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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).
Retrospective cohort study
Department of Veterans’ Affairs Medical Centers (VAMCs)
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.
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.
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.
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.
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.
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).
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.
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.
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).
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.
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).
This study examined the long-term effects of a randomized controlled trial of the Family Check-Up (FCU) intervention initiated at age 2 on inhibitory control in middle childhood and adolescent internalizing and externalizing problems. We hypothesized that the FCU would promote higher inhibitory control in middle childhood relative to the control group, which in turn would be associated with lower internalizing and externalizing symptomology at age 14. Participants were 731 families, with half (n = 367) of the families assigned to the FCU intervention. Using an intent-to-treat design, results indicate that the FCU intervention was indirectly associated with both lower internalizing and externalizing symptoms at age 14 via its effect on increased inhibitory control in middle childhood (i.e., ages 8.5–10.5). Findings highlight the potential for interventions initiated in toddlerhood to have long-term impacts on self-regulation processes, which can further reduce the risk for behavioral and emotional difficulties in adolescence.
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.
Meal timing may influence food choices, neurobiology and psychological states. Our exploratory study examined if time-of-day eating patterns were associated with mood disorders among adults.
During 2004–2006 (age 26–36 years) and 2009–2011 (follow-up, age 31–41 years), N = 1304 participants reported 24-h food and beverage intake. Time-of-day eating patterns were derived by principal components analysis. At follow-up, the Composite International Diagnostic Interview measured lifetime mood disorder. Log binomial and adjacent categories log-link regression were used to examine bidirectional associations between eating patterns and mood disorder. Covariates included sex, age, marital status, social support, education, work schedule, body mass index and smoking.
Three patterns were derived at each time-point: Grazing (intake spread across the day), Traditional (highest intakes reflected breakfast, lunch and dinner), and Late (skipped/delayed breakfast with higher evening intakes). Compared to those in the lowest third of the respective pattern at baseline and follow-up, during the 5-year follow-up, those in the highest third of the Late pattern at both time-points had a higher prevalence of mood disorder [prevalence ratio (PR) = 2.04; 95% confidence interval (CI) 1.20–3.48], and those in the highest third of the Traditional pattern at both time-points had a lower prevalence of first onset mood disorder (PR = 0.31; 95% CI 0.11–0.87). Participants who experienced a mood disorder during follow-up had a 1.07 higher relative risk of being in a higher Late pattern score category at follow-up than those without mood disorder (95% CI 1.00–1.14).
Non-traditional eating patterns, particularly skipped or delayed breakfast, may be associated with mood disorders.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Building on prior work using Tom Dishion's Family Check-Up, the current article examined intervention effects on dysregulated irritability in early childhood. Dysregulated irritability, defined as reactive and intense response to frustration, and prolonged angry mood, is an ideal marker of neurodevelopmental vulnerability to later psychopathology because it is a transdiagnostic indicator of decrements in self-regulation that are measurable in the first years of life that have lifelong implications for health and disease. This study is perhaps the first randomized trial to examine the direct effects of an evidence- and family-based intervention, the Family Check-Up (FCU), on irritability in early childhood and the effects of reductions in irritability on later risk of child internalizing and externalizing symptomatology. Data from the geographically and sociodemographically diverse multisite Early Steps randomized prevention trial were used. Path modeling revealed intervention effects on irritability at age 4, which predicted lower externalizing and internalizing symptoms at age 10.5. Results indicate that family-based programs initiated in early childhood can reduce early childhood irritability and later risk for psychopathology. This holds promise for earlier identification and prevention approaches that target transdiagnostic pathways. Implications for future basic and prevention research are discussed.
Kochia is one of the most problematic weeds in the United States. Field studies were conducted in five states (Wyoming, Colorado, Kansas, Nebraska, and South Dakota) over 2 yr (2010 and 2011) to evaluate kochia control with selected herbicides registered in five common crop scenarios: winter wheat, fallow, corn, soybean, and sugar beet to provide insight for diversifying kochia management in crop rotations. Kochia control varied by experimental site such that more variation in kochia control and biomass production was explained by experimental site than herbicide choice within a crop. Kochia control with herbicides currently labeled for use in sugar beet averaged 32% across locations. Kochia control was greatest and most consistent from corn herbicide programs (99%), followed by soybean (96%) and fallow (97%) herbicide programs. Kochia control from wheat herbicide programs was 93%. With respect to the availability of effective herbicide options, glyphosate-resistant kochia control was easiest in corn, soybean, and fallow, followed by wheat; and difficult to manage with herbicides in sugar beet.
The ALMA twenty-six arcmin2 survey of GOODS-S at one millimeter (ASAGAO) is a deep (1σ ∼ 61μJy/beam) and wide area (26 arcmin2) survey on a contiguous field at 1.2 mm. By combining with archival data, we obtained a deeper map in the same region (1σ ∼ 30μJy/beam−1, synthesized beam size 0.59″ × 0.53″), providing the largest sample of sources (25 sources at 5σ, 45 sources at 4.5σ) among ALMA blank-field surveys. The median redshift of the 4.5σ sources is 2.4. The number counts shows that 52% of the extragalactic background light at 1.2 mm is resolved into discrete sources. We create IR luminosity functions (LFs) at z = 1–3, and constrain the faintest luminosity of the LF at 2 < z < 3. The LFs are consistent with previous results based on other ALMA and SCUBA-2 observations, which suggests a positive luminosity evolution and negative density evolution.
Introduction: Acute aortic syndrome (AAS) is a time sensitive aortic catastrophe that is often misdiagnosed. There are currently no Canadian guidelines to aid in diagnosis. Our goal was to adapt the existing American Heart Association (AHA) and European Society of Cardiology (ESC) diagnostic algorithms for AAS into a Canadian evidence based best practices algorithm targeted for emergency medicine physicians. Methods: We chose to adapt existing high-quality clinical practice guidelines (CPG) previously developed by the AHA/ESC using the GRADE ADOLOPMENT approach. We created a National Advisory Committee consisting of 21 members from across Canada including academic, community and remote/rural emergency physicians/nurses, cardiothoracic and cardiovascular surgeons, cardiac anesthesiologists, critical care physicians, cardiologist, radiologists and patient representatives. The Advisory Committee communicated through multiple teleconference meetings, emails and a one-day in person meeting. The panel prioritized questions and outcomes, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations. The algorithm was prepared and revised through feedback and discussions and through an iterative process until consensus was achieved. Results: The diagnostic algorithm is comprised of an updated pre test probability assessment tool with further testing recommendations based on risk level. The updated tool incorporates likelihood of an alternative diagnosis and point of care ultrasound. The final best practice diagnostic algorithm defined risk levels as Low (0.5% no further testing), Moderate (0.6-5% further testing required) and High ( >5% computed tomography, magnetic resonance imaging, trans esophageal echocardiography). During the consensus and feedback processes, we addressed a number of issues and concerns. D-dimer can be used to reduce probability of AAS in an intermediate risk group, but should not be used in a low or high-risk group. Ultrasound was incorporated as a bedside clinical examination option in pre test probability assessment for aortic insufficiency, abdominal/thoracic aortic aneurysms. Conclusion: We have created the first Canadian best practice diagnostic algorithm for AAS. We hope this diagnostic algorithm will standardize and improve diagnosis of AAS in all emergency departments across Canada.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=−2·30+0·17x) (95 % CI −0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.
So far, only one distribution function giving rise to a collisionless nonlinear force-free current sheet equilibrium allowing for a plasma beta less than one is known (Allanson et al., Phys. Plasmas, vol. 22 (10), 2015, 102116; Allanson et al., J. Plasma Phys., vol. 82 (3), 2016a, 905820306). This distribution function can only be expressed as an infinite series of Hermite functions with very slow convergence and this makes its practical use cumbersome. It is the purpose of this paper to present a general method that allows us to find distribution functions consisting of a finite number of terms (therefore easier to use in practice), but which still allow for current sheet equilibria that can, in principle, have an arbitrarily low plasma beta. The method involves using known solutions and transforming them into new solutions using transformations based on taking integer powers (
) of one component of the pressure tensor. The plasma beta of the current sheet corresponding to the transformed distribution functions can then, in principle, have values as low as
. We present the general form of the distribution functions for arbitrary
and then, as a specific example, discuss the case for