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Due to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance.
Large academic medical center.
We performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998–2005) and the postimplementation period (2006–2016).
Large rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005–1.072), E. cloacae (RR, 1.028; 95% CI, 1.013–1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006–1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996–1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975–0.987).
A stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.
Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.
In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.
After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).
PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.
The patterns of comorbidity among mental disorders have led researchers to model the underlying structure of psychopathology. While studies have suggested a structure including internalizing and externalizing disorders, less is known with regard to the cross-national stability of this model. Moreover, little data are available on the placement of eating disorders, bipolar disorder and psychotic experiences (PEs) in this structure.
We evaluated the structure of mental disorders with data from the World Health Organization Composite International Diagnostic Interview, including 15 lifetime mental disorders and six PEs. Respondents (n = 5478–15 499) were included from 10 high-, middle- and lower middle-income countries across the world aged 18 years or older. Confirmatory factor analyses (CFAs) were used to evaluate and compare the fit of different factor structures to the lifetime disorder data. Measurement invariance was evaluated with multigroup CFA (MG-CFA).
A second-order model with internalizing and externalizing factors and fear and distress subfactors best described the structure of common mental disorders. MG-CFA showed that this model was stable across countries. Of the uncommon disorders, bipolar disorder and eating disorder were best grouped with the internalizing factor, and PEs with a separate factor.
These results indicate that cross-national patterns of lifetime common mental-disorder comorbidity can be explained with a second-order underlying structure that is stable across countries and can be extended to also cover less common mental disorders.
The interaction of radio frequency waves with charged particles in a magnetized plasma is usually described by the quasilinear operator that was originally formulated by Kennel & Engelmann (Phys. Fluids, vol. 9, 1966, pp. 2377–2388). In their formulation the plasma is assumed to be homogenous and embedded in a uniform magnetic field. In tokamak plasmas the Kennel–Engelmann operator does not capture the magnetic drifts of the particles that are inherent to the non-uniform magnetic field. To overcome this deficiency a combined drift and gyrokinetic derivation is employed to derive the quasilinear operator for radio frequency heating and current drive in a tokamak with magnetic drifts retained. The derivation requires retaining the magnetic moment to higher order in both the unperturbed and perturbed kinetic equations. The formal prescription for determining the perturbed distribution function then follows a novel procedure in which two non-resonant terms must be evaluated explicitly. The systematic analysis leads to a diffusion equation that is compact and completely expressed in terms of the drift kinetic variables. The equation is not transit averaged, and satisfies the entropy principle, while retaining the full poloidal angle variation without resorting to Fourier decomposition. As the diffusion equation is in physical variables, it can be implemented in any computational code. In the Kennel–Engelmann formalism, the wave–particle resonant delta function is either for the Landau resonance or the Doppler shifted cyclotron resonance. In the combined gyro and drift kinetic approach, a term related to the magnetic drift modifies the resonance condition.
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
Channels incised into bedrock, or Nye channels, often form an important component of subglacial drainage at temperate glaciers, and their structure exerts control over patterns and rates of (a) channel erosion, (b) water flow-velocity and (c) water pressure. The latter, in turn, exerts a strong control over basal traction and, thus, ice dynamics. In order to investigate these controls, it is necessary to quantify detailed flow processes in subglacial Nye channels. However, it is effectively impossible to acquire such measurements from fully pressurized, subglacial channels. To solve this problem, we here apply a three-dimensional, finite-volume solution of the Reynolds averaged Navier– Stokes (RANS) equations with a one-equation mixing-length turbulence closure to simulate flow in a 3 m long section of an active Nye channel located in the immediate foreground of Glacier de Tsanfleuron, Switzerland. Numerical model output permits high-resolution visualization of water flow through the channel reach, and enables evaluation of the experimental manipulation of the pressure field adopted across the overlying ice lid. This yields an increased theoretical understanding of the hydraulic behaviour of Nye channels, and, in the future, of their effect on glacier drainage, geomorphology and ice dynamics.
Patients with cardiovascular diseases are common in the emergency department (ED), and continuity of care following that visit is needed to ensure that they receive evidence-based diagnostic tests and therapy. We examined the frequency of follow-up care after discharge from an ED with a new diagnosis of one of three cardiovascular diseases.
We performed a retrospective cohort study of patients with a new diagnosis of heart failure, atrial fibrillation, or hypertension, who were discharged from 157 non-pediatric EDs in Ontario, Canada, between April 2007 and March 2014. We determined the frequency of follow-up care with a family physician, cardiologist, or internist within seven and 30 days, and assessed the association of patient, emergency physician, and family physician characteristics with obtaining follow-up care using cause-specific hazard modeling.
There were 41,485 qualifying ED visits. Just under half (47.0%) had follow-up care within seven days, with 78.7% seen by 30 days. Patients with serious comorbidities (renal failure, dementia, COPD, stroke, coronary artery disease, and cancer) had a lower adjusted hazard of obtaining 7-day follow-up care (HRs 0.77-0.95) and 30-day follow-up care (HR 0.76-0.95). The only emergency physician characteristic associated with follow-up care was 5-year emergency medicine specialty training (HR 1.11). Compared to those whose family physician was remunerated via a primarily fee-for-service model, patients were less likely to obtain 7-day follow-up care if their family physician was remunerated via three types of capitation models (HR 0.72, 0.81, 0.85) or via traditional fee-for-service (HR 0.91). Findings were similar for 30-day follow-up care.
Only half of patients discharged from an ED with a new diagnosis of atrial fibrillation, heart failure, and hypertension were seen within a week of being discharged. Patients with significant comorbidities were less likely to obtain follow-up care, as were those with a family physician who was remunerated via primarily capitation methods.
Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.
To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).
Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).
Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.
Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
We describe new conversion laws, from CO molecular line data to inferred mass column, based on observations of the three main CO isotopologues in several surveys of the Galactic Plane. The new conversion laws replace the use of the single “X-factor” in widespread use, with a more physically-based relationship between the CO line’s optical depth, excitation, and column density. It has the effect of increasing the inferred mass column, over the single X-factor, by typically a factor of 2–3. This means that the molecular mass of the Milky Way may have been substantially underestimated in previous studies, and suggests that scaling laws like the Kennicutt-Schmidt relations may also need to be recalibrated. Because of its statistical basis on a large fraction of our Galaxy’s ISM, this new law is also recommended for use in studies of other Milky-Way-analogue spiral galaxies.
Surgical site infections (SSIs) are responsible for significant morbidity and mortality. Preadmission skin antisepsis, while controversial, has gained acceptance as a strategy for reducing the risk of SSI. In this study, we analyze the benefit of an electronic alert system for enhancing compliance to preadmission application of 2% chlorhexidine gluconate (CHG).
DESIGN, SETTING, AND PARTICIPANTS
Following informed consent, 100 healthy volunteers in an academic, tertiary care medical center were randomized to 5 chlorhexidine gluconate (CHG) skin application groups: 1, 2, 3, 4, or 5 consecutive applications. Participants were further randomized into 2 subgroups: with or without electronic alert. Skin surface concentrations of CHG (μg/mL) were analyzed using a colorimetric assay at 5 separate anatomic sites.
Preadmission application of chlorhexidine gluconate, 2%
Mean composite skin surface CHG concentrations in volunteer participants receiving EA following 1, 2, 3, 4, and 5 applications were 1,040.5, 1,334.4, 1,278.2, 1,643.9, and 1,803.1 µg/mL, respectively, while composite skin surface concentrations in the no-EA group were 913.8, 1,240.0, 1,249.8, 1,194.4, and 1,364.2 µg/mL, respectively (ANOVA, P<.001). Composite ratios (CHG concentration/minimum inhibitory concentration required to inhibit the growth of 90% of organisms [MIC90]) for 1, 2, 3, 4, or 5 applications using the 2% CHG cloth were 208.1, 266.8, 255.6, 328.8, and 360.6, respectively, representing CHG skin concentrations effective against staphylococcal surgical pathogens. The use of an electronic alert system resulted in significant increase in skin concentrations of CHG in the 4- and 5-application groups (P<.04 and P<.007, respectively).
The findings of this study suggest an evidence-based standardized process that includes use of an Internet-based electronic alert system to improve patient compliance while maximizing skin surface concentrations effective against MRSA and other staphylococcal surgical pathogens.
Infect. Control Hosp. Epidemiol. 2016;37(3):254–259
Non-right handedness (NRH) is reportedly more common in very preterm (VPT; <32 weeks’ gestation) children compared with term-born peers, but it is unclear whether neonatal brain injury or altered brain morphology and microstructure underpins NRH in this population. Given that NRH has been inconsistently reported to be associated with cognitive and motor difficulties, this study aimed to examine associations between handedness and neurodevelopmental outcomes in VPT 7-year-olds. Furthermore, the relationship between neonatal brain injury and integrity of motor tracts (corpus callosum and corticospinal tract) with handedness at age 7 years in VPT children was explored. One hundred seventy-five VPT and 69 term-born children completed neuropsychological and motor assessments and a measure of handedness at 7 years’ corrected age. At term-equivalent age, brain injury on MRI was assessed and diffusion tensor measures were obtained for the corpus callosum and posterior limb of the internal capsule. There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] −1.95, 95% confidence interval [−5.67, 1.77]). Poorer academic and working memory outcomes were associated with stronger NRH in the VPT group. While there was little evidence that neonatal unilateral brain injury was associated with stronger NRH, increased area and fractional anisotropy of the corpus callosum splenium were predictive of stronger NRH in the VPT group. VPT birth may alter the relationship between handedness and academic outcomes, and neonatal corpus callosum integrity predicts hand preference in VPT children at school age. (JINS, 2015, 21, 610–621)
The scalable storage of renewable energy by means of converting water to hydrogen fuels electrochemically hinges on fundamental improvements in catalytic materials. However, many applications exist where an extended lifetime is virtually crucial for their functionality and success, e.g. in case of limited accessibility such as tire pressure sensors or biomedical implants. For these kinds of applications, the ultimate power supply should be a self-renewing energy source. This strategy is pursued by the concept of Micro Energy Harvesting (MEH). Within a MEH system a micro generator converts ambient energy to electrical energy for driving an application. Unfortunately, it is not ensured that the ambient energy level will maintain always high enough to provide sufficient power to the system as harvested energy usually manifests itself in rather irregular, random and low-energy bursts. One appealing form of integrated energy storage is the use of H2/air, a so called fuel cell type (FC) battery. Such devices promise very high volumetric energy densities of more than 2000 Wh/l. Consequently, this type of battery has recently attracted more and more attention and primary as well as secondary cells have been realized. Alkaline polymer electrolyte fuel cells have been recognized as the most promising solution in order to overcome the dependency on noble metal catalysts. Nevertheless, further improvements for these kinds of fuel cells have to be reached with respect to high power. Therefore, one promising approach is to increase the skin surface of porous chromium decorated nickel electrodes for enhancement of exchange current density by forming three-dimensional (3D) microstructures directly into the electrode. Therefore, a novel laser structuring process was applied using ultrashort laser pulses. Ultrashort laser processing of complex multimaterial systems for energy storage allow for precise material removal without changing the material properties. By applying this novel laser-based structuring technique, 3D microstructures could be formed permitting shortened diffusion lengths between the electrolyte and the electrode surface being necessary for increased exchange current densities.
Immediate-release (IR) quetiapine has been used to treat schizophrenia since 1997, although all the principal placebo-controlled trials have >50% missing outcome data. New studies with relatively lower rates of participant withdrawal have since been published.
To assess the efficacy and adverse effects of quetiapine IR for schizophrenia, with consideration of outcome quality and clinical meaningfulness of results, and to examine the potential impact of missing data on the main efficacy findings.
We conducted a systematic review and meta-analysis of randomised controlled trials comparing quetiapine IR and placebo (or subtherapeutic dose in relapse prevention trials) for the treatment of schizophrenia (PROSPERO registration CRD4201100165). Primary outcomes were change in overall symptoms and response rates. We also examined whether high rates of participant withdrawal (⩾50%) attenuated effect sizes, and assessed the impact of making different assumptions about these people's outcomes.
We identified 15 relevant trials (including 2 unpublished), providing the first 12-week data for this drug and the first data on self-reported quality of life. We found quetiapine IR to have a weighted mean difference (WMD) of 6.5 points (95% CI −8.9 to −4) on Positive and Negative Syndrome Scale (PANSS) total scores, which corresponds to a standardised mean difference (SMD) of −0.33 (95% CI −0.46 to −0.21). Longer trials reported larger mean differences favouring quetiapine IR, but the overall estimate was smaller if more conservative assumptions about the outcomes of people who left the trial early were made. Approximately 21 people needed to take quetiapine IR for 1 person to experience at least a 50% improvement in PANSS score. No difference in quality of life was observed (two RCTs), although small to moderate improvements in social functioning were found (three RCTs). Quetiapine IR caused sedation and increased rates of clinically significant weight gain, but no extrapyramidal effects were observed.
Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2–12 weeks, but also leads to weight gain and sedation.