, 95% CI = 1.04–2.23).
It appears that depression with SSRI is associated to frailty, and this association cannot be explained only by antidepressant use.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days–12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30–132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15–100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.
Kinetic modeling of laser-ion beam generation from the “break-out afterburner” (BOA) has been modeled for several deuteron-rich solid-density target foils. Modeling the transport of these beams in a beryllium converter shows as much as a fourfold increase in neutron yield over the present state of the art through the use of alternative target materials. Additionally, species-separation dynamics during the BOA can be exploited to control the hardness of the neutron spectra, of interest for, for example, enhancing penetrability in shielded material in active neutron interrogation settings.
Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster.
We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties.
The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature.
The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127–137)
Alnico alloys have long been used as strong permanent magnets because of their ferromagnetism and high coercivity. Understanding their structural details allows for better prediction of the resulting magnetic properties. However, quantitative three-dimensional characterization of the phase separation in these alloys is still challenged by the spatial quantification of nanoscale phases. Herein, we apply a dual tomography approach, where correlative scanning transmission electron microscopy (STEM) energy-dispersive X-ray spectroscopic (EDS) tomography and atom probe tomography (APT) are used to investigate the initial phase separation process of an alnico 8 alloy upon non-magnetic annealing. STEM-EDS tomography provides information on the morphology and volume fractions of Fe–Co-rich and Νi–Al-rich phases after spinodal decomposition in addition to quantitative information of the composition of a nanoscale volume. Subsequent analysis of a portion of the same specimen by APT offers quantitative chemical information of each phase at the sub-nanometer scale. Furthermore, APT reveals small, 2–4 nm Fe-rich α1 phases that are nucleated in the Ni-rich α2 matrix. From this information, we show that phase separation of the alnico 8 alloy consists of both spinodal decomposition and nucleation and growth processes. The complementary benefits and challenges associated with correlative STEM-EDS and APT are discussed.
Objectives: Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects. Methods: Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto-parietal networks were also investigated. Results: In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist – Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA. Conclusions: FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631–642)
We present the results of two 2.3 μm near-infrared (NIR) radial velocity (RV) surveys to detect exoplanets around 36 nearby and young M dwarfs. We use the CSHELL spectrograph (R ~ 46,000) at the NASA InfraRed Telescope Facility (IRTF), combined with an isotopic methane absorption gas cell for common optical path relative wavelength calibration. We have developed a sophisticated RV forward modeling code that accounts for fringing and other instrumental artifacts present in the spectra. With a spectral grasp of only 5 nm, we are able to reach long-term radial velocity dispersions of ~20–30 m s−1 on our survey targets.
Studies have shown the clock-drawing test (CDT) to be a useful screening test that differentiates between normal, elderly populations, and those diagnosed with dementia. However, the results of studies which have looked at the utility of the CDT to help differentiate Alzheimer's disease (AD) from other dementias have been conflicting. The purpose of this study was to explore the utility of the CDT in discriminating between patients with AD and other types of dementia.
A review was conducted using MEDLINE, PsycINFO, and Embase. Search terms included clock drawing or CLOX and dementia or Parkinson's Disease or AD or dementia with Lewy bodies (DLB) or vascular dementia (VaD).
Twenty studies were included. In most of the studies, no significant differences were found in quantitative CDT scores between AD and VaD, DLB, and Parkinson's disease dementia (PDD) patients. However, frontotemporal dementia (FTD) patients consistently scored higher on the CDT than AD patients. Qualitative analyses of errors differentiated AD from other types of dementia.
Overall, the CDT score may be useful in distinguishing between AD and FTD patients, but shows limited value in differentiating between AD and VaD, DLB, and PDD. Qualitative analysis of the type of CDT errors may be a useful adjunct in the differential diagnosis of the types of dementias.
To assess the relative validity and reproducibility of the quantitative FFQ used in the Tzu Chi Health Study (TCHS).
The reproducibility was evaluated by comparing the baseline FFQ with the 2-year follow-up FFQ. The validity was evaluated by comparing the baseline FFQ with 3 d dietary records and biomarkers (serum folate and vitamin B12). Median comparison, cross-classification and Spearman correlation with and without energy adjustment and deattenuation for day-to-day variation were assessed.
TCHS is a prospective cohort containing a high proportion of true vegetarians and part-time vegetarians (regularly consuming a vegetarian diet without completely avoiding meat).
Subsets of 103, seventy-eight and 1528 TCHS participants were included in the reproducibility, dietary record-validity and biomarker-validity studies, respectively.
Correlations assessing the reproducibility for repeat administrations of the FFQ were in the range of 0·46–0·65 for macronutrients and 0·35–0·67 for micronutrients; the average same quartile agreement was 40%. The correlation between FFQ and biomarkers was 0·41 for both vitamin B12 and folate. Moderate to good correlations between the baseline FFQ and dietary records were found for energy, protein, carbohydrate, saturated and monounsaturated fat, fibre, vitamin C, vitamin A, K, Ca, Mg, P, Fe and Zn (average crude correlation: 0·47 (range: 0·37–0·66); average energy-adjusted correlation: 0·43 (range: 0·38–0·55); average energy-adjusted deattenuated correlation: 0·50 (range: 0·44–0·66)) with same quartile agreement rate of 39% (range: 35–45%), while misclassification to the extreme quartile was rare (average: 4% (range: 0–6%)).
The FFQ is a reliable and valid tool to rank relative intake of major nutrients for TCHS participants.