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Cerebrospinal fluid shunt–associated surgical site infection surveillance for 3 months compared to 12 months after surgery captures 83% of cases with no significant differences in patient characteristics, surgery types, or pathogens. A shorter 3-month follow-up can reduce resource use and allow for more timely reporting of healthcare-associated infection rates for hospitals.
Suicide is the second leading cause of death in all youth and among adults with bipolar disorder (BD). The risk of suicide in BD is among the highest of all psychiatric conditions. Self-harm, including suicide attempts and non-suicidal self-injury, is a leading risk factor for suicide. Neuroimaging studies suggest reward circuits are implicated in both BD and self-harm; however, studies have yet to examine self-harm related resting-state functional connectivity (rsFC) phenotypes within adolescent BD.
Resting-state fMRI data were analyzed for 141 adolescents, ages 13–20 years, including 38 with BD and lifetime self-harm (BDSH+), 33 with BD and no self-harm (BDSH−), and 70 healthy controls (HC). The dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC) and amygdala were examined as regions of interest in seed-to-voxel analyses. A general linear model was used to explore the bivariate correlations for each seed.
BDSH− had increased positive rsFC between the left amygdala and left lateral occipital cortex, and between the right dlPFC and right frontal pole, and increased negative rsFC between the left amygdala and left superior frontal gyrus compared to BDSH+ and HC. BDSH+ had increased positive rsFC of the right OFC with the precuneus and left paracingulate gyrus compared to BDSH− and HC.
This study provides preliminary evidence of altered reward-related rsFC in relation to self-harm in adolescents with BD. Between-group differences conveyed a combination of putative risk and resilience connectivity patterns. Future studies are warranted to evaluate changes in rsFC in response to treatment and related changes in self-harm.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
To determine the frequency and predictors of antibiotic escalation in response to the inpatient sepsis screen at our institution.
Retrospective cohort study.
Two affiliated academic medical centers in Los Angeles, California.
Hospitalized patients aged 18 years and older who had their first positive sepsis screen between January 1, 2019, and December 31, 2019, on acute-care wards.
We described the rate and etiology of antibiotic escalation, and we conducted multivariable regression analyses of predictors of antibiotic escalation.
Of the 576 cases with a positive sepsis screen, antibiotic escalation occurred in 131 cases (22.7%). New infection was the most documented etiology of escalation, with 76 cases (13.2%), followed by known pre-existing infection, with 26 cases (4.5%). Antibiotics were continued past 3 days in 17 cases (3.0%) in which new or existing infection was not apparent. Abnormal temperature (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.91–4.70) and abnormal lactate (aOR, 2.04; 95% CI, 1.28–3.27) were significant predictors of antibiotic escalation. The patient already being on antibiotics (aOR, 0.54; 95% CI, 0.34–0.89) and the positive screen occurred during a nursing shift change (aOR, 0.36; 95% CI, 0.22–0.57) were negative predictors. Pneumonia was the most documented new infection, but only 19 (50%) of 38 pneumonia cases met full clinical diagnostic criteria.
Inpatient sepsis screening led to a new infectious diagnosis in 13.2% of all positive sepsis screens, and the risk of prolonged antibiotic exposure without a clear infectious source was low. Pneumonia diagnostics and lactate testing are potential targets for future stewardship efforts.
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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.
SARS-CoV-2, which causes the disease COVID-19, generally has a mild disease course in children. However, a severe post-infectious inflammatory process known as multisystem inflammatory syndrome in children has been observed in association with COVID-19. This inflammatory process is a result of an abnormal immune response with similar clinical features to Kawasaki disease. It is well established that multisystem inflammatory syndrome in children is associated with myocardial dysfunction, coronary artery dilation or aneurysms, and occasionally arrhythmias. The most common electrocardiographic abnormalities seen include premature atrial or ventricular ectopy, variable degrees of atrioventricular block, and QTc prolongation, and rarely, haemodynamically significant arrhythmias necessitating extracorporeal membrane oxygenation support. However, presentation with fever, hypotension, and relative bradycardia with a left axis idioventricular rhythm has not been previously reported. We present a case of a young adolescent with multisystem inflammatory syndrome in children with myocarditis and a profoundly inappropriate sinus node response to shock with complete resolution following intravenous immunoglobulin.
The authors surveyed hospitals across the country on their policies regarding overlapping surgery, and found large variation between hospitals in how this practice is regulated. Specifically, institutions chose to define “critical portions” in a variety of ways, ultimately affecting not only surgical efficiency but also the autonomy of surgical trainees and patient experiences at these different hospitals.
Fetal and neonatal alloimmune thrombocytopenia (AIT) is the most common cause of severe thrombocytopenia in fetuses and neonates . Maternal IgG alloantibodies against paternally derived fetal platelet antigens cross the placenta early in pregnancy and commonly result in severe thrombocytopenia. While the reported incidence varies somewhat with the assigned threshold of thrombocytopenia (50, 100, or 150 × 109/L), in most unselected populations AIT affects 1 in 1,000 live births. Table 14.1 displays the studies of AIT in unselected populations, systematically screened. In its severe form, AIT has the potential for significant morbidity (including intracranial hemorrhage in utero) and mortality. In milder forms, there are either antibodies with no thrombocytopenia, or mild to moderate thrombocytopenia, which is identified only by a complete blood count obtained for another indication or in a screening study. While there have been extensive efforts made in the diagnosis and characterization of the disease, strategies for early detection and intervention remain controversial.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Toxoplasma gondii (T. gondii) is an important human disease-causing parasite. In the USA, T. gondii infects >10% of the population, accrues economic losses of US$3.6 billion/year, and ranks as the second leading culprit of foodborne illness-related fatalities. We assessed toxoplasmosis risk among the Old Order Amish, a mostly homogenous population with a high prevalence of T. gondii seropositivity, using a questionnaire focusing on food consumption/preparation behaviours and environmental risk factors. Analyses were conducted using multiple logistic regression. Consuming raw meat, rare meat, or unpasteurised cow or goat milk products was associated with increased odds of seropositivity (unadjusted Odds Ratios: 2.192, 1.613, and 1.718 , respectively). In separate models by sex, consuming raw meat, or consuming unpasteurised cow or goat milk products, was associated with increased odds of seropositivity among women; washing hands after touching meat with decreased odds of seropositivity among women (adjusted OR (AOR): 0.462); and cleaning cat litterbox with increased odds of seropositivity among men (AOR: 5.241). This is the first study to assess associations between behavioural and environmental risk factors and T. gondii seropositivity in a US population with high seroprevalence for T. gondii. Our study emphasises the importance of proper food safety behaviours to avoid the risk of infection.
Precise instrumental calibration is of crucial importance to 21-cm cosmology experiments. The Murchison Widefield Array’s (MWA) Phase II compact configuration offers us opportunities for both redundant calibration and sky-based calibration algorithms; using the two in tandem is a potential approach to mitigate calibration errors caused by inaccurate sky models. The MWA Epoch of Reionization (EoR) experiment targets three patches of the sky (dubbed EoR0, EoR1, and EoR2) with deep observations. Previous work in Li et al. (2018) and (2019) studied the effect of tandem calibration on the EoR0 field and found that it yielded no significant improvement in the power spectrum (PS) over sky-based calibration alone. In this work, we apply similar techniques to the EoR1 field and find a distinct result: the improvements in the PS from tandem calibration are significant. To understand this result, we analyse both the calibration solutions themselves and the effects on the PS over three nights of EoR1 observations. We conclude that the presence of the bright radio galaxy Fornax A in EoR1 degrades the performance of sky-based calibration, which in turn enables redundant calibration to have a larger impact. These results suggest that redundant calibration can indeed mitigate some level of model incompleteness error.
Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk.
Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12–30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions.
Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval.
This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.
To make a power spectrum (PS) detection of the 21-cm signal from the Epoch of Reionisation (EoR), one must avoid/subtract bright foreground sources. Sources such as Fornax A present a modelling challenge due to spatial structures spanning from arc seconds up to a degree. We compare modelling with multi-scale (MS) CLEAN components to ‘shapelets’, an alternative set of basis functions. We introduce a new image-based shapelet modelling package, SHAMFI. We also introduce a new CUDA simulation code (WODEN) to generate point source, Gaussian, and shapelet components into visibilities. We test performance by modelling a simulation of Fornax A, peeling the model from simulated visibilities, and producing a residual PS. We find the shapelet method consistently subtracts large-angular-scale emission well, even when the angular resolution of the data is changed. We find that when increasing the angular resolution of the data, the MS CLEAN model worsens at large angular scales. When testing on real Murchison Widefield Array data, the expected improvement is not seen in real data because of the other dominating systematics still present. Through further simulation, we find the expected differences to be lower than obtainable through current processing pipelines. We conclude shapelets are worthwhile for subtracting extended galaxies, and may prove essential for an EoR detection in the future, once other systematics have been addressed.
To outline features of the neurologic examination that can be performed virtually through telemedicine platforms (the virtual neurological examination [VNE]), and provide guidance for rapidly pivoting in-person clinical assessments to virtual visits during the COVID-19 pandemic and beyond.
The full neurologic examination is described with attention to components that can be performed virtually.
A screening VNE is outlined that can be performed on a wide variety of patients, along with detailed descriptions of virtual examination maneuvers for specific scenarios (cognitive testing, neuromuscular and movement disorder examinations).
During the COVID-19 pandemic, rapid adoption of virtual medicine will be critical to provide ongoing and timely neurological care. Familiarity and mastery of a VNE will be critical for neurologists, and this article outlines a practical approach to implementation.
What have scholars learned over the past decade about the forces that shape the creation, design, and adaptation of intergovernmental institutions in earth system governance and their influence on state behaviour? Context characteristics – shared, science-based knowledge; the behaviours involved; and the availability of alternative behaviours – can shape institutional creation, design and adaptation. The strategies states, existing institutions and non-state actors deploy, in turn, can promote institutional formation despite challenges or inhibit it despite propitious conditions. Context characteristics also can pose larger or smaller obstacles to institutional effectiveness. Institutions prove more effective when their designs reflect political, economic and social constraints as well as major actors’ power and incentives. They shape material, ideational and normative incentives and opportunities that channel states toward positive behaviours and away from negative ones. New research can build on recent findings by investigating complex interactions at and across the international, transnational, domestic and subnational levels of earth system governance.