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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Comprehend, Cope and Connect (CCC) is a trauma-informed, transdiagnostic and evidence-based psychological intervention for mental health crises that can be applied cross-culturally. CCC has been implemented in acute and crisis mental health settings across the South of England and in services elsewhere in the UK. More recently, it has been taken up and adapted for specialist community settings, including perinatal services, addiction services and primary care settings. A continuously growing evidence base indicates that CCC could be the next step towards solving the national problem of mental health crises. It is now time for CCC to be piloted and researched nationally.
Point-of-care ultrasound (POCUS) is a tool frequently used in emergency medicine practice. POCUS is the medical use of ultrasound technology at the bedside for evaluation of acute medical conditions in patient care. POCUS can be a useful adjunct in observation units (OUs) for patients who require longer observation periods than can be accommodated during an acute emergency department (ED) stay. We describe three clinical scenarios in which POCUS could help assess patients in OUs who have a change in clinical condition: focused assessment by sonography in trauma (FAST) POCUS exams, congestive heart failure – cardiac and lung ultrasound, and syncope – cardiac ultrasound.
Sudden cardiac death is a significant concern among patients with congenital heart disease (CHD). We assessed the risk of remote sudden cardiac death after congenital heart surgery.
Methods:
Patients undergoing congenital heart surgery before 21 years of age between 1982 and 2003 in the Pediatric Cardiac Care Consortium registry were linked to National Death Index data through 2019. Sudden cardiac death was defined as death associated with a cardiac arrest or ventricular fibrillation diagnosis code. Standardised mortality ratios relative to the general population were calculated using Centers for Disease Control and Prevention data.
Results:
Among 30,566 patients discharged after their initial surgery, 2,718 deaths occurred over a median period of 23 years (IQR 19–27). Of 463 (17%) sudden cardiac deaths, the median age was 1.7 years (IQR 0.5–16.5). The mean incidence was 7 per 10,000 person-years (95% CI: 0.64–0.77), ranging from 2.7 for left-to-right shunt lesions to 37 for single-ventricle physiology. Cardiac comorbidities including heart failure (13.6%) and arrhythmias (7.1%) were more frequent among sudden cardiac death patients. Standard mortality ratios for sudden cardiac death were elevated across all CHD types, ranging from 8.0 (95% CI: 6.3–9.6) for left-to-right shunts to 107.7 (95% CI: 88.9–126.5) for single-ventricle physiology.
Conclusion:
Sudden cardiac death risk is higher post-congenital heart surgery compared to the general population. Even patients with mild CHD are at risk, highlighting the need for long-term follow-up for all patients. Heart failure and arrhythmia prevalence suggest potential therapeutic targets to reduce sudden cardiac death risk.
The viability of small island developing states (SIDS) is threatened by three distinct processes – a backlash against globalisation; rising geopolitical competition between powers; and accelerating climate change – which are pulling at the threads binding the liberal international order together. We suggest that this order has been kinder to SIDS than is often acknowledged because its underpinning norms – sovereign equality, non-interference, and right to development – are inherently permissive and thus provide SIDS with choices rather than imperatives. Their leaders should fight for the continuation and enhancement of that order rather than be seduced by alternatives. We provide a rationale for and examples of policies to achieve this, including reforms to the way ODA is measured, debt restructured, climate finance allocated, and global governance organised. These enhancements represent the most plausible pathway for SIDS in a period of significant global upheaval. This title is also available as Open Access on Cambridge Core.
The use of clozapine demands regular monitoring of patients’ clozapine blood levels. Assays are usually performed in a central laboratory with results available only after several days. The South London and Maudsley NHS Trust wanted to implement a clozapine Point-of-Care (POC) capillary blood test that would provide the benefits of immediate results.
Methods
The MyCare Insite, a small (2.2 kg) tabletop analyser was used. The Insite can readily be connected to electronic health records. Insite device has been fully validated but to achieve the benefit of clozapine POC testing, other factors beyond the test validation needed to be considered. We developed tools, software, and processes to guide health professionals on why and when to measure clozapine blood levels, on what to do with test results, and systems for documentation and tracking of patients’ test results. In addition, the device supplier conducted staff training to ensure consistent and correct testing. Finally, users were certified as qualified based on demonstrated proficiency.
Results
We have fully implemented POC capillary clozapine testing across four geographic sites.. Patients and staff preferred capillary finger stick testing over venous draws. Patients’ engagement with their results was better than with laboratory testing. Real-time testing for adherence was possible for patients admitted on clozapine. It was also possible to make rapid dose adjustments based on near immediate plasma level results. Patient safety was increased since toxic levels could be quickly detected. Clinical decision-making was expedited as results were available immediately (< 7 minutes). The utility of the testing meant that the length of hospital stays was reduced as discharges were not delayed pending a laboratory result.
Conclusion
Clozapine POC blood level testing was successfully implemented at our institution achieving the expected benefits of clozapine POC testing with near immediate results. The new process improves clozapine management, patient engagement and reduces inpatient bed stays.
People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.
Methods:
We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.
Results:
Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.
Conclusions:
CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
OBJECTIVES/GOALS: In triple negative breast cancer (TNBC), obesity is associated with poor outcomes. Adipose stem cells (ASCs) from obese patients (obASCs) secrete higher levels of adipokines compared to ASCs from lean individuals. Leptin, one of these adipokines, has been implicated in many cancers. This study seeks to examine the role of leptin signaling in TNBC. METHODS/STUDY POPULATION: Previous work in conjunction with a collaborating lab has shown that leptin signaling promotes metastasis and increased expression of epithelial-mesenchymal transition (EMT) markers in triple negative breast cancer cell lines. This project expands upon this work through using both patient-derived cell lines and and patient-derived xenografts (PDX), and examines the role of leptin signaling both in vitro and in vivo. To determine the effects of obesity upon a PDX model of TNBC, a high fat diet was used to induce obesity in vivo. A pharmacological inhibitor of the leptin receptor was used to test the requirement for leptin signaling both in vivo and in vitro. RESULTS/ANTICIPATED RESULTS: Exposure to conditioned media harvested from obASCs increased the percentage of TNBC cells that expressed cancer stem cell markers, whereas exposure to an inhibitor of the leptin receptor decreased the percentage of cells with cancer stem cell markers. PDX tumors implanted into mice with diet-induced obesity had an increased volume compared to tumors implanted into lean controls. Further analysis will be conducted on metastasis, circulating tumor cells, and survival in both lean and obese mice. DISCUSSION/SIGNIFICANCE: Understanding the complex signaling events in the obese tumor microenvironment is essential, as these molecular differences may contribute to different outcomes for obese and lean individuals with triple negative breast cancer. Therefore, study of the crosstalk between obASCs and TNBC cells is critical.
Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.
Methods
MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.
Results
VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.
Conclusions
Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.
To determine whether racial/ethnic differences exist for the treatment of Marfan syndrome aortopathy. The 2014 Pediatric Heart Network randomised trial of losartan versus atenolol in Marfan syndrome paediatric and young adult patients showed no treatment differences in the rate of aortic root growth over 3 years; however, they did not examine racial/ethnic differences, and recent data suggest that angiotensin receptor blockers may have different pharmacologic effects in different racial/ethnic populations.
Methods:
We performed a secondary analysis of public-use data from the Pediatric Heart Network randomised trial comparing the differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic patients) amongst the treatment groups for the primary outcome of rate of aortic root enlargement by z score and secondary outcome of rate of change of absolute diameter of aortic root, z score and absolute diameter of ascending aorta, and blood pressure changes.
Results:
For aortic root enlargement by z score amongst non-Hispanic White patients, patients on losartan exhibited an annual z score change of –0.090 ± 0.016, compared to –0.146 ± 0.015 for those on atenolol (p = 0.01), favouring atenolol. For Hispanic and non-Hispanic Black patients, there was no difference in primary or secondary outcomes between treatment groups.
Conclusion:
Non-Hispanic White patients had a small, but statistically significantly greater decrease in aortic root z score favouring atenolol over losartan. There were no significant differences amongst Hispanic or non-Hispanic Black patients, which may be due to relatively small size numbers. These findings may have important implications for medication selection by race/ethnicity in Marfan syndrome patients, which has not previously been evaluated in studies.
The prevalence of attention deficit/hyperactivity disorder in the general population is common and is now diagnosed in 4%–12% of children. Children with CHD have been shown to be at increased risk for attention deficit/hyperactivity disorder. Case reports have led to concern regarding the use of attention deficit/hyperactivity disorder medications in children with underlying CHD. We hypothesised that medical therapy for patients with CHD and attention deficit/hyperactivity disorder is safe.
Methods:
A single-centre, retrospective chart review was performed evaluating for adverse events in patients aged 4–21 years with CHD who received attention deficit/hyperactivity disorder therapy over a 5-year span. Inclusion criteria were a diagnosis of CHD and concomitant medical therapy with amphetamines, methylphenidate, or atomoxetine. Patients with trivial or spontaneously resolved CHD were excluded from analysis.
Results:
In 831 patients with CHD who received stimulants with a mean age of 12.9 years, there was only one adverse cardiovascular event identified. Using sensitivity analysis, our median follow-up time was 686 days and a prevalence rate of 0.21% of adverse events. This episode consisted of increased frequency of supraventricular tachycardia in a patient who had this condition prior to initiation of medical therapy; the condition improved with discontinuation of attention deficit/hyperactivity disorder therapy.
Conclusion:
The incidence of significant adverse cardiovascular events in our population was similar to the prevalence of supraventricular tachycardia in the general population. Our single-centre experience demonstrated no increased risk in adverse events related to medical therapy for children with attention deficit/hyperactivity disorder and underlying CHD. Further population-based studies are indicated to validate these findings.
This work studies phase-separated fibers in the CaO–SiO2 and NiO–SiO2 systems. The nature of the phase-separated microstructures and underlying phase equilibria are discussed, including dimensionality, composition, and phase formation as well as the realization of ferrimagnetic behavior in the NiO–SiO2 fibers based on the formation of metallic Ni inclusions. In addition to understanding the composition/processing relationships in these systems, the work represents a step forward toward novel magneto-optic fibers. It is important to understand the underlying materials science in order to advance the properties of novel optical fibers possessing engineered heterogeneities in the core.
Alcohol and cannabis remain the substances most widely used by adolescents. Better understanding of the dynamic relationship between trajectories of substance use in relation to neuropsychological functioning is needed. The aim of this study was to examine the different impacts of within- and between-person changes in alcohol and cannabis use on neuropsychological functioning over multiple time points.
Methods:
Hierarchical linear modeling examined the effects of alcohol and cannabis use on neuropsychological functioning over the course of 14 years in a sample of 175 adolescents (aged 12–15 years at baseline).
Results:
Time-specific fluctuations in alcohol use (within-person effect) predicted worse performance across time on the Wechsler Abbreviated Scale of Intelligence Block Design subtest (B = −.05, SE = .02, p = .01). Greater mean levels of percent days of cannabis use across time (between-person effect) were associated with an increased contrast score between Delis–Kaplan Executive Function System Color Word Inhibition and Color Naming conditions (B = .52, SE = .14, p < .0001) and poorer performance over time on Block Design (B = −.08, SE = .04, p = .03). Neither alcohol and/nor cannabis use over time was associated with performance in the verbal memory and processing speed domains.
Conclusions:
Greater cumulative cannabis use over adolescence may be linked to poorer inhibitory control and visuospatial functioning performance, whereas more proximal increases in alcohol consumption during adolescence may drive alcohol-related performance decrements in visuospatial functioning. Results from this prospective study add to the growing body of literature on the impact of alcohol and cannabis use on cognition from adolescent to young adulthood.
To examine the association between level of food security and diabetes self-management among food pantry clients, which is largely not possible using clinic-based sampling methods.
Design
Cross-sectional descriptive study.
Setting
Community-based food pantries in California, Ohio and Texas, USA, from March 2012 through March 2014.
Subjects
Convenience sample of adults with diabetes queuing at pantries (n 1237; 83 % response). Sampled adults were stratified as food secure, low food secure or very low food secure. We used point-of-care glycated Hb (HbA1c) testing to determine glycaemic control and captured diabetes self-management using validated survey items.
Results
The sample was 70 % female, 55 % Latino/Hispanic, 25 % white and 10 % black/African American, with a mean age of 56 years. Eighty-four per cent were food insecure, one-half of whom had very low food security. Mean HbA1c was 8·1 % and did not vary significantly by food security status. In adjusted models, very-low-food-secure participants, compared with both low-food-secure and food-secure participants, had poorer diabetes self-efficacy, greater diabetes distress, greater medication non-adherence, higher prevalence of severe hypoglycaemic episodes, higher prevalence of depressive symptoms, more medication affordability challenges, and more food and medicine or health supply trade-offs.
Conclusions
Few studies of the health impact of food security have been able to examine very low food security. In a food pantry sample with high rates of food insecurity, we found that diabetes self-management becomes increasingly difficult as food security worsens. The efficacy of interventions to improve diabetes self-management may increase if food security is simultaneously addressed.
Law can greatly facilitate responses to public health emergencies, including naturally-occurring infectious disease outbreaks and intentional or accidental exposures to chemical, biological, radiological, or nuclear (CBRN) agents. At the federal level, the Secretary of the Department of Health and Human Services (HHS), as the lead for federal public health and medical responses to public health emergencies and incidents, has a range of authorities to support federal, state, tribal, local, and territorial responses. For example, under the Public Health Service (PHS) Act, the Secretary may provide temporary assistance to States to meet health emergency needs or deploy medicine and supplies from the Strategic National Stockpile. The Secretary also may determine that a disease or disorder presents a public health emergency, which may be the first step in triggering other critical legal authorities for response.
Since the 2001 anthrax attacks, one focus of public health preparedness has been on developing, distributing, and rapidly dispensing medical countermeasures (MCMs) for CBRN emergencies and pandemics.
We assessed characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among residents of 22 nursing homes. Of MRSA-positive swabs, 25% (208/824) were positive for CA-MRSA. Median facility CA-MRSA percentage was 22% (range, 0%–44%). In multivariate models, carriage was associated with age less than 65 years (odds ratio, 1.2; P < .001) and Hispanic ethnicity (odds ratio, 1.2; P = .006). Interventions are needed to target CA-MRSA.
The wheat stem sawfly, Cephus cinctus Norton, is a major insect pest in dryland wheat (Triticum L. spp.; Poaceae) fields in the northern Great Plains of the United States and in southern regions of the prairie provinces of Canada. Field infestations by this pest commonly show a distinct “edge effect”, with infestation levels highest at the field edge and declining inwards. In this study, we characterized the edge effect of C. cinctus infested wheat fields in Montana at four locations in two separate years. "Infestation level" refers to the average proportion of wheat stems infested with C. cinctus in samples collected in a given wheat field. The gradual decrease in C. cinctus infestation towards the centre of wheat fields is referred to as the “infestation slope”, and it was presented as a proportion of infestation level at field edges. We showed that (i) for most of the fields bordering grassland or fallow wheat, a simple exponential decline curve provided a significant fit to the infestation slope; (ii) the infestation slopes in different fields and in different directions within fields were similar and appeared to be independent of the overall infestation level; and (iii) the relationship between infestation level and the proportion of samples infested followed an asymptotic curve, which indicates a high level of dispersal of ovipositing C. cinctus females. The general perception has been that the edge effect of C. cinctus infestation is a result of ovipositing C. cinctus females being both weak flyers and short-lived, but our results do not fully corroborate this perception. Currently, the only reliable way to detect C. cinctus infestations is to dissect individual stems and look for developing instars. However, this type of sampling is extremely time consuming and labor intensive and therefore impractical for wheat growers. Increasing the understanding of the spatial patterns in C. cinctus infestations is a first step towards development of an optimal sampling plan for this important field pest. Thus, the results presented are relevant for researchers involved in sampling designs and integrated pest management procedures for field pests. We discuss behavioral and evolutionary factors that may contribute to the edge effect of C. cinctus infestations.
The morphology of all life stages of the semi-aquatic nematocerous fly, Axymyia furcata McAtee (Diptera: Axymyiidae), is documented, with emphasis on use of scanning electron microscopy (SEM). Our data on some life stages (e.g., egg, first-instar larvae) represent the first SEM examination of these stages in axymyiids. Among the unexpected results is absence of an egg burster in first instars. Most characters provided little evidence of a phylogenetic relationship with any other clade of nematocerous Diptera, reflecting a need for comprehensive morphological studies of the immatures of many families.