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Dying is mostly seen as a dreadful event, never a happy experience. Yet, as palliative care physicians, we have seen so many patients who remained happy despite facing death. Hence, we conducted this qualitative study to explore happiness in palliative care patients at the University of Malaya Medical Centre.
Twenty terminally ill patients were interviewed with semi-structured questions. The results were thematically analyzed.
Eight themes were generated: the meaning of happiness, connections, mindset, pleasure, health, faith, wealth, and work. Our results showed that happiness is possible at the end of life. Happiness can coexist with pain and suffering. Social connections were the most important element of happiness at the end of life. Wealth and work were given the least emphasis. From the descriptions of our patients, we recognized a tendency for the degree of importance to shift from the hedonic happiness to eudaimonic happiness as patients experienced a terminal illness.
Significance of results
To increase the happiness of palliative care patients, it is crucial to assess the meaning of happiness for each patient and the degree of importance for each happiness domain to allow targeted interventions.
High prevalence of insulin resistance (IR) has been reported in bipolar disorder (BD) patients. Importantly, impaired insulin sensitivity could modulate the course and treatment outcome in BD. Here, we hypothesized that insulin sensitivity could be potentially associated with the neurocognitive trajectory in euthymic BD. We aimed to examine differences in insulin sensitivity and executive function between BD patients and controls.
Sixty-two patients with BD receiving mood stabilizer treatment and 62 controls, matching age, sex, and body mass index, were recruited in this study. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The Wisconsin card-sorting test (WCST) was applied to test participants’ ability to shift cognitive set. Group differences were measured and multivariate regression analysis was performed to examine relationships among factors.
The results indicated that the HOMA-IR (P = .048) value in the patients with BD were significantly higher than those in controls. With regards to executive function, the BD patients performed significantly poorer than the control subjects (P < .05). Moreover, the interaction effect between BD diagnosis and HOMA-IR value on the WCST-preservation errors was significant (P = .01), and post-hoc analyses showed that the cognitive abilities were worse in the BD patients with a higher IR than in the others groups.
Insulin sensitivity is associated with the neurocognitive performance in euthymic BD patients. Although the underlying mechanisms remain unclear, interventions to improve insulin sensitivity could potentially improve the functional outcome of BD.
The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.
We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.
The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.
Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
ABSTRACT IMPACT: Understanding how spinal cord stimulation works and who it works best for will improve clinical trial efficacy and prevent unnecessary surgeries. OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for chronic low back pain where standard interventions fail to provide relief. However, estimates suggest only 58% of patients achieve at least 50% reduction in their pain. There is no non-invasive method for predicting relief provided by SCS. We hypothesize neural activity in the brain can fill this gap. METHODS/STUDY POPULATION: We tested SCS patients at 3 times points: baseline (pre-surgery), at day 7 during the trial period (post-trial), and 6 months after a permanent system had been implanted. At each time point participants completed 10 minutes of eyes closed, resting electroencephalography (EEG) and self-reported their pain. EEG was collected with the ActiveTwo system and a 128-electrode cap. Patients were grouped based on the percentage change of their pain from baseline to the final visit using a median split (super responders > average responders). Spectral density powerbands were extracted from resting EEG to use as input features for machine learning analyses. We used support vector machines to predict response to SCS. RESULTS/ANTICIPATED RESULTS: Baseline and post-trial EEG data predicted SCS response at 6-months with 95.56% and 100% accuracy, respectively. The gamma band had the highest performance in differentiating responders. Post-trial EEG data best differentiated the groups with feature weighted dipoles being more highly localized in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding how SCS works and who it works best for is the long-term objective of our collaborative research program. These data provide an important first step towards this goal.
Previous studies suggested that a disturbance of the dopamine system underlies the pathophysiology of bipolar disorder (BD). In addition, the therapeutic action of medications for treating BD, such as valproate (VPA), might modulate dopamine system activity, but it remains unclear. Here, we aimed to investigate the role of the striatal dopamine transporter (DAT) in BD patients and in social defeat (SD) mice treated with VPA.
We enrolled community-dwelling controls (N = 18) and BD patients (N = 23) who were treated with VPA in a euthymic stage. The striatal DAT availabilities were approached by TRODAT-1 single photon emission computed tomography. We also established a chronic SD mouse model and treated mice with 350 mg/kg VPA for 3 weeks. Behavioral tests were administered, and striatal DAT expression levels were determined.
In humans, the level of striatal DAT availability was significantly higher in euthymic BD patients (1.52 ± 0.17 and 1.37 ± 0.23, p = 0.015). Moreover, the level of striatal DAT availability was also negatively correlated with the VPA concentration in BD patients (r = −0.653, p = 0.003). In SD mice, the expression of striatal DAT significantly increased (p < 0.001), and the SD effect on DAT expression was rescued by VPA treatment.
The striatal DAT might play a role in the pathophysiology of BD and in the therapeutic mechanism of VPA. The homeostasis of DAT might represent a new therapeutic strategy for BD patients.
The development of microfabricated liquid cells has enabled dynamic studies of nanostructures within a liquid environment with electron microscopy. While such setups are most commonly found in transmission electron microscope (TEM) holders, their implementation in a scanning electron microscope (SEM) offers intriguing potential for multi-modal studies where the large chamber volume allows for the integration of multiple detectors. Here, we describe an electrochemical liquid cell SEM platform that employs the same cells enclosed by silicon nitride membrane windows found in liquid cell TEM holders and demonstrate the imaging of copper oxide nanoparticles in solution using both backscattered and transmitted electrons. In particular, the transmitted electron images collected at high scattering angles show contrast inversion at liquid layer thicknesses of several hundred nanometers, which can be used to determine the presence of liquid in the cell, while maintaining enough resolution to image nanoparticles that are tens of nanometers in size. Using Monte Carlo simulations, we show that both imaging modes have their advantages for liquid phase imaging and rationalize the contrast inversion observed in the transmitted electron image.
Overuse of antibiotics in the emergency department (ED) for uncomplicated acute respiratory tract infections (uARTIs) is a public health issue that needs to be addressed. We aimed to identify factors associated with antibiotic use for uARTIs in adults presenting at the ED.
We searched Medline, Embase, PsycINFO and the Cochrane Library for articles published from 1 January 2005 to 30 June 2017 using a predetermined search strategy. Titles and abstracts of English articles on antibiotic prescription and inappropriate antibiotic use for adult ARTI at EDs were assessed, followed by full article review, by 2 authors.
Adults aged 18 years and older.
Of the 2,591 articles retrieved, 12 articles met the inclusion criteria and 11 studies were conducted in the United States. Patients with normal C-reactive protein levels and positive influenza tests were less likely to receive antibiotic treatment. Nonclinical factors associated with antibiotic use were longer waiting time and perceived patient desire for antibiotics. Patients attended by internal medicine physicians comanaged by house staff or who visited an ED which provided education to healthcare providers on antibiotics use were less likely to receive antibiotics.
English-language articles that fulfilled the selection criteria outside the United States were limited. Factors associated with antibiotics use are multifaceted. Education of healthcare providers presents an opportunity to improve antibiotic use.
Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a major public health problem. Ceftazidime-avibactam (CZA) is a treatment option for CRE approved in 2015; however, it does not have activity against isolates with metallo-β-lactamases (MBLs). Emerging resistance to CZA is a cause for concern. Our objective was to describe the microbiologic and epidemiologic characteristics of CZA-resistant (CZA-R) CRE. Methods: From 2015 to 2017, 9 states participated in laboratory- and population-based surveillance for carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. aerogenes, and Enterobacter cloacae complex isolates from a normally sterile site or urine. A convenience sample of isolates from this surveillance were sent to the CDC for antimicrobial susceptibility testing (AST) using reference broth microdilution (BMD) including an MBL screen, species confirmation with MALDI-TOF, and real-time PCR to detect blaKPC, blaNDM, and blaOXA-48–like genes. Additional AST by BMD was performed on CZA-R isolates using meropenem-vaborbactam (MEV), imipenem-relebactam (IMR), plazomicin (PLZ), and eravacycline (ERV). Epidemiologic data were obtained from a medical record review. Community-associated cases were defined as having no healthcare exposures in the year prior to culture, no devices in place 2 days prior to culture, and culture collected before calendar day 3 after hospital admission. Data were analyzed in 3 groups: CRE that were CZA-susceptible (CZA-S), CZA-R that were due to blaNDM, and CZA-R without blaNDM. Results: Among 606 confirmed CRE tested with CZA, 33 (5.4%) were CZA-R. Of the CZA-R isolates, 16 (48.5%) harbored a blaNDM gene, of which 2 coharbored blaNDM and blaOXA-48-like genes; 9 (27.3%) harbored only a blaKPC gene. Of the 17 CZA-R isolates without blaNDM, all were MBL screen negative. CZA-R due to blaNDM were more frequently community-associated (43.8%) than CZA-S or CZA-R without blaNDM (11.0% and 5.9%, respectively); a higher percentage of CZA-R cases due to blaNDM also had recent international travel (25%) compared to the other groups (1.8% and 5.9%, respectively). CZA-R without blaNDM were more susceptible to MEV (76%), IMR (71%), PLZ (88%), and ERV (65%) compared to CZA-R due to blaNDM (19%, 6%, 56%, and 44%, respectively). Conclusions: The emergence of CZA-R isolates without blaNDM are concerning; however, these isolates are more susceptible to newer antimicrobials than those with blaNDM. In addition to high rates of resistance to newer antimicrobials, isolates with blaNDM are more frequently community-associated than other CRE. This underscores the need for more aggressive measures to stop the spread of CRE.
Background: In recent years, the historic declines in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in the United States have slowed. We examined trends in the incidence of community-onset (CO) MRSA BSIs among hospitalized persons with and without substance-use diagnoses. Methods: Using data from >200 US hospitals reporting to the Premier Healthcare Database (PHD) during 2012–2017, we conducted a retrospective study among hospitalized persons aged ≥18 years. MRSA BSIs with substance use were defined as hospitalizations having both a blood culture positive for MRSA and at least 1 International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) or ICD-10-CM diagnostic code for substance use including opioids, cocaine, amphetamines, or other substances (excluding cannabis, alcohol, and nicotine). MRSA BSIs were considered community onset when a positive blood culture was collected within 3 days of admission. We assessed annual trends and described characteristics of CO MRSA BSI hospitalizations, stratified by substance use. Results: Of 20,049 MRSA BSIs from 2012 to 2017, 17,634 (88%) were CO. Overall, MRSA BSI incidence decreased 7%, from 178.5 to 166.2 per 100,000 hospitalizations during the study period; However, CO MRSA BSI rates remained stable (152.7 to 149.9 per 100,000 hospitalizations). Among CO MRSA BSIs, 1,838 (10%) were BSIs with substance-use diagnoses; the incidence of CO MRSA BSIs with substance use increased 236% (from 8.2 to 27.6 per 100,000 hospitalizations) and represented a greater proportion of the CO MRSA rate over the study period (Fig. 1). The incidence of CO MRSA BSIs without substance use decreased 15% (from 144.5 to 122.4 per 100,000 hospitalizations). Patients with CO MRSA BSIs with substance use were younger (median, 40 vs 65 years), more likely to be female (50% vs 40%), white (79% vs 69%), and to leave against medical advice (15% vs 1%). Among patients not leaving against medical advice, CO BSI patients with substance-use diagnoses had longer lengths of stay (median, 11 vs 9 days), lower in-hospital mortality (9% vs 14%), and higher hospitalization costs (median, $22,912 vs $17,468) compared to patients without substance-use diagnoses. Conclusions: Although the overall CO MRSA BSI rate remained unchanged from 2012 to 2017, infections with substance use diagnoses increased >3-fold, and infections without substance use diagnoses decreased. These data suggest that the emergence of MRSA associated with substance-use diagnoses threatens potential progress in reducing the incidence of CO MRSA infections. Additional strategies may be needed to prevent MRSA BSI in patients with substance-use diagnoses, and to maintain national progress in the reduction of MRSA infections overall.
Background: The CDC has performed surveillance for invasive Staphylococcus aureus (iSA) infections through the Emerging Infections Program (EIP) since 2004. SCCmec and spa typing for clonal complex (CC) assignment and genomic markers have been used to characterize isolates. In 2019, whole-genome sequencing (WGS) of isolates began, allowing for high-resolution assessment of genomic diversity. Here, we evaluate the reliability of SCCmec typing, spa typing, and CC assignment using WGS data compared to traditional methods to ensure that backwards compatibility is maintained. Methods:S. aureus isolates were obtained from a convenience sample of iSA cases reported through the EIP surveillance system. Overall, 78 iSA isolates with diverse spa repeat patterns, CCs, SCCmec types, and antimicrobial susceptibility profiles were sequenced (MiSeq, Illumina). Real-time PCR and Sanger sequencing were used as the SCCmec and spa typing reference methods, respectively. spa-MLST mapping (Ridom SpaServer) served as the reference method for CC assignment. WGS assembly and multilocus sequence typing (MLST) were performed using the CDC QuAISAR-H pipeline. WGS-based MLST CCs were assigned using eBURST and SCCmec types using SCCmecFinder. spa types were assigned from WGS assemblies using BioNumerics. For isolate subtyping, previously published and validated canonical single-nucleotide polymorphisms (canSNPs) as well as the presence of the Panton-Valentine leukocidin (PVL) toxin and arginine catabolic mobile element (ACME) virulence factor were assessed for all genome assemblies. Results: All isolates were assigned WGS-based spa types, which were 100% concordant (78 of 78) with Sanger-based spa typing. SCCmecFinder assigned 91% of isolates (71 of 78) SCCmec types, which were 100% concordant with reference method results. Also, 7 isolates had multiple cassettes predicted or an incomplete SCCmec region assembly. Using WGS data, 96% (75 of 78) of isolates were assigned CCs; 3 isolates had unknown sequence types that were single-locus variants of established sequence types. Overall, 70 isolates had CCs assigned by the reference method; 100% (70 of 70) concordance was observed with WGS-based CCs. Analysis of canSNPs placed 42% (33 of 78) of isolates into CC8, with 17 (52%) of these isolates classified as USA300. PVL and ACME were not accurate markers for inferring the USA300 subtype as 24% (4 of 17) of isolates did not contain these markers. Conclusions:S. aureus CCs, SCCmec, and spa types can be reliably determined using WGS. Incorporation of canSNP analysis represents a more efficient method for CC8 assignment than the use of genomic markers alone. WGS allows for the replacement of multiple typing methods for increased laboratory efficiency, while maintaining backward compatibility with historical typing nomenclature.
Most invasive methicillin-resistant Staphylococcus aureus (iMRSA) infections have onset in the community but are associated with healthcare exposures. More than 25% of cases with healthcare exposure occur in nursing homes (NHs) where facility-specific iMRSA rates vary widely. We assessed associations between nursing home characteristics and iMRSA incidence rates to help target prevention efforts in NHs. Methods: We used active, laboratory- and population-based surveillance data collected through the Emerging Infections Program during 2011–2015 from 25 counties in 7 states. NH-onset cases were defined as isolation of MRSA from a normally sterile site in a surveillance area resident who was in a NH within 3 days before the index culture. We calculated MRSA incidence (cases per NH resident day) using Centers for Medicare & Medicaid Services (CMS) skilled nursing facility cost reports and described variation in iMRSA incidence by NH. We used Poisson regression with backward selection, assessing variables for collinearity, to estimate adjusted rate ratios (aRRs) for NH characteristics (obtained from the CMS minimum dataset) associated with iMRSA rates. Results: Of 590 surveillance area NHs included in analysis, 89 (15%) had no NH-onset iMRSA infections. Rates ranged from 0 to 23.4 infections per 100,000 resident days. Increased rate of NH-onset iMRSA infection occurred with increased percentage of residents in short stay ≤30 days (aRR, 1.09), exhibiting wounds or infection (surgical wound [aRR, 1.08]; vascular ulcer/foot infection [aRR, 1.09]; multidrug-resistant organism infection [aRR, 1.13]; receipt of antibiotics [aRR, 1.06]), using medical devices or invasive support (ostomy [aRR, 1.07]; dialysis [aRR, 1.07]; ventilator support [aRR, 1.17]), carrying neurologic diagnoses (cerebral palsy [aRR, 1.14]; brain injury [aRR, 1.1]), and demonstrating debility (requiring considerable assistance with bed mobility [aRR, 1.05]) (Table). iMRSA rates decreased with increased percentage of residents receiving influenza vaccination (aRR, 0.96) and with the presence of any patients in isolation for any active infection (aRR, 0.83). Conclusions: iMRSA incidence varies greatly across nursing homes, with many NH patient and facility characteristics associated with NH-onset iMRSA rate differences. Some associations (short stay, wounds and infection, medical device use and invasive support) suggest that targeted interventions utilizing known strategies to decrease transmission may help to reduce infection rates, while others (neurologic diagnoses, influenza vaccination, presence of patients in isolation) require further exploration to determine their role. These findings can help identify NHs in other areas more likely to have higher rates of NH-onset iMRSA who could benefit from interventions to reduce infection rates.
Background: Epidemiological studies have utilized administrative discharge diagnosis codes to identify methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA) infections and trends, despite debate regarding the accuracy of utilizing codes for this purpose. We assessed the sensitivity and positive predictive value (PPV) of MRSA- and MSSA-specific diagnosis codes, trends, characteristics, and outcomes of S. aureus hospitalizations by method of identification. Methods: Clinical micro biology results and discharge data from geographically diverse US hospitals participating in the Premier Healthcare Database from 2012–2017 were used to identify monthly rates of MRSA and MSSA. Positive MRSA or MSSA clinical cultures and/or a MRSA- or MSSA-specific International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10 CM) diagnosis codes from adult inpatients (aged ≥18 years) were included as S. aureus hospitalizations. Septicemia was defined as a positive blood culture or a MRSA or MSSA septicemia code. Sensitivity and PPV for codes were calculated for hospitalizations where admission status was not listed as transfer; true infection was considered a positive clinical culture. Negative binominal regression models measured trends in rates of MRSA and MSSA per 1,000 hospital discharges. Results: We identified 168,634 MRSA and 148,776 MSSA hospitalizations in 256 hospitals; 17% of MRSA and 21% of MSSA were septicemia. Less than half of all S. aureus hospitalizations (49% MRSA, 46% MSSA) and S. aureus septicemia hospitalizations (37% MRSA, 38% MSSA) had both a positive culture and diagnosis code (Fig. 1). Sensitivity of MRSA codes in identifying positive cultures was 61% overall and 56% for septicemia, PPV was 62% overall and 53% for septicemia. MSSA codes had a sensitivity of 49% in identifying MSSA cultures and 52% for MSSA septicemia; PPV was 69% overall and 62% for septicemia. Despite low sensitivity, MRSA trends are similar for cultures and codes, and MSSA trends are divergent (Fig. 2). For hospitalizations with septicemia, mortality was highest among those with a blood culture only (31.3%) compared to hospitalizations with both a septicemia code and blood culture (16.6%), and septicemia code only (14.7%). Conclusions: ICD diagnosis code sensitivity and PPV for identifying infections were consistently poor in recent years. Less than half of hospitalizations have concordant microbiology laboratory results and diagnosis codes. Rates and trend estimates for MSSA differ by method of identification. Using diagnosis codes to identify S. aureus infections may not be appropriate for descriptive epidemiology or assessing trends due to significant misclassification.
Disclosures: Scott Fridkin reports that his spouse receives consulting fees from the vaccine industry.
Background: Extended-spectrum β-lactamase–producing (ESBL) Escherichia coli infection incidence is increasing in the United States. This increase may be due to the rapid expansion of ST131, which is now the predominant ESBL strain globally, often multidrug resistant, and has been shown to establish longer-term human colonization than other E. coli strains. We assessed potential risk factors that distinguish ST131 from other ESBL E. coli. Methods: From October 1 through December 31, 2017, 5 CDC Emerging Infections Program (EIP) sites pilot tested active, laboratory-based surveillance in selected counties in Colorado, Georgia, New Mexico, New York, and Tennessee. An E. coli case was defined as the first isolation from a normally sterile body site or urine in a surveillance area resident in a 30-day period resistant to 1 extended-spectrum cephalosporin antibiotic and susceptible or intermediate to all carbapenem antibiotics tested. Epidemiologic data were collected from case patients’ medical records. A convenience sample of 117 E. coli isolates from case patients was collected. All isolates underwent whole-genome sequencing to determine sequence type and the presence of ESBL genes. We compared ST131 E. coli epidemiology to other ESBL E. coli. Results: Among 117 E. coli isolates, 97 (83%) were ESBL producers. Of the 97 ESBL E. coli, 52 (54%) were ST131 (range, for 4 EIP sites submitting >10 isolates: 25%–88%; P < .001). Other common STs were ST38 (12%) and ST10 (5%). ST131 infections were more likely to be healthcare-associated than non-ST131 (56% vs 36%; P = .05) (Table 1). Among specific prior healthcare exposures, only residence in long-term care facilities (LTCFs) in the year before culture was more common among ST131 case patients (29% vs 11%; P = .03). Notably, 85% of ESBL E. coli collected from LTCF residents were ST131. ST131 E. coli were more common among patients with underlying medical conditions (81% vs 60%; P = .02). No statistically significant difference by sex, race, age, culture source, location of culture collection, and frequency of antibiotic use in the prior 30 days was observed. Conclusions:The prevalence of ST131 E. coli varies regionally. The association between ST131 and LTCFs suggests that these may be particularly important settings for ST131 acquisition. Improving infection control measures that limit ESBL transmission in these settings and preventing dissemination in facilities receiving patients from LTCFs may be necessary to contain ST131 spread.
Background: Incidence of community-associated (CA) and healthcare-associated, community-onset (HACO) USA300 methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections has remained unchanged in recent years. Traditionally considered a CA strain, USA300 is increasingly associated with healthcare settings. We examined whether antimicrobial nonsusceptibility among USA300 strains could distinguish epidemiologic class (community vs hospital), and whether divergences in susceptibility were occurring over time. Methods: We used data on invasive MRSA infections from active, population, and laboratory-based surveillance during 2005–2016 from 11 counties in 3 states. Invasive cases were defined as MRSA isolation from a normally sterile site in a surveillance area resident. Cases were considered hospital-onset (HO) if the culture was obtained >3 days after hospitalization and HACO if ≥1 of the following risk factors was present: hospitalization, surgery, dialysis, or residence in a long-term care facility in the past year; or central vascular catheter ≤2 days before culture. Otherwise, cases were considered CA. Sites submitted a convenience sample of clinical MRSA isolates for molecular typing and antimicrobial susceptibility testing. Molecular typing was performed by pulsed-field gel electrophoresis until 2008, when typing was inferred using a validated algorithm based on molecular characteristics. Reference broth microdilution was performed for 8 antimicrobials and interpreted based on CLSI interpretive criteria. We compared USA300 nonsusceptibility for HO and CA isolates. For antimicrobials with >5% nonsusceptibility and for which HO isolates had greater nonsusceptibility than CA isolates, we compared nonsusceptibility for HACO and CA and analyzed annual trends in nonsusceptibility within each epidemiologic class (ie, CA, HACO, and HO) using linear regression. Results: Of 17,947 MRSA cases during 2005–2016, isolates were available for 6,685 (37%), and 2,120 were USA300 (34% CA, 52% HACO, 14% HO). HO isolates had more nonsusceptibility than CA isolates to gentamicin (2.2% vs 0.6%; P = .03), levofloxacin (47.8% vs 39.7%; P = .02), rifampin (3.7 vs 1.1%; P = .01), and trimethoprim-sulfamethoxazole (3.4% vs 0.6%; P = .04). HACO isolates also had more nonsusceptibility than CA isolates to levofloxacin (50.9% vs 39.7%; P < .01). Levofloxacin nonsusceptibility increased during 2005–2016 for HACO and CA isolates (P < .01), but not among HO isolates (P = .36) (Fig. 1). Conclusions: Overall, nonsusceptibility across drugs cannot distinguish USA300 isolates causing HO versus CA disease. Although HO isolates had higher levofloxacin nonsusceptibility than CA and HACO isolates early on, USA300 MRSA HACO isolates now have levofloxacin nonsusceptibility most similar to that of HO isolates. Further study could help to explore whether increases in fluoroquinolone nonsusceptibility among CA and HACO cases may be contributing to the persistence of USA300 strains.
Background: Extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-Ent) have emerged as a significant antimicrobial-resistance threat in the community in recent years. To better characterize ESBL-Ent in the community, we examined associations between community-associated ESBL-Ent incidence rates and area-based socioeconomic status (SES) characteristics. Methods: Cases were identified through active, laboratory- and population-based surveillance for ESBL-Ent in 3 Emerging Infections Program (EIP) sites (New Mexico, New York, and Tennessee) from October through December 2017. We defined a case as first isolation of Escherichia coli, Klebsiella pneumoniae, or K. oxytoca from a normally sterile body specimen or urine in a surveillance-site resident, with resistance to ≥1 extended-spectrum cephalosporin and nonresistance to all carbapenems tested. Epidemiologic data were abstracted from medical records. Cases were considered community associated if no significant prior healthcare exposures (ie, inpatient healthcare facility stay, surgery, chronic dialysis, indwelling devices, or external catheters) were documented. Case residential addresses were geocoded and linked to US Census Bureau data to obtain census-tract level SES measures. Census tracts were dichotomized by the percentage living in rural areas (0–49% or ≥50%); census tracts were stratified into quartiles for all other characteristics. Incidence rate ratios (IRR) for each measure, controlling for EIP site, were calculated using Poisson regression. Results: Among 742 ESBL-Ent cases with medical records available, 355 (47.1%) were community associated; of these, 327 case addresses (92.1%) were successfully geocoded. The combined annualized 2017 incidence rate for community-associated ESBL-Ent was 83.2 cases per 100,000 persons. The highest incidence of community-associated ESBL-Ent was seen in census tracts with the lowest median income (IRR, 1.4; 95% CI, 1.0–2.0) and with the highest percentages of persons without health insurance (IRR, 1.3; 95% CI, 1.0–1.7), with <12th-grade education (IRR, 1.5; 95% CI, 1.1–2.1), living in urban areas (IRR, 1.5; 95% CI, 1.0–2.2), foreign-born (IRR, 1.4; 95% CI, 1.0–2.0), or speaking limited English (IRR, 1.5; 95% CI, 1.1–2.0). There were no significant differences across quartiles for population density, income inequality, the percentage of the population living below poverty, or the percentage of households with crowding (>1 occupant or room). Conclusions: Social determinants of health, such as coverage for healthcare, appear to be important contributors to community-associated ESBL-Ent transmission. Higher rates in areas with more foreign-born persons and persons with limited English proficiency suggest a role for recent travel in importation and spread in specific communities. These findings provide additional information about the epidemiology of ESBL-Ent in the community and have potential implications for control efforts.
OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for patients with chronic back pain. Technological advances have led to renewed optimism in the field, but mechanisms of action in the brain remain poorly understood. We hypothesize that SCS outcomes will be associated with changes in neural oscillations. METHODS/STUDY POPULATION: The goal of our team project is to test patients who receive SCS at 3 times points: baseline, at day 7 during the trial period, and day 180 after a permanent system has been implanted. At each time point participants will complete 10 minutes of eyes closed, resting electroencephalography (EEG). EEG will be collected with the ActiveTwo system, a 128-electrode cap, and a 256 channel AD box from BioSemi. Traditional machine learning methods such as support vector machine and more complex models including deep learning will be used to generate interpretable features within resting EEG signals. RESULTS/ANTICIPATED RESULTS: Through machine learning, we anticipate that SCS will have a significant effect on resting alpha and beta power in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: This collaborative project will further the application of machine learning in cognitive neuroscience and allow us to better understand how therapies for chronic pain alter resting brain activity.
It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.
Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.
DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.
The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
The present study examined the relationship between the Lie scale scores and striatal D2/D3 receptor availability with respect to the cerebellum in 42 healthy community volunteers in Taiwan using single photon emission computed tomography (SPECT) with [123I]iodo-benzoaminde (IBZM). Even after controlling of age and educational level, subjects' Lie scale scores of the Maudsley personality inventory correlate negatively with D2/D3 receptor availability. Individual with higher Lie scale scores may have higher impulsivity due to lower dopaminergic availability.