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Psychotic disorders are central to mental health service provision and a common theme of academic research programmes in Ireland, which explore the neurobiological and psychosocial risk factors underpinning the development and progression of these illnesses. While we await the discovery of novel pharmacological treatment targets for psychotic disorders, it is important to employ our existing management strategies to optimal effect. In this special issue on psychosis, a selection of clinical research studies and reviews from Irish researchers, and often of Irish populations, are brought together which span the trajectory of psychotic illness from early intervention to treatment resistance. The topics include the characteristics and course of first episode psychosis cohorts, real-world evaluation of early intervention services, management strategies for treatment resistant schizophrenia and neurobiological research into social stress. The current editorial provides an overview of these papers and highlights the initial steps of the Irish Psychosis Research Network towards developing an integrated clinical research network focusing on the treatment and research into psychotic disorders.
Antibiotics are widely used by all specialties in the hospital setting. We evaluated previously defined high-risk antibiotic use in relation to Clostridioides difficile infections (CDIs).
We analyzed 2016–2017 data from 171 hospitals. High-risk antibiotics included second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides. A CDI case was a positive stool C. difficile toxin or molecular assay result from a patient without a positive result in the previous 8 weeks. Hospital-associated (HA) CDI cases included specimens collected >3 calendar days after admission or ≤3 calendar days from a patient with a prior same-hospital discharge within 28 days. We used the multivariable Poisson regression model to estimate the relative risk (RR) of high-risk antibiotic use on HA CDI, controlling for confounders.
The median days of therapy for high-risk antibiotic use was 241.2 (interquartile range [IQR], 192.6–295.2) per 1,000 days present; the overall HA CDI rate was 33 (IQR, 24–43) per 10,000 admissions. The overall correlation of high-risk antibiotic use and HA CDI was 0.22 (P = .003), and higher correlation was observed in teaching hospitals (0.38; P = .002). For every 100-day (per 1,000 days present) increase in high-risk antibiotic therapy, there was a 12% increase in HA CDI (RR, 1.12; 95% CI, 1.04–1.21; P = .002) after adjusting for confounders.
High-risk antibiotic use is an independent predictor of HA CDI. This assessment of poststewardship implementation in the United States highlights the importance of tracking trends of antimicrobial use over time as it relates to CDI.
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.
Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7–9.0) for season 2011/2012, 36.7 (95% UI: 31.2–42.8) for 2012/2013, 9.1 (95% UI: 6.3–12.9) for 2013/2014, 41.1 (95% UI: 35.0–47.7) for 2014/2015, 39.4 (95% UI: 33.4–46.1) for 2015/2016 and 27.8 (95% UI: 22.7–33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation – with appropriately quantified uncertainty – of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.
To examine similarities and differences in the demographic and clinical profiles of young people (15–25 years of age) referred between the mental health services (MHS) and Jigsaw Galway.
A retrospective chart review was conducted of clinical files of individuals attending secondary MHS who had been referred to or from Jigsaw Galway over a 5-year period. Differences in demographic and clinical data between individuals referred to or from Jigsaw Galway were compared.
A recent act of self-harm was more prevalent in individuals referred from Jigsaw to the adult MHS (p=0.02). No other demographic or clinical differences were detected between individuals attending Jigsaw Galway and the MHS.
Education sessions for clinical staff working in primary care, Jigsaw Galway and the MHS are suggested to support clinicians in choosing the best referral pathway, which may more optimally address young people’s mental health difficulties.
To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission in the LTCF and in the hospital during acute-care admissions.
A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS).
Veterans Affairs hospital and affiliated LTCF.
The study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases.
Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases.
Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.
Introduction: Health advocacy training is an important part of emergency medicine practice and education. There is little agreement, however, about how advocacy should be taught and evaluated in the postgraduate context, and there is no consolidated evidence-base to guide the design and implementation of post-graduate health advocacy curricula. This literature review aims to identify existing models used for teaching and evaluating advocacy training, and to integrate these findings with current best-practices in medical education to develop practical, generalizable recommendations for those involved in the design of postgraduate advocacy training programs. Methods: Ovid MEDLINE and PubMed searches combined both MeSH and non-MeSH variations on advocacy and internship and residency. Forward snowballing that incorporated grey literature searches from accreditation agencies, residency websites and reports were included. Articles were excluded if unrelated to advocacy and postgraduate medical education. Results: 507 articles were identified in the search. A total of 108 peer reviewed articles and 38 grey literature resources were included in the final analysis. Results show that many regulatory bodies and residency programs integrate advocacy training into their mission statements and curricula, but they are not prescriptive about training methods or assessment strategies. Barriers to advocacy training were identified, most notably confusion about the definition of the advocate role and a lower value placed on advocacy by trainees and educators. Common training methods included didactic modules, standardized patient encounters, and clinical exposure to vulnerable populations. Longitudinal exposure was less common but appeared the most promising, often linked to scholarly or policy objectives. Conclusion: This review indicates that postgraduate medical education advocacy curricula are largely designed in an ad-hoc fashion with little consistency across programs even within a given discipline. Longitudinal curriculum design appears to engage residents and allows for achievement of stated outcomes. Residency program directors from emergency medicine and other specialties may benefit from promising models in pediatrics, and a shared portal with access to advocacy curricula and the opportunity to exchange ideas related to curriculum design and implementation.
To describe similarities and differences in mental health legislation between five jurisdictions: the Republic of Ireland, England and Wales, Scotland, Ontario (Canada), and Victoria (Australia).
An in-depth examination was undertaken focussing on the process of involuntary admission, review of Admission Orders and the legal processes in relation to treatment in the absence of patient consent in each of the five jurisdictions of interest.
All jurisdictions permit the detention of a patient if they have a mental disorder although the definition of mental disorder varies between jurisdictions. Several additional differences exist between the five jurisdictions, including the duration of admission prior to independent review of involuntary detention and the role of supported decision making.
Across the five jurisdictions examined, largely similar procedures for admission, detention and treatment of involuntary patients are employed, reflecting adherence with international standards and incorporation of human rights-based principles. Differences exist in relation to the criteria to define mental disorder, the occurrence of automatic review hearings in a timely fashion after a patient is involuntarily admitted and the role for supported decision making under mental health legislation.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis.
Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3–6 months post-treatment.
Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3–6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition.
CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
The search for extraterrestrial habitable planets will require long observation times and the intelligent selection of appropriate parent stars and target biosignatures. While life can certainly develop in the absence of photosynthesis, such life forms on earth exhibit metabolic rates several orders of magnitude less than the activity accompanying a photosynthetic-driven ecosystem. The most accessible spectral biosignatures are those accompanying a system driven away from thermodynamic equilibrium by photosynthetic activity. For example, the co-existence in a planetary atmosphere of significant amounts of ozone, oxygen, and methane would be a strong indication of biotic activity. Investigating the issue of the Habitable Zone from the standpoint of the constraints inherent in photosynthesis it appears that the absorption characteristics of photosynthetic microorganisms on this planet make it likely that photosynthetic activity can exist on planets orbiting stars to red-ward of the Sun on the H-R diagram. Such a possibility is encouraging for terrestrial planet finder efforts since stars classified red-ward of our sun (G3 to K7) account for more than 55% of our nearest neighbors.
Prediction of future changes in dynamics of the Earth’s ice sheets, mass loss and resultant contribution to sea-level rise are the main objectives of ice-sheet modeling. Mass transfer from ice sheet to ocean is, in large part, through outlet glaciers. Subglacial topography plays an important role in ice dynamics; however, trough systems have not been included in bed digital elevation models (DEMS) used in modeling, because their size is close to the model resolution. Using recently collected CReSIS MCoRDs data of subglacial topography and an algorithm that allows topographically and morphologically correct integration of troughs and trough systems at any modeling scale (5 km resolution for SeaRISE), an improved Greenland bed DEM was developed that includes Jakobshavn Isbræ, Helheim, Kangerdlussuaq and Petermann glaciers (JakHelKanPet DEM). Contrasting the different responses of two Greenland ice-sheet models (UMISM and SICOPOLIS) to the more accurately represented bed shows significant differences in modeled surface velocity, basal water production and ice thickness. Consequently, modeled ice volumes for the Greenland ice sheet are significantly smaller using the JakHelKanPet DEM, and volume losses larger. More generally, the study demonstrates the role of spatial modeling of data specifically as input for dynamic ice-sheet models in assessments of future sea-level rise.
OBJECTIVES/SPECIFIC AIMS: Recent evidence from resting-state fMRI studies have shown that brain network connectivity is altered in patients with neurodegenerative disorders. However, few studies have examined the complete connectivity patterns of these well-reported RSNs using a whole brain approach and how they compare between dementias. Here, we used advanced connectomic approaches to examine the connectivity of RSNs in Alzheimer disease (AD), Frontotemporal dementia (FTD), and age-matched control participants. METHODS/STUDY POPULATION: In total, 44 participants [27 controls (66.4±7.6 years), 13 AD (68.5.63±13.9 years), 4 FTD (59.575±12.2 years)] from an ongoing study at Indiana University School of Medicine were used. Resting-state fMRI data was processed using an in-house pipeline modeled after Power et al. (2014). Images were parcellated into 278 regions of interest (ROI) based on Shen et al. (2013). Connectivity between each ROI pair was described by Pearson correlation coefficient. Brain regions were grouped into 7 canonical RSNs as described by Yeo et al. (2015). Pearson correlation values were then averaged across pairs of ROIs in each network and averaged across individuals in each group. These values were used to determine relative expression of FC in each RSN (intranetwork) and create RSN profiles for each group. RESULTS/ANTICIPATED RESULTS: Our findings support previous literature which shows that limbic networks are disrupted in FTLD participants compared with AD and age-matched controls. In addition, interactions between different RSNs was also examined and a significant difference between controls and AD subjects was found between FP and DMN RSNs. Similarly, previous literature has reported a disruption between executive (frontoparietal) network and default mode network in AD compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Our approach allows us to create profiles that could help compare intranetwork FC in different neurodegenerative diseases. Future work with expanded samples will help us to draw more substantial conclusions regarding differences, if any, in the connectivity patterns between RSNs in various neurodegenerative diseases.
The Bering Glacier–Bagley Icefield system in Alaska is currently surging (2011). Large-scale elevation changes and small-scale elevation-change characteristics are investigated to understand surge progression, especially mass transport from the pre-surge reservoir area to the receiving area and propagation of the kinematic surge wave as manifested in heavy crevassing characteristic of rapid, brittle deformation. This analysis is based on airborne laser altimeter data collected over Bering Glacier in September 2011. Results include the following: (1) Maximal crevasse depth is 60 m, reached in a rift that separates two deformation domains, indicative of two different flow regimes. Otherwise surge crevasse depth reaches 20–30 m. (2) Characteristic parameters of structural provinces are derived by application of geostatistical classification. Parameters include significance and spacing of crevasses, surface roughness and crevasse-edge curvature (indicative of crevasse age). A classification based on these parameters serves to objectively discriminate structural provinces, indicative of surge progression down-glacier and up-glacier. (3) Elevation changes from 2011 and 2010 altimetry show 40–70 m surface lowering in the reservoir area in lower central Bering Glacier and 20–40m thickening near the front in Tashalich arm. Combining elevation changes with results of crevasse profilometry and pattern analysis, the rapid progression of the surge can be mathematically–physically reconstructed.
The dynamics of a surge is manifested in the crevasse patterns: literally, deformation state frozen in ice. This basic observation is utilized as the concept of an automated approach to map and analyze deformation stages and progression of surge kinematics. The classification method allows imagery to be used as geophysical data and is applied to aerial observations (photographic and video imagery, GPS data) collected in September 2011 during the surge of the Bering Glacier–Bagley Ice Valley system, Alaska, USA. As the third dimension that complements two-dimensional imagery, ice-surface elevation is observed using aerial laser altimetry. The classification method builds on concepts from signal processing, geostatistical data analysis and neural networks. Steps include calculation of generalized directional vario functions from image data and composition into feature vectors. The vario function operates as an information filter that retains spatial characteristics at an intermediate scale that captures crevasse spacing, anisotropy and other generalized roughness properties. Association of feature vectors to crevasse classes and hence deformation types employs a connectionist algorithm. In general, the connectionist–geostatistical classification allows the mapping of kinematic changes in crevassed glaciers.
Dynamic ice-sheet models are used to assess the contribution of mass loss from the Greenland ice sheet to sea-level rise. Mass transfer from ice sheet to ocean is in a large part through outlet glaciers. Bed topography plays an important role in ice dynamics, since the acceleration from the slow-moving inland ice to an ice stream is in many cases caused by the existence of a subglacial trough or trough system. Problems are that most subglacial troughs are features of a scale not resolved in most ice-sheet models and that radar measurements of subglacial topography do not always reach the bottoms of narrow troughs. The trough-system algorithm introduced here employs mathematical morphology and algebraic topology to correctly represent subscale features in a topographic generalization, so the effects of troughs on ice flow are retained in ice-dynamic models. The algorithm is applied to derive a spatial elevation model of Greenland subglacial topography, integrating recently collected radar measurements (CReSIS data) of the Jakobshavn Isbræ, Helheim, Kangerdlussuaq and Petermann glacier regions. The resultant JakHelKanPet digital elevation model has been applied in dynamic ice-sheet modeling and sea-level-rise assessment.
Clozapine is an atypical antipsychotic agent used primarily in the management of treatment-resistant schizophrenia. Previous studies have demonstrated clozapine’s superior efficacy over other antipsychotic medications in treating this population of patients. The aim of this study was to assess if the number of hospital admissions and days spent in hospital reduced with the initiation of clozapine, compared with when the same sample of patients were prescribed other antipsychotics prior to clozapine initiation.
A mirror-image study design was adopted. In this case the intervention under study was the initiation of clozapine. Information was collected retrospectively from the charts of patients attending the University Hospital Galway clozapine clinic. The number of admissions and number of hospital days were collected for each patient over the 3 years before and after clozapine initiation. Wilcoxon’s signed-rank test was used to test for statistical significance.
The total sample size comprised of 62 patients, of which the majority were male (74.2%) and had a diagnosis of schizophrenia (82.3%). The mean dose of clozapine was 417 mg, and mean age of the sample was 38 years. Mean number of hospital admissions reduced from 2.8 to 0.8 (p<0.0001) following initiation of clozapine. Mean number of days spent in hospital reduced from 116.4 to 17.1 (p<0.0001).
After initiation of clozapine treatment, patients experience a substantial reduction in number of hospital admissions and number of days spent in hospital when compared with a similar period prior to clozapine initiation.