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To compare 2 methods of communicating polymerase chain reaction (PCR) blood-culture results: active approach utilizing on-call personnel versus passive approach utilizing notifications in the electronic health record (EHR).
Design:
Retrospective observational study.
Setting:
A tertiary-care academic medical center.
Patients:
Adult patients hospitalized with ≥1 positive blood culture containing a gram-positive organism identified by PCR between October 2014 and January 2018.
Methods:
The standard protocol for reporting PCR results at baseline included a laboratory technician calling the patient’s nurse, who would report the critical result to the medical provider. The active intervention group consisted of an on-call pager system utilizing trained pharmacy residents, whereas the passive intervention group combined standard protocol with real-time in-basket notifications to pharmacists in the EHR.
Results:
Of 209 patients, 105, 61, and 43 patients were in the control, active, and passive groups, respectively. Median time to optimal therapy was shorter in the active group compared to the passive group and control (23.4 hours vs 42.2 hours vs 45.9 hours, respectively; P = .028). De-escalation occurred 12 hours sooner in the active group. In the contaminant group, empiric antibiotics were discontinued faster in the active group (0 hours) than in the control group and the passive group (17.7 vs 7.2 hours; P = .007). Time to active therapy and days of therapy were similar.
Conclusions:
A passive, electronic method of reporting PCR results to pharmacists was not as effective in optimizing stewardship metrics as an active, real-time method utilizing pharmacy residents. Further studies are needed to determine the optimal method of communicating time-sensitive information.
Will AI-enabled capabilities increase inadvertent escalation risk? This article revisits Cold War-era thinking about inadvertent escalation to consider how Artificial Intelligence (AI) technology (especially AI augmentation of advanced conventional weapons) through various mechanisms and pathways could affect inadvertent escalation risk between nuclear-armed adversaries during a conventional crisis or conflict. How might AI be incorporated into nuclear and conventional operations in ways that affect escalation risk? It unpacks the psychological and cognitive features of escalation theorising (the security dilemma, the ‘fog of war’, and military doctrine and strategy) to examine whether and how the characteristics of AI technology, against the backdrop of a broader political-societal dynamic of the digital information ecosystem, might increase inadvertent escalation risk. Are existing notions of inadvertent escalation still relevant in the digital age? The article speaks to the broader scholarship in International Relations – notably ‘bargaining theories of war’ – that argues that the impact of technology on the cause of war occurs through its political effects, rather than tactical or operational battlefield alterations. In this way, it addresses a gap in the literature about the strategic and theoretical implications of the AI-nuclear dilemma.
Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.
Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.
In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas.
Aims
To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs.
Method
We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission.
Results
Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10–88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust)-level effects (2.0%). Risk of readmission was not associated with local availability of ADUs (adjusted odds ratio 0.96, 95% CI 0.80–1.15). Statistically significant elevated risks were identified for participants who were female, older, single, from Black or mixed ethnic groups, or from more deprived areas. Clinical predictors included shorter index admission, psychosis and being an in-patient at baseline.
Conclusions
Relapse and readmission to acute mental healthcare are common following discharge and occur early. Readmission was not influenced significantly by trust-level variables including availability of ADUs. More support for relapse prevention and symptom management may be required following discharge from acute mental healthcare.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
Methods
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
Results
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Conclusions
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
For people in mental health crisis, acute day units (ADUs) provide daily structured sessions and peer support in non-residential settings, often as an addition or alternative to crisis resolution teams (CRTs). There is little recent evidence about outcomes for those using ADUs, particularly compared with those receiving CRT care alone.
Aims
We aimed to investigate readmission rates, satisfaction and well-being outcomes for people using ADUs and CRTs.
Method
We conducted a cohort study comparing readmission to acute mental healthcare during a 6-month period for ADU and CRT participants. Secondary outcomes included satisfaction (Client Satisfaction Questionnaire), well-being (Short Warwick–Edinburgh Mental Well-being Scale) and depression (Center for Epidemiologic Studies Depression Scale).
Results
We recruited 744 participants (ADU: n = 431, 58%; CRT: n = 312, 42%) across four National Health Service trusts/health regions. There was no statistically significant overall difference in readmissions: 21% of ADU participants and 23% of CRT participants were readmitted over 6 months (adjusted hazard ratio 0.78, 95% CI 0.54–1.14). However, readmission results varied substantially by setting. At follow-up, ADU participants had significantly higher Client Satisfaction Questionnaire scores (2.5, 95% CI 1.4–3.5, P < 0.001) and well-being scores (1.3, 95% CI 0.4–2.1, P = 0.004), and lower depression scores (−1.7, 95% CI −2.7 to −0.8, P < 0.001), than CRT participants.
Conclusions
Patients who accessed ADUs demonstrated better outcomes for satisfaction, well-being and depression, and no significant differences in risk of readmission, compared with those who only used CRTs. Given the positive outcomes for patients, and the fact that ADUs are inconsistently provided in the National Health Service, their value and place in the acute care pathway needs further consideration and research.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar’s primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.
Political scientists invoke the standard rationale to justify making and using formal models. It goes like this: (1) we rely on formal models to generate predictions, (2) we treat these predictions as empirical hypotheses, and (3) we seek to test these hypotheses against evidence derived from the “real world.” I show that this interpretation of formal models as directly empirical is inadequate just insofar as it fails to capture the way we actually use them. I then offer an alternative rationale for making and using formal models. Specifically, I argue that we use models, like we use fables, for conceptual purposes.
Background: Antibiotic stewardship programs (ASPs) have traditionally focused on inpatient prescribing, but they are now mandated to involve ambulatory settings. We developed and tested an educational tool in resident physicians to empower outpatient providers to perform self-reflection stewardship (SRS) to improve their antibiotic use. Results of the first SRS workshop are reported. Methods: A 90-minute SRS workshop focusing on the evaluation and management of sinusitis in ambulatory care was developed for PGY 2-3 internal medicine residents. Participants received a 15-minute didactic on the evaluation and management of adults with sinusitis, including typical microbiology, differentiation of bacterial sinusitis, and guideline recommendations on antibiotic treatment. In a computer lab, participants were instructed how to review charts of patients they had treated with antibiotics for sinusitis during the past year using the SlicerDicer application in Epic. Over 1 hour, they worked in pairs to complete and discuss a self-reflection inventory for 5 patients from each of their respective reviews. They evaluated pertinent history, comorbidities, presenting symptoms and signs, diagnostic testing performed, and a self-assessment of the subsequent antibiotic prescribing, including appropriateness of using an antibiotic, antibiotic choice and duration. In addition, they reflected on potential patient and prescriber challenges. Residents then identified common themes and developed a personal improvement plan for antibiotic prescribing for sinusitis. The last 15 minutes were spent debriefing with ASP faculty on reasons for overprescription of antibiotics for URIs and individual improvement plans. Residents completed workshop evaluations using a Likert scale and open-ended comments. Results: In total, 26 residents participated. All (100%) agreed or strongly agreed that the SRS workshop improved their understanding of how to obtain data on their own practice habits. Moreover, 23 (88%) agreed or strongly agreed that the workshop improved their understanding of when to prescribe antibiotics and how to practice antibiotic stewardship in the outpatient setting. Also, 20 participants (77%) agreed or strongly agreed that the SRS workshop helped them gain insight into reasons why they might overprescribe antibiotics in the outpatient setting. Furthermore, 25 (96%) agreed or strongly agreed that the SRS workshop helped them identify at least 1 way they could improve their antibiotic prescribing in the outpatient setting. Conclusions: The SRS workshop was well received by residents and offers a tool to empower primary care resident physicians to access their own antibiotic prescribing data, perform a structured self-reflection, and enhance their understanding of antibiotic stewardship in the ambulatory setting. SRS is a potential tool to improve ambulatory antibiotic use.
Surgical antimicrobial prophylaxis (SAP) is commonly administered in orthopedic procedures. Research regarding SAP appropriateness for specific orthopedic procedures is limited and is required to facilitate targeted orthopedic prescriber behavior change.
Objectives:
To describe SAP prescribing and appropriateness for orthopedic procedures in Australian hospitals.
Design, setting, and participants:
Multicenter, national, quality improvement study with retrospective analysis of data collected from Australian hospitals via Surgical National Antimicrobial Prescribing Survey (Surgical NAPS) audits from January 1, 2016, to April 15, 2019, were analyzed.
Methods:
Logistic regression identified hospital, patient and surgical factors associated with appropriateness. Adjusted appropriateness was calculated from the multivariable model. Additional subanalyses were conducted on smaller subsets to calculate the adjusted appropriateness for specific orthopedic procedures.
Results:
In total, 140 facilities contributed to orthopedic audits in the Surgical NAPS, including 4,032 orthopedic surgical episodes and 6,709 prescribed doses. Overall appropriateness was low, 58.0% (n = 3,894). This differed for prescribed procedural (n = 3,978, 64.7%) and postprocedural doses (n = 2,731, 48.3%). The most common reasons for inappropriateness, when prophylaxis was required, was timing for procedural doses (50.9%) and duration for postprocedural prescriptions (49.8%). The adjusted appropriateness of each orthopedic procedure group was low for procedural SAP (knee surgery, 54.1% to total knee joint replacement, 74.1%). The adjusted appropriateness for postprocedural prescription was also low (from hand surgery, 40.7%, to closed reduction fractures, 68.7%).
Conclusions:
Orthopedic surgical specialties demonstrated differences across procedural and postprocedural appropriateness. The metric of appropriateness identifies targets for quality improvement and is meaningful for clinicians. Targeted quality improvement projects for orthopedic specialties need to be developed to support optimization of antimicrobial use.
The steep rise in the rate of psychiatric hospital detentions in England is poorly understood.
Aims
To identify explanations for the rise in detentions in England since 1983; to test their plausibility and support from evidence; to develop an explanatory model for the rise in detentions.
Method
Hypotheses to explain the rise in detentions were identified from previous literature and stakeholder consultation. We explored associations between national indicators for potential explanatory variables and detention rates in an ecological study. Relevant research was scoped and the plausibility of each hypothesis was rated. Finally, a logic model was developed to illustrate likely contributory factors and pathways to the increase in detentions.
Results
Seventeen hypotheses related to social, service, legal and data-quality factors. Hypotheses supported by available evidence were: changes in legal approaches to patients without decision-making capacity but not actively objecting to admission; demographic changes; increasing psychiatric morbidity. Reductions in the availability or quality of community mental health services and changes in police practice may have contributed to the rise in detentions. Hypothesised factors not supported by evidence were: changes in community crisis care, compulsory community treatment and prescribing practice. Evidence was ambiguous or lacking for other explanations, including the impact of austerity measures and reductions in National Health Service in-patient bed numbers.
Conclusions
Better data are needed about the characteristics and service contexts of those detained. Our logic model highlights likely contributory factors to the rise in detentions in England, priorities for future research and potential policy targets for reducing detentions.
At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
Serotonin and sympathomimetic toxicity (SST) after ingestion of amphetamine-based drugs can lead to severe morbidity and death. There have been evaluations of the safety and efficacy of on-site treatment protocols for SST at music festivals.
Problem:
The study aimed to examine the safety and efficacy of treating patients with SST on-site at a music festival using a protocol adapted from hospital-based treatment of SST.
Methods:
The study is an audit of presentations with SST over a one-year period. The primary outcome was need for ambulance transport to hospital. The threshold for safety was prospectively defined as less than 10% of patients requiring ambulance transport to hospital.
The protocol suggested patients be treated with a combination of benzodiazepines; cold intravenous (IV) fluid; specific therapies (cyproheptadine, chlorpromazine, and clonidine); rapid sequence intubation; and cooling with ice, misted water, and convection techniques.
Results:
One patient of 13 (7.7%) patients with mild or moderate SST required ambulance transport to hospital. Two of seven further patients with severe SST required transport to hospital.
Conclusions:
On-site treatment may be a safe, efficacious, and efficient alternative to urgent transport to hospital for patients with mild and moderate SST. The keys to success of the protocol tested included inclusive and clear education of staff at all levels of the organization, robust referral pathways to senior clinical staff, and the rapid delivery of therapies aimed at rapidly lowering body temperature. Further collaborative research is required to define the optimal approach to patients with SST at music festivals.
Multispectral imaging – the acquisition of spatially contiguous imaging data in a modest number (~3–16) of spectral bandpasses – has proven to be a powerful technique for augmenting panchromatic imaging observations on Mars focused on geologic and/or atmospheric context. Specifically, multispectral imaging using modern digital CCD photodetectors and narrowband filters in the 400–1100 nm wavelength region on the Mars Pathfinder, Mars Exploration Rover, Phoenix, and Mars Science Laboratory missions has provided new information on the composition and mineralogy of fine-grained regolith components (dust, soils, sand, spherules, coatings), rocky surface regions (cobbles, pebbles, boulders, outcrops, and fracture-filling veins), meteorites, and airborne dust and other aerosols. Here we review recent scientific results from Mars surface-based multispectral imaging investigations, including the ways that these observations have been used in concert with other kinds of measurements to enhance the overall scientific return from Mars surface missions.
Mexican Americans suffer from a disproportionate burden of modifiable risk factors, which may contribute to the health disparities in mild cognitive impairment (MCI) and Alzheimer’s disease (AD).
Objective:
The purpose of this study was to elucidate the impact of comorbid depression and diabetes on proteomic outcomes among community-dwelling Mexican American adults and elders.
Methods:
Data from participants enrolled in the Health and Aging Brain among Latino Elders study was utilized. Participants were 50 or older and identified as Mexican American (N = 514). Cognition was assessed via neuropsychological test battery and diagnoses of MCI and AD adjudicated by consensus review. The sample was stratified into four groups: Depression only, Neither depression nor diabetes, Diabetes only, and Comorbid depression and diabetes. Proteomic profiles were created via support vector machine analyses.
Results:
In Mexican Americans, the proteomic profile of MCI may change based upon the presence of diabetes. The profile has a strong inflammatory component and diabetes increases metabolic markers in the profile.
Conclusion:
Medical comorbidities may impact the proteomics of MCI and AD, which lend support for a precision medicine approach to treating this disease.
For patients with possible Staphylococcus aureus infection, providers must decide whether to treat empirically for methicillin-resistant S. aureus (MRSA). Nares MRSA colonization screening tests could inform decisions regarding empiric MRSA-active antibiotic use.1,2
Mercury is the only terrestrial planet other than Earth that possesses a global magnetic field, and the unique solar wind environment of the inner heliosphere has profound consequences for both the structure and dynamics of its magnetosphere. The first in situ observations of Mercury and its space environment made four decades ago by the Mariner 10 spacecraft revealed a magnetic field that is sufficiently strong to stand off the solar wind and form a magnetosphere. Many new insights into Mercury’s magnetosphere were enabled by data returned by the MESSENGER spacecraft. The extensive magnetic field and particle observations allowed detailed characterization of the magnetospheric structure and configuration. MESSENGER magnetic field observations definitively determined the orientation, moment, and location of the internal planetary magnetic dipole field. Furthermore, these observations established the configuration of the magnetopause, bow shock, and magnetospheric current systems. Plasma observations revealed the distribution and composition of plasma in the magnetosphere. We review the geometry and dominant physical processes of Mercury’s unique magnetosphere inferred from MESSENGER data, including the solar wind environment, the shape and location of magnetospheric boundaries, and the fundamental regions and configuration of the magnetosphere and transport and heating of plasma therein.
Among 469 US military veterans with an Escherichia coli clinical isolate (2012–2013), we explored healthcare and non-healthcare risk factors for having E. coli sequence type 131 and its H30 subclone (ST131-H30). Overall, 66 (14%) isolates were ST131; 51 (77%) of these were ST131-H30. After adjustment for healthcare-associated factors, ST131 remained positively associated with medical lines and nursing home residence. After adjustment for environmental factors, ST131 remained associated with wild animal contact (positive), meat consumption (negative) and pet cat exposure (negative). Thus, ST131 was associated predominantly with healthcare-associated exposures, while non-ST131 E. coli were associated with some environmental exposures.