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Validate a public health model identifying patients at high risk for carbapenem-resistant Enterobacterales (CRE) on admission and evaluate performance across a healthcare network.
Design:
Retrospective case-control studies
Participants:
Adults hospitalized with a clinical CRE culture within 3 days of admission (cases) and those hospitalized without a CRE culture (controls).
Methods:
Using public health data from Atlanta, GA (1/1/2016–9/1/2019), we validated a CRE prediction model created in Chicago. We then closely replicated this model using clinical data from a healthcare network in Atlanta (1/1/2015–12/31/2021) (“Public Health Model”) and optimized performance by adding variables from the healthcare system (“Healthcare System Model”). We frequency-matched cases and controls based on year and facility. We evaluated model performance in validation datasets using area under the curve (AUC).
Results:
Using public health data, we matched 181 cases to 764,408 controls, and the Chicago model performed well (AUC 0.85). Using clinical data, we matched 91 cases to 384,013 controls. The Public Health Model included age, prior infection diagnosis, number of and mean length of stays in acute care hospitalizations (ACH) in the prior year. The final Healthcare System Model added Elixhauser score, antibiotic days of therapy in prior year, diabetes, admission to the intensive care unit in prior year and removed prior number of ACH. The AUC increased from 0.68 to 0.73.
Conclusions:
A CRE risk prediction model using prior healthcare exposures performed well in a geographically distinct area and in an academic healthcare network. Adding variables from healthcare networks improved model performance.
Contact tracing for COVID-19 in England operated from May 2020 to February 2022. The clinical, demographic and exposure information collected on cases and their contacts offered a unique opportunity to study secondary transmission. We aimed to quantify the relative impact of host factors and exposure settings on secondary COVID-19 transmission risk using 550,000 sampled transmission links between cases and their contacts. Links, or ‘contact episodes’, were established where a contact subsequently became a case, using an algorithm accounting for incubation period, setting, and contact date. A mixed-effects logistic regression model was used to estimate adjusted odds of transmission. Of sampled episodes, 8.7% resulted in secondary cases. Living with a case (71% episodes) was the most significant risk factor (aOR = 2.6, CI = 1.9–3.6). Other risk factors included unvaccinated status (aOR = 1.2, CI = 1.2–1.3), symptoms, and older age (66–79 years; aOR = 1.4, CI = 1.4–1.5). Whilst global COVID-19 strategies emphasized protection outside the home, including education, travel, and gathering restrictions, this study evidences the relative importance of household transmission. There is a need to reconsider the contribution of household transmission to future control strategies and the requirement for effective infection control within households.
Background: Prompt identification of patients colonized or infected with carbapenem-resistant Enterobacterales (CRE) upon admission can help ensure rapid initiation of infection prevention measures and may reduce intrafacility transmission of CRE. The Chicago CDC Prevention Epicenters Program previously created a CRE prediction model using state-wide public health data (doi: 10.1093/ofid/ofz483). We evaluated how well a similar model performed using data from a single academic healthcare system in Atlanta, Georgia, and we sought to determine whether including additional variables improved performance. Methods: We performed a case–control study using electronic medical record data. We defined cases as adult encounters to acute-care hospitals in a 4-hospital academic healthcare system from January 1, 2014, to December 31, 2021, with CRE identified from a clinical culture within the first 3 hospital days. Only the first qualifying encounter per patient was included. We frequency matched cases to control admissions (no CRE identified) from the same hospital and year. Using multivariable logistic regression, we compared 2 models. The “public health model” included 4 variables from the Chicago Epicenters model (age, number of hospitalizations in the prior 365 days, mean length of stay in hospitalizations in the prior 365 days, and hospital admission with an infection diagnosis in the prior 365 days). The “healthcare system model” added 4 additional variables (admission to the ICU in the prior 365 days, malignancy diagnosis, Elixhauser score and inpatient antibiotic days of therapy in the prior 365 days) to the public health model. We used billing codes to determine Elixhauser score, malignancy status, and recent infection diagnoses. We compared model performance using the area under the receiver operating curve (AUC). Results: We identified 105 cases and 441,460 controls (Table 1). CRE was most frequently identified in urine cultures (46%). All 4 variables included in the public health model and the 4 additional variables in the healthcare system model were all significantly associated with being a case in unadjusted analyses (Table 1). The AUC for the public health model was 0.76, and the AUC for the healthcare system model was 0.79 (Table 2; Fig. 1). In both models, a prior admission with an infection diagnosis was the most significant risk factor. Conclusions: A modified CRE prediction model developed using public health data and focused on prior healthcare exposures performed reasonably well when applied to a different academic healthcare system. The addition of variables accessible in large healthcare networks did not meaningfully improve model discrimination.
Edited by
David Lynch, Federal Reserve Board of Governors,Iftekhar Hasan, Fordham University Graduate Schools of Business,Akhtar Siddique, Office of the Comptroller of the Currency
This chapter examines how banks’ Value-at-Risk (VaR) models performed during the COVID-19 crisis using regulatory trading desk-level data. It first evaluates whether banks’ VaR models were incomplete by checking whether various factors predict backtesting exceptions. Backtesting exceptions from the past ten business days and the level of the VIX forecast future exceptions. Predictability from past backtesting exceptions rises during the COVID-19 crisis relative to 2019. The results do not find any single market factor that related to contemporaneous backtesting exceptions. These results hold both in the aggregate and across asset classes.
We outline the potential for integrating economic and evolutionary approaches to marriage and the family. Our broad argument is that the approaches share a concern for competition. Evolutionary scholars are concerned with the fitness consequences of competition and economists are centrally concerned with the nature of competition: how the allocation of scarce resources is mediated by potentially complex forms of social interaction and conflicts of interest. We illustrate our argument by focusing on conceptual and empirical approaches to a topic of interest to economists and evolutionary scholars: polygynous marriage. In comparing conceptual approaches, we distinguish between those that emphasise the physical environment and those that emphasise the social environment. We discuss some advantages of analysing marriage through the lens of competitive markets, and outline some of the ways that economists analyse the emergence of rules governing the family. In discussing empirical approaches to polygynous marriage, we describe how a concern for informing contemporary policy leads economists to focus on the consequences of polygyny, and in particular we describe some of the ways in which economists attempt to distinguish causal effects from selection effects.
Electroanatomic mapping systems are increasingly used during ablations to decrease the need for fluoroscopy and therefore radiation exposure. For left-sided arrhythmias, transseptal puncture is a common procedure performed to gain access to the left side of the heart. We aimed to demonstrate the radiation exposure associated with transseptal puncture.
Methods:
Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry. Patients with left-sided accessory pathway-mediated tachycardia, with a structurally normal heart, who had a transseptal puncture, and were under 22 years of age were included. Those with previous ablations, concurrent diagnostic or interventional catheterisation, and missing data for fluoroscopy use or procedural outcomes were excluded. Patients with a patent foramen ovale who did not have a transseptal puncture were selected as the control group using the same criteria. Procedural outcomes were compared between the two groups.
Results:
There were 284 patients in the transseptal puncture group and 70 in the patent foramen ovale group. The transseptal puncture group had a significantly higher mean procedure time (158.8 versus 131.4 minutes, p = 0.002), rate of fluoroscopy use (38% versus 7%, p < 0.001), and mean fluoroscopy time (2.4 versus 0.6 minutes, p < 0.001). The acute success and complication rates were similar.
Conclusions:
Performing transseptal puncture remains a common reason to utilise fluoroscopy in the era of non-fluoroscopic ablation. Better tools are needed to make non-fluoroscopic transseptal puncture more feasible.
Patients with CHD can be exposed to high levels of cumulative ionising radiation. Utilisation of electroanatomic mapping during catheter ablation leads to reduced radiation exposure in the general population but has not been well studied in patients with CHD. This study evaluated the radiation sparing benefit of using three-dimensional mapping in patients with CHD.
Methods:
Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy multi-institutional registry. Patients with CHD were selected. Those with previous ablations, concurrent diagnostic or interventional catheterisation and unknown arrhythmogenic foci were excluded. The control cohort was matched for operating physician, arrhythmia mechanism, arrhythmia location, weight and age. The procedure time, rate of fluoroscopy use, fluoroscopy time, procedural success, complications, and distribution of procedures per year were compared between the two groups.
Results:
Fifty-six patients with congenital heart disease and 56 matched patients without CHD were included. The mean total procedure time was significantly higher in patients with CHD (212.6 versus 169.5 minutes, p = 0.003). Their median total fluoroscopy time was 4.4 minutes (compared to 1.8 minutes), and their rate of fluoroscopy use was 23% (compared to 13%). The acute success and minor complication rates were similar and no major complications occurred.
Conclusions:
With the use of electroanatomic mapping during catheter ablation, fluoroscopy use can be reduced in patients with CHD. The majority of patients with CHD received zero fluoroscopy.
Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.
Methods
MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.
Results
VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.
Conclusions
Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.
Catheter ablation is a safe and effective therapy for the treatment of supraventricular tachycardia in children. Current improvements in technology have allowed progressive reduction in radiation exposure associated with the procedure. To assess the impact of three-dimensional mapping, we compared acute procedural results collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to published results from the Prospective Assessment after Pediatric Cardiac Ablation study.
Methods:
Inclusion and exclusion criteria from the Prospective Assessment after Pediatric Cardiac Ablation study were used as guidelines to select patient data from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to compare acute procedural outcomes between cohorts. Outcomes assessed include procedural and fluoroscopy exposure times, success rates of procedure, and complications.
Results:
In 786 ablation procedures, targeting 498 accessory pathways and 288 atrioventricular nodal reentrant tachycardia substrates, average procedural time (156.5 versus 206.7 minutes, p < 0.01), and fluoroscopy time (1.2 versus 38.3 minutes, p < 0.01) were significantly shorter in the study group. Success rates for the various substrates were similar except for manifest accessory pathways which had a significantly higher success rate in the study group (96.4% versus 93.0%, p < 0.01). Major complication rates were significantly lower in the study group (0.3% versus 1.6%, p < 0.01).
Conclusions:
In a large, multicentre study, three-dimensional systems show favourable improvements in clinical outcomes in children undergoing catheter ablation of supraventricular tachycardia compared to the traditional fluoroscopic approach. Further improvements are anticipated as technology advances.
To describe the epidemiology of carbapenem-resistant Enterobacterales (CRE) bacteriuria and to determine whether urinary catheters increase the risk of subsequent CRE bacteremia.
Design:
Using active population- and laboratory-based surveillance we described a cohort of patients with incident CRE bacteriuria and identified risk factors for developing CRE bacteremia within 1 year.
Setting:
The study was conducted among the 8 counties of Georgia Health District 3 (HD3) in Atlanta, Georgia.
Patients:
Residents of HD3 with CRE first identified in urine between 2012 and 2017.
Results:
We identified 464 patients with CRE bacteriuria (mean yearly incidence, 1.96 cases per 100,000 population). Of 425 with chart review, most had a urinary catheter (56%), and many resided in long-term care facilities (48%), had a Charlson comorbidity index >3 (38%) or a decubitus ulcer (37%). 21 patients (5%) developed CRE bacteremia with the same organism within 1 year. Risk factors for subsequent bacteremia included presence of a urinary catheter (odds ratio [OR], 8.0; 95% confidence interval [CI], 1.8–34.9), central venous catheter (OR, 4.3; 95% CI, 1.7–10.6) or another indwelling device (OR, 4.3; 95% CI, 1.6–11.4), urine culture obtained as an inpatient (OR, 5.7; 95% CI, 1.3–25.9), and being in the ICU in the week prior to urine culture (OR, 2.9; 95% CI, 1.1–7.8). In a multivariable analysis, urinary catheter increased the risk of CRE bacteremia (OR, 5.3; 95% CI, 1.2–23.6).
Conclusions:
In patients with CRE bacteriuria, urinary catheters increase the risk of CRE bacteremia. Future interventions should aim to reduce inappropriate insertion and early removal of urinary catheters.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
$\sim$
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
$+41^\circ$
made over a 288-MHz band centred at 887.5 MHz.
Background: Carbapenem-resistant Enterobacteriaceae (CRE), particularly carbapenemase-producing (CP) CRE, pose a major public health threat. In 2016, the phenotypic definition of CRE expanded to include ertapenem resistance to improve sensitivity for detecting CP-CRE. We compared characteristics of CRE resistant to ertapenem only (CRE-EO) to CRE resistant to ≥1 other carbapenem (CRE-O). Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in metropolitan Atlanta. CRE cases were defined as any Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, Enterobacter cloacae complex, or Enterobacter aerogenes resistant to ≥1 carbapenem by the clinical laboratory and isolated from urine or a sterile site between 2016 and 2018. Data were extracted from retrospective chart review and 90-day mortality from Georgia vital statistics for 2016–2017. Polymerase chain reaction (PCR) for carbapenemase genes was performed on a convenience sample of isolates by the CDC or Georgia Public Health Laboratory. We compared characteristics of CRE-EO cases to CRE-O cases using χ2 tests or t tests. Results: Among 927 CRE isolates, 553 (60%) were CRE-EO. CRE-EO were less frequently isolated from blood (5% vs 12%; P < .01) and less commonly K. pneumoniae (21% vs 58%; P < .01) than CRE-O. CRE-EO cases were more often women (65% vs 50%; P < .01), had a lower Charlson comorbidity index (mean ± SD, 2.4±2.3 vs 3.0±2.6; P < .01), and were less commonly at a long-term care facility (24% vs 31%) or hospital (15% vs 21%; P < .01) in the 4 days prior to the CRE culture. CRE-EO were more susceptible to all antibiotics tested at the clinical laboratory (P < .01) except for tigecycline (P = 1.0) (Table 1). Of the 300 (32%) isolates tested for carbapenemase genes, 98 (33%) were positive (7% CRE-EO vs 62% CRE-O; P < .01). Of the CP isolates, we identified blaKPC in 93 cases (95%), blaNDM in 3 cases (3%), blaOXA-48-like in 2 cases (2%). CRE-EO cases had lower 90-day mortality (13% vs 21%; P < .01). Conclusions: CRE-EO are epidemiologically distinct from CRE-O and are less likely to harbor carbapenemase genes. CRE-EO may require less intensive infection prevention interventions and have more therapeutic options.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent a significant antibiotic resistance threat, in part because carbapenemase genes can spread on mobile genetic elements. Here, we describe the molecular epidemiology and outcomes of patients with CRE bacteriuria from the same city in a nonoutbreak setting. Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in Atlanta. We studied a cohort of patients with CRE (resistant to all tested third-generation cephalosporins and ≥1 carbapenem, excluding ertapenem) first identified in urine, and not in a prior or simultaneous sterile site, between 2012 and 2015. Whole-genome sequencing (WGS) was performed on a convenience sample. We obtained epidemiologic and outcome data through chart review and Georgia Vital Statistics records (90-day mortality). Using WGS, we created a core-genome alignment-based phylogenetic tree of the Klebsiella pneumoniae isolates and calculated the SNP difference between each sample. Using SAS version 9.4 software, we performed the Fisher exact test and univariable odds ratios (OR) with 95% CI to compare patient isolates with and without a carbapenemase gene. Results: Among 81 patients included, the median age was 68 (IQR, 57–74) years, and most were female (58%), black (60%), and resided in a long-term care facility 4 days prior to culture isolation (53%). Organisms isolated were K. pneumoniae (84%), Escherichia coli (7%), Enterobacter cloacae (7%), and Klebsiella oxytoca (1%). WGS identified at least 1 β-lactamase gene in 91% of the isolates; 85% contained a carbapenemase gene, the most frequent of which was blaKPC-3 (94%). Patients with CRE containing a carbapenemase gene were more likely to be black (OR, 3.7; 95% CI, 1.0–13.8) and to have K. pneumoniae (OR, 8.9; 95% CI, 2.2–35.0). Using a core-genome alignment of 3,708 genes (~63% of the complete genome), we identified a median of 67 (IQR, 23–3,881) SNP differences between each K. pneumoniae isolate. A phylogenetic tree identified clustering around carbapenemase gene and multilocus sequence type (84% were ST 258) but not based on referring laboratory or county of residence (Fig. 1). Although 7% of patients developed an invasive CRE infection within 1 year and 21% died within 90 days, having a carbapenemase gene was not associated with these outcomes. Conclusions: Molecular sequencing of a convenience sample of CRE bacteriuria support K. pneumoniae ST258 harboring blaKPC-3 being distributed throughout the Atlanta area, across the healthcare continuum. Overall mortality was high in this population, but the presence of carbapenemase genes was not associated with worse outcomes.
While gas-phase reactions and surface reactions on bare carbonaceous or siliceous dust grains contribute to cosmic chemistry, the energetic processing of cosmic ices via photochemistry and radiation chemistry is thought to be the dominant mechanism for the cosmic synthesis of prebiotic molecules. Because most previous laboratory astrochemical studies have used light sources that produce >10 eV photons and are, therefore, capable of ionizing cosmic ice analogs, discerning the role of photochemistry vs. radiation chemistry in astrochemistry is challenging. By using a source whose photon energy does not exceed 8 eV, we have studied ammonia and methanol cosmic ice reactions attributable solely to photochemistry. We compare these results to those obtained in the same ultrahigh vacuum chamber with 1 keV electrons which instead initiate radiation chemistry in cosmic ice analogs.
Studies using acute tryptophan depletion (ATD) to examine the effects of a rapid reduction in serotonin function have shown a reduction in global cognitive status during ATD in Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the severe cholinergic loss evident in dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD), we predicted that a reduction of global cognitive status during ATD would be greater in these conditions than in AD.
Methods:
Patients having DLB or PDD underwent ATD in a double-blind, placebo-controlled, randomized, counterbalanced, crossover design.
Results:
While the study intended to test 20 patients, the protocol was poorly tolerated and terminated after six patients attempted, but only four patients – three with DLB and one with PDD – completed the protocol. The Modified Mini-Mental State Examination (3MSE) score was reduced in all three DLB patients and unchanged in the PDD and dementia patient during ATD compared with placebo.
Conclusions:
This reduction in global cognitive function and the poor tolerability may fit with the hypothesis that people with dementia with Lewy bodies have sensitivity to the effects of reduced serotonin function.
The successful development of quantum computers is dependent on identifying quantum systems to function as qubits. Paramagnetic states of point defects in semiconductors or insulators have been shown to provide an effective implementation, with the nitrogen-vacancy center in diamond being a prominent example. The spin-1 ground state of this center can be initialized, manipulated, and read out at room temperature. Identifying defects with similar properties in other materials would add flexibility in device design and possibly lead to superior performance or greater functionality. A systematic search for defect-based qubits has been initiated, starting from a list of physical criteria that such centers and their hosts should satisfy. First-principles calculations of atomic and electronic structure are essential in supporting this quest: They provide a deeper understanding of defects that are already being exploited and allow efficient exploration of new materials systems and “defects by design.”
Objectives: The aim of this study was to describe the evolution of a cost-utility model used to inform the UK National Institute for Health and Clinical Excellence's (NICE) most recent decisions on the cost-utility of drug treatments for Alzheimer's disease (AD), and to explore the impact of structural assumptions on the cost-utility results.
Methods: Changes informed by noted limitations of the decision model used in NICE's previous decisions (in 2006) were made cumulatively to the original decision model for donepezil compared with best supportive care (for patients with mild to moderate AD). Deterministic and probabilistic analyses were undertaken for each cumulative change of the model. The expected value of perfect information (EVPI) of parameter estimates and structural assumptions was also calculated.
Results: Cumulative changes to the decision model highlighted how the results of the original model (incremental cost-effectiveness ratio of £81,000 per quality-adjusted life-year gained) related to those of the new model (where donepezil was estimated to be cost-saving), mainly due to uncertainty in the incremental cost of donepezil treatment over best supportive care (ranging from -£600 to £3,000 per patient). The partial EVPI analysis reflected this finding where further information on treatment discontinuations and cost parameter estimates were shown to be valuable in terms of reducing decision uncertainty.
Conclusions: Assessing the evolution of the cost-utility model helped to identify and explore structural differences between cohort-based models and is likely to be useful for decision models in other disease areas. This approach makes the structural uncertainty explicit, forcing decision makers to address structural uncertainty in addition to parameter uncertainty.