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Whole-genome sequencing (WGS) shotgun metagenomics (metagenomics) attempts to sequence the entire genetic content straight from the sample. Diagnostic advantages lie in the ability to detect unsuspected, uncultivatable, or very slow-growing organisms.
Objective:
To evaluate the clinical and economic effects of using WGS and metagenomics for outbreak management in a large metropolitan hospital.
Design:
Cost-effectiveness study.
Setting:
Intensive care unit and burn unit of large metropolitan hospital.
Patients:
Simulated intensive care unit and burn unit patients.
Methods:
We built a complex simulation model to estimate pathogen transmission, associated hospital costs, and quality-adjusted life years (QALYs) during a 32-month outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). Model parameters were determined using microbiology surveillance data, genome sequencing results, hospital admission databases, and local clinical knowledge. The model was calibrated to the actual pathogen spread within the intensive care unit and burn unit (scenario 1) and compared with early use of WGS (scenario 2) and early use of WGS and metagenomics (scenario 3) to determine their respective cost-effectiveness. Sensitivity analyses were performed to address model uncertainty.
Results:
On average compared with scenario 1, scenario 2 resulted in 14 fewer patients with CRAB, 59 additional QALYs, and $75,099 cost savings. Scenario 3, compared with scenario 1, resulted in 18 fewer patients with CRAB, 74 additional QALYs, and $93,822 in hospital cost savings. The likelihoods that scenario 2 and scenario 3 were cost-effective were 57% and 60%, respectively.
Conclusions:
The use of WGS and metagenomics in infection control processes were predicted to produce favorable economic and clinical outcomes.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The target article presents strong empirical evidence that knowledge is basic. However, it offers an unsatisfactory account of what makes knowledge basic. Some current ideas in cognitive neuroscience – predictive coding and analysis by synthesis – point to a more plausible account that better explains the evidence.
This manuscript describes the institutional and clinical considerations that apply to the question of whether to mandate opioid dose reduction in patients who have received opioids long-term. It describes how a calamitous rise in addiction and overdose involving opioids has both led to a clinical recalibration by healthcare providers, and to strong incentives favoring forcible opioid reduction by policy making agencies. Neither the 2016 Guideline issued by the Centers for Disease Control and Prevention nor clinical evidence can justify or promote such policies as safe or effective.
As approximately one-third of peer-victimized children evidence heightened aggression (Schwartz, Proctor, & Chien, 2001), it is imperative to identify the circumstances under which victimization and aggression co-develop. The current study explored two potential moderators of victimization–aggression linkages: (a) attentional bias toward cues signaling threat and (b) attentional bais toward cues communicating interpersonal support. Seventy-two fifth- and sixth-grade children (34 boys; Mage = 11.67) were eye tracked while watching video clips of bullying. Each scene included a bully, a victim, a reinforcer, and a defender. Children's victimization was measured using peer, parent, and teacher reports. Aggression was measured using peer reports of overt and relational aggression and teacher reports of aggression. Victimization was associated with greater aggression at high levels of attention to the bully. Victimization was also associated with greater aggression at low attention to the defender for boys, but at high attention to the defender for girls. Attention to the victim was negatively correlated with aggression regardless of victimization history. Thus, attentional biases to social cues integral to the bullying context differentiate whether victimization is linked to aggression, necessitating future research on the development of these biases and concurrent trajectories of sociobehavioral development.
This article reviews the most likely mechanisms of transmission of the commonly encountered respiratory viruses (influenza, respiratory syncytial virus, parainfluenza, rhinovirus), herpesviruses, and hepatitis viruses, and presents the guidelines used currently for prevention and control that are in use at Strong Memorial Hospital.
North American studies show bipolar disorder is associated with elevated
rates of problem gambling; however, little is known about rates in the
different presentations of bipolar illness.
Aims
To determine the prevalence and distribution of problem gambling in
people with bipolar disorder in the UK.
Method
The Problem Gambling Severity Index was used to measure gambling problems
in 635 participants with bipolar disorder.
Results
Moderate to severe gambling problems were four times higher in people
with bipolar disorder than in the general population, and were associated
with type 2 disorder (OR = 1.74, P = 0.036), history of
suicidal ideation or attempt (OR = 3.44, P = 0.02) and
rapid cycling (OR = 2.63, P = 0.008).
Conclusions
Approximately 1 in 10 patients with bipolar disorder may be at moderate
to severe risk of problem gambling, possibly associated with suicidal
behaviour and a rapid cycling course. Elevated rates of gambling problems
in type 2 disorder highlight the probable significance of modest but
unstable mood disturbance in the development and maintenance of such
problems.
To identify the source of a pseudo-outbreak of Mycobacterium gordonae
DESIGN
Outbreak investigation.
SETTING
University Hospital in Chicago, Ilinois.
PATIENTS
Hospital patients with M. gordonae-positive clinical cultures.
METHODS
An increase in isolation of M. gordonae from clinical cultures was noted immediately following the opening of a newly constructed hospital in January 2012. We reviewed medical records of patients with M. gordonae-positive cultures collected between January and December 2012 and cultured potable water specimens in new and old hospitals quantitatively for mycobacteria.
RESULTS
Of 30 patients with M. gordonae-positive clinical cultures, 25 (83.3%) were housed in the new hospital; of 35 positive specimens (sputum, bronchoalveolar lavage, gastric aspirate), 32 (91.4%) had potential for water contamination. M. gordonae was more common in water collected from the new vs. the old hospital [147 of 157 (93.6%) vs. 91 of 113 (80.5%), P=.001]. Median concentration of M. gordonae was higher in the samples from the new vs. the old hospital (208 vs. 48 colony-forming units (CFU)/mL; P<.001). Prevalence and concentration of M. gordonae were lower in water samples from ice and water dispensers [13 of 28 (46.4%) and 0 CFU/mL] compared with water samples from patient rooms and common areas [225 of 242 (93%) and 146 CFU/mL, P<.001].
CONCLUSIONS
M. gordonae was common in potable water. The pseudo-outbreak of M. gordonae was likely due to increased concentrations of M. gordonae in the potable water supply of the new hospital. A silver ion-impregnated 0.5-μm filter may have been responsible for lower concentrations of M. gordonae identified in ice/water dispenser samples. Hospitals should anticipate that construction activities may amplify the presence of waterborne nontuberculous mycobacterial contaminants.
Poly(3,4-ethylenedioxythiophene) (PEDOT) was polymerized with the biological dopants dextran sulphate and chondroitin sulphate. Polymer physical and mechanical properties were investigated using quartz crystal microgravimetry with dissipation monitoring and atomic force microscopy, revealing polymer shear modulus and interfacial roughness to be significantly altered as a function of the dopant species. The adsorption of fibronectin, an important extracellular protein that is critical for a range of cellular functions and processes, was investigated using QCM-D, revealing protein adsorption to be increased on the DS doped PEDOT film relative to the CS doped film. PEDOT films have traditionally been doped with synthetic counterions such as polystyrene sulphonate (PSS), however the incorporation of biological molecules as the counterion, which has been shown to improve polymer biofunctionality, has received far less attention. In particular, there has been little detailed study on the impact of incorporating polyelectrolyte biomolecules into the PEDOT polymer matrix on fundamental polymer properties which are critical for biomedical applications. This investigation provides a detailed characterization of the interfacial and mechanical properties of biologically doped PEDOT films, as well as the efficacy of the composite films to bind and retain extracellular proteins of the type that are critical to the biocompatibility of the polymeric material.