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To describe national trends in testing and detection of carbapenemases
produced by carbapenem-resistant Enterobacterales (CRE) and associate
testing with culture and facility characteristics.
Design:
Retrospective cohort study.
Setting:
Department of Veterans’ Affairs medical centers (VAMCs).
Participants:
Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE,
defined by national VA guidelines.
Interventions:
Microbiology and clinical data were extracted from national VA data sets.
Carbapenemase testing was summarized using descriptive statistics.
Characteristics associated with carbapenemase testing were assessed with
bivariate analyses.
Results:
Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of
molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had
carbapenemases detected. Among these cultures confirmed as
carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for
≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC
detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other
enzymes was less frequent. Carbapenemase testing increased over the study
period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US
Census region (38.6%) and the Northeast (37.2%) region had the highest
proportion of CRE cultures with carbapenemase testing. High complexity (vs
low) and urban (vs rural) facilities were significantly associated with
carbapenemase testing (P < .0001).
Conclusions:
Between 2013 and 2018, carbapenemase testing and detection increased in the
VA, largely reflecting increased testing and detection of KPC. Surveillance
of other carbapenemases is important due to global spread and increasing
antibiotic resistance. Efforts supporting the expansion of carbapenemase
testing to low-complexity, rural healthcare facilities and standardization
of reporting of carbapenemase testing are needed.
Virtual reality has emerged as a unique educational modality for medical trainees. However, incorporation of virtual reality curricula into formal training programmes has been limited. We describe a multi-centre effort to develop, implement, and evaluate the efficacy of a virtual reality curriculum for residents participating in paediatric cardiology rotations.
Methods:
A virtual reality software program (“The Stanford Virtual Heart”) was utilised. Users are placed “inside the heart” and explore non-traditional views of cardiac anatomy. Modules for six common congenital heart lesions were developed, including narrative scripts. A prospective case–control study was performed involving three large paediatric residency programmes. From July 2018 to June 2019, trainees participating in an outpatient cardiology rotation completed a 27-question, validated assessment tool. From July 2019 to February 2020, trainees completed the virtual reality curriculum and assessment tool during their cardiology rotation. Qualitative feedback on the virtual reality experience was also gathered. Intervention and control group performances were compared using univariate analyses.
Results:
There were 80 trainees in the control group and 52 in the intervention group. Trainees in the intervention group achieved higher scores on the assessment (20.4 ± 2.9 versus 18.8 ± 3.8 out of 27 questions answered correctly, p = 0.01). Further analysis showed significant improvement in the intervention group for questions specifically testing visuospatial concepts. In total, 100% of users recommended integration of the programme into the residency curriculum.
Conclusions:
Virtual reality is an effective and well-received adjunct to clinical curricula for residents participating in paediatric cardiology rotations. Our results support continued virtual reality use and expansion to include other trainees.
Understanding how cardiovascular structure and physiology guide management is critically important in paediatric cardiology. However, few validated educational tools are available to assess trainee knowledge. To address this deficit, paediatric cardiologists and fellows from four institutions collaborated to develop a multimedia assessment tool for use with medical students and paediatric residents. This tool was developed in support of a novel 3-dimensional virtual reality curriculum created by our group.
Methods:
Educational domains were identified, and questions were iteratively developed by a group of clinicians from multiple centres to assess understanding of key concepts. To evaluate content validity, content experts completed the assessment and reviewed items, rating item relevance to educational domains using a 4-point Likert scale. An item-level content validity index was calculated for each question, and a scale-level content validity index was calculated for the assessment tool, with scores of ≥0.78 and ≥0.90, respectively, representing excellent content validity.
Results:
The mean content expert assessment score was 92% (range 88–97%). Two questions yielded ≤50% correct content expert answers. The item-level content validity index for 29 out of 32 questions was ≥0.78, and the scale-level content validity index was 0.92. Qualitative feedback included suggestions for future improvement. Questions with ≤50% content expert agreement and item-level content validity index scores <0.78 were removed, yielding a 27-question assessment tool.
Conclusions:
We describe a multi-centre effort to create and validate a multimedia assessment tool which may be implemented within paediatric trainee cardiology curricula. Future efforts may focus on content refinement and expansion to include additional educational domains.
To examine the association between adherence to plant-based diets and mortality.
Design:
Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods.
Setting:
The VA Million Veteran Program.
Participants:
315 919 men and women aged 19–104 years who completed a FFQ at the baseline.
Results:
We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, Ptrend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, Ptrend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, Ptrend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.
Conclusions:
A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.
Among 108 (0.05% of cohort) US veterans with a Clostridioides difficile infection (CDI) within 30 days of a dental antibiotic prescription, 80% of patients received guideline-discordant antibiotics. Half had chronic gastrointestinal illness potentially exacerbating their CDI risk. More efforts are needed to improve antibiotic stewardship.
Borderline personality disorder (BPD) is a mental health condition characterized by emotion dysregulation, interpersonal impairment, and high suicidality. Dialectical behaviour therapy (DBT) is the most widely studied psychotherapeutic treatment for BPD. To date, the vast majority of DBT research has focused on cisgender women, with a notable lack of systematic investigation of sex and/or gender differences in treatment response. In order to encourage effective, equitable treatment of BPD, further investigation into treatment targets in this population is critical. Here, we employed a systematic strategy to delineate gaps in the DBT literature pertaining to sex and gender differences and propose directions for future research. Findings demonstrate a significant discrepancy in measurement of sex and gender, particularly among gender-diverse individuals. Exploring DBT treatment response across the full spectrum of genders will facilitate the provision of more tailored, impactful care to all individuals who suffer from BPD.
Key learning aims
(1) To date, DBT treatment literature has focused almost exclusively on cisgender women, with only two of 253 DBT studies in current literature accounting for transgender and gender diverse (TGD) individuals.
(2) Recognize how gender minority stress may impact the prevalence of BPD among TGD individuals.
(3) Learn how future research initiatives can be employed to rectify this gap in the DBT literature.
Racial disparities in colorectal cancer (CRC) can be addressed through increased adherence to screening guidelines. In real-life encounters, patients may be more willing to follow screening recommendations delivered by a race concordant clinician. The growth of telehealth to deliver care provides an opportunity to explore whether these effects translate to a virtual setting. The primary purpose of this pilot study is to explore the relationships between virtual clinician (VC) characteristics and CRC screening intentions after engagement with a telehealth intervention leveraging technology to deliver tailored CRC prevention messaging.
Methods:
Using a posttest-only design with three factors (VC race-matching, VC gender, intervention type), participants (N = 2267) were randomised to one of eight intervention treatments. Participants self-reported perceptions and behavioral intentions.
Results:
The benefits of matching participants with a racially similar VC trended positive but did not reach statistical significance. Specifically, race-matching positively influenced screening intentions for Black participants but not for Whites (b = 0.29, p = 0.10). Importantly, perceptions of credibility, attractiveness, and message relevance significantly influenced screening intentions and the relationship with race-matching.
Conclusions:
To reduce racial CRC screening disparities, investments are needed to identify patient-focused interventions to address structural barriers to screening. This study suggests that telehealth interventions that match Black patients with a Black VC can enhance perceptions of credibility and message relevance, which may then improve screening intentions. Future research is needed to examine how to increase VC credibility and attractiveness, as well as message relevance without race-matching.
Two introduced carnivores, the European red fox Vulpes vulpes and domestic cat Felis catus, have had extensive impacts on Australian biodiversity. In this study, we collate information on consumption of Australian birds by the fox, paralleling a recent study reporting on birds consumed by cats. We found records of consumption by foxes on 128 native bird species (18% of the non-vagrant bird fauna and 25% of those species within the fox’s range), a smaller tally than for cats (343 species, including 297 within the fox’s Australian range, a subset of that of the cat). Most (81%) bird species eaten by foxes are also eaten by cats, suggesting that predation impacts are compounded. As with consumption by cats, birds that nest or forage on the ground are most likely to be consumed by foxes. However, there is also some partitioning, with records of consumption by foxes but not cats for 25 bird species, indicating that impacts of the two predators may also be complementary. Bird species ≥3.4 kg were more likely to be eaten by foxes, and those <3.4 kg by cats. Our compilation provides an inventory and describes characteristics of Australian bird species known to be consumed by foxes, but we acknowledge that records of predation do not imply population-level impacts. Nonetheless, there is sufficient information from other studies to demonstrate that fox predation has significant impacts on the population viability of some Australian birds, especially larger birds, and those that nest or forage on the ground.
Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a carbapenem antibiotic (M/V and I/R) with a β-lactamase inhibitor. They are used to treat carbapenem-resistant Enterobacterales (CRE) and/or multidrug-resistant Pseudomonas aeruginosa (MDRPA).
Objective:
We compared the pooled clinical success of these medications to older therapies.
Methods:
PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for C/A, C/T, I/R, and M/V studies. The main outcome was clinical success, which was assessed using random-effects models. Stratified analyses were conducted for study drug, sample size, quality, infection source, study design, and multidrug-resistant gram-negative organism (MDRGNO) population. Microbiological success and 28- and 30-day mortality were assessed as secondary outcomes. Heterogeneity was determined using I2 values.
Results:
Overall, 25 articles met the inclusion criteria; 8 observational studies and 17 randomized control trials. We detected no difference in clinical success comparing new combination antibiotics with standard therapies for all included organisms (pooled OR, 1.21; 95% CI, 0.96–1.51). We detected a moderate level of heterogeneity among the included studies I2 = 56%. Studies that focused on patients with CRE or MDRPA infections demonstrated a strong association between treatment with new combination antibiotics and clinical success (pooled OR, 2.20; 95% CI, 1.60–3.57).
Conclusions:
C/T, C/A, I/R, and M/V are not inferior to standard therapies for treating various complicated infections, but they may have greater clinical success for treating MDRPA and CRE infections. More studies that evaluate the use of these antibiotics for drug-resistant infections are needed to determine their effectiveness.
We assessed trends in treatment of patients with CRE from 2012 through 2018. We detected decreased utilization of aminoglycosides and colistin and increased utilization in extended-spectrum cephalosporins and ceftazidime-avibactam. We found significant uptake of ceftazidime-avibactam, a newly approved antibiotic, to treat CRE infections.
This is an epidemiological study of carbapenem-resistant Enterobacteriaceae (CRE) in Veterans’ Affairs medical centers (VAMCs). In 2017, almost 75% of VAMCs had at least 1 CRE case. We observed substantial geographic variability, with more cases in urban, complex facilities. This supports the benefit of tailoring infection control strategies to facility characteristics.
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.
Although infections caused by Acinetobacter baumannii are often healthcare-acquired, difficult to treat, and associated with high mortality, epidemiologic data for this organism are limited. We describe the epidemiology, clinical characteristics, and outcomes for patients with extensively drug-resistant Acinetobacter baumannii (XDRAB).
Design:
Retrospective cohort study
Setting:
Department of Veterans’ Affairs Medical Centers (VAMCs)
Participants:
Patients with XDRAB cultures (defined as nonsusceptible to at least 1 agent in all but 2 or fewer classes) at VAMCs between 2012 and 2018.
Methods:
Microbiology and clinical data was extracted from national VA datasets. We used descriptive statistics to summarize patient characteristics and outcomes and bivariate analyses to compare outcomes by culture source.
Results:
Among 11,546 patients with 15,364 A. baumannii cultures, 408 (3.5%) patients had 667 (4.3%) XDRAB cultures. Patients with XDRAB were older (mean age, 68 years; SD, 12.2) with median Charlson index 3 (interquartile range, 1–5). Respiratory specimens (n = 244, 36.6%) and urine samples (n = 187, 28%) were the most frequent sources; the greatest proportion of patients were from the South (n = 162, 39.7%). Most patients had had antibiotic exposures (n = 362, 88.7%) and hospital or long-term care admissions (n = 331, 81%) in the prior 90 days. Polymyxins, tigecycline, and minocycline demonstrated the highest susceptibility. Also, 30-day mortality (n = 96, 23.5%) and 1-year mortality (n = 199, 48.8%) were high, with significantly higher mortality in patients with blood cultures.
Conclusions:
The proportion of Acinetobacter baumannii in the VA that was XDR was low, but treatment options are extremely limited and clinical outcomes were poor. Prevention of healthcare-associated XDRAB infection should remain a priority, and novel antibiotics for XDRAB treatment are urgently needed.
Decisions to treat large-vessel occlusion with endovascular therapy (EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ comorbidities. We explored EVT/alteplase decision-making by stroke experts in the setting of comorbidity/disability.
Methods:
In an international multi-disciplinary survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case scenarios. Five included comorbidities (cancer, cardiac/respiratory/renal disease, mild cognitive impairment [MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions.
Results:
Among 607 physicians (38 countries), EVT was chosen less often in comorbidity-related scenarios (79.6% under current resources, 82.7% assuming ideal conditions) versus six “level-1A” scenarios for which EVT/alteplase was clearly indicated by current guidelines (91.1% and 95.1%, respectively, odds ratio [OR] [current resources]: 0.38, 95% confidence interval 0.31–0.47). However, EVT was chosen more often in comorbidity-related scenarios compared to all other 17 scenarios (79.6% versus 74.4% under current resources, OR: 1.34, 1.17–1.54). Responses favoring alteplase for comorbidity-related scenarios (e.g. 75.0% under current resources) were comparable to level-1A scenarios (72.2%) and higher than all others (60.4%). No comorbidity independently diminished EVT odds when considering all scenarios. MCI and dependence carried higher alteplase odds; cancer and cardiac/respiratory/renal disease had lower odds. Being older/female carried lower EVT odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT-, lower alteplase odds), practicing in East Asia (higher EVT odds), and in interventional neuroradiology (lower alteplase odds vs neurology).
Conclusion:
Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT. Differences in decision-making by patient age/sex merit further study.
We discuss a family of Vlasov–Maxwell equilibrium distribution functions for current sheet equilibria that are intermediate cases between the Harris sheet and the force-free (or modified) Harris sheet. These equilibrium distribution functions have potential applications to space and astrophysical plasmas. The existence of these distribution functions had been briefly discussed by Harrison & Neukirch (Phys. Rev. Lett., vol. 102, (2009a), 135003), but here it is shown that their approach runs into problems in the limit where the guide field goes to zero. The nature of this problem will be discussed and an alternative approach will be suggested that avoids the problem. This is achieved by considering a slight variation of the magnetic field profile, which allows a smooth transition between the Harris and force-free Harris sheet cases.
Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is an amphetamine derivative that is used recreationally and is now being tested in clinical trials for treatment of posttraumatic stress disorder. Ecstasy can damage serotonin neurones in brain of experimental animals; however, relevance of these findings to the human is debated.
Aim:
To measure by positron emission tomography (PET) levels of binding to the serotonin transporter (SERT), a marker of serotonin neurones, in brain of chronic ecstasy users and in matched controls.
Methods:
An estimate of brain SERT levels was obtained, using the PET tracer 11C-DASB, in 50 chronic (confirmed by drug hair testing) ecstasy users (mean age, 26 years; mean duration of drug use, 3.9 years; median drug withdrawal time, 38 days) and 50 (drug-hair negative) control subjects (mean age 26 years).
Results:
SERT binding levels in the ecstasy group were significantly decreased by 22 to 46% in frontal, temporal, cingulate, insular and occipital cortices, and by 23% in hippocampus. However, concentrations were distinctly normal in the SERT-rich caudate, putamen, ventral striatum and thalamus.
Conclusion:
Our imaging data suggest that cerebral cortical SERT concentration is below normal in some ecstasy users for at least one month after last use of the drug. However, it remains to be established whether low SERT might have preceded drug use, reflects actual loss of brain serotonin neurones, or is causally related to any functional impairment in the ecstasy users. (Supported by US NIH NIDA DA017301).
Between 2010 and 2019 the international health care organization Partners In Health (PIH) and its sister organization Zanmi Lasante (ZL) mounted a long-term response to the 2010 Haiti earthquake, focused on mental health. Over that time, implementing a Theory of Change developed in 2012, the organization successfully developed a comprehensive, sustained community mental health system in Haiti's Central Plateau and Artibonite departments, directly serving a catchment area of 1.5 million people through multiple diagnosis-specific care pathways. The resulting ZL mental health system delivered 28 184 patient visits and served 6305 discrete patients at ZL facilities between January 2016 and September 2019. The experience of developing a system of mental health services in Haiti that currently provides ongoing care to thousands of people serves as a case study in major challenges involved in global mental health delivery. The essential components of the effort to develop and sustain this community mental health system are summarized.
In a tertiary-care hospital and affiliated long-term care facility, a stewardship intervention focused on patients with Clostridioides difficile infection (CDI) was associated with a significant reduction in unnecessary non-CDI antibiotic therapy. However, there was no significant reduction in total non-CDI therapy or in the frequency of CDI recurrence.