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Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.
This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.
Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.
Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.
Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.
Results of in situ U–Pb dating of calcite spherulites, cone-in-cone (CIC) calcite and calcite fibres from a calcareous concretion of the upper Ediacaran of Finnmark, Arctic Norway, are reported. Calcite spherulites from the innermost layers of the concretion yielded a lower intercept age of 563 ± 70 Ma, which, although imprecise, is within uncertainty of the age of sedimentation based on fossil assemblages. Non-deformed CIC calcite from the bottom part of the concretion yielded an age of 475 ± 25 Ma, which is interpreted as the age of CIC calcite formation during a period of fluid overpressure induced during burial of the sediments. Deformed CIC calcite from the top part of the concretion yielded an age of 418 ± 23 Ma, which overlaps with a known Caledonian tectono-metamorphic event, and indicates a potential post-depositional overprint at this time. Calcite fibres that grew in small fissures along spherulite rims, which are interpreted as a recrystallization feature during deformation and formation of a cleavage, gave an imprecise age of 486 ± 161 Ma. Our results show that U–Pb dating of calcite can provide age constraints for ancient carbonates and syn- to post-depositional processes that operated during burial and metamorphic overprinting.
We analyzed the δ2H composition of n-alkanes isolated from Laguna Zoncho, a small lake in southern Pacific Costa Rica, to reconstruct paleohydrology. Using a core that spans the past 3600 years, we found evidence of dry periods, most notably during the Terminal Classic Drought (TCD; ~1200 cal yr BP) and the Little Ice Age (~400 cal yr BP). Previous work at Laguna Zoncho, using bulk sedimentary δ13C and geochemical analysis, found that agriculture began to decline during the TCD. Our δ2H records confirm the occurrence of arid conditions coincident with the TCD at Laguna Zoncho and show that, despite receiving more than 3000 mm of precipitation per year, this region is susceptible to multidecadal droughts.
Children treated for brain tumors often experience social and emotional difficulties, including challenges with emotion regulation; our goal was to investigate the attention-related component processes of emotion regulation, using a novel eye-tracking measure, and to evaluate its relations with emotional functioning and white matter (WM) organization.
Fifty-four children participated in this study; 36 children treated for posterior fossa tumors, and 18 typically developing children. Participants completed two versions of an emotion regulation eye-tracking task, designed to differentiate between implicit (i.e., automatic) and explicit (i.e., voluntary) subprocesses. The Emotional Control scale from the Behavior Rating Inventory of Executive Function was used to evaluate emotional control in daily life, and WM organization was assessed with diffusion tensor imaging.
We found that emotional faces captured attention across all groups (F(1,51) = 32.18, p < .001, η2p = .39). However, unlike typically developing children, patients were unable to override the attentional capture of emotional faces when instructed to (emotional face-by-group interaction: F(2,51) = 5.58, p = .006, η2p = .18). Across all children, our eye-tracking measure of emotion regulation was modestly associated with the parent-report emotional control score (r = .29, p = .045), and in patients it was associated with WM microstructure in the body and splenium of the corpus callosum (all t > 3.03, all p < .05).
Our findings suggest that an attention-related component process of emotion regulation is disrupted in children treated for brain tumors, and that it may relate to their emotional difficulties and WM organization. This work provides a foundation for future theoretical and mechanistic investigations of emotional difficulties in brain tumor survivors.
To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.
A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.
Navajo Nation, USA.
Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles.
The Navajo Fruit and Vegetable Prescription (FVRx) Programme.
A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.
New information on acritarchs from the Duolbagáisá Formation, Digermulen Peninsula, Arctic Norway, enable recognition of the three Cambrian Series 2 acritarch-based zones: the Skiagia ornata–Fimbriaglomerella membranacea, Heliosphaeridium dissimilare–Skiagia ciliosa and Volkovia dentifera–Liepaina plana Assemblage zones. Acritarchs of the Skiagia ornata–Fimbriaglomerella membranacea Zone (Cambrian Stage 3) appear near the base of the unit, close to an undetermined trilobite. In the Upper Member of the Duolbagáisá Formation, in levels with Kjerulfia n. sp. and Elliptocephala n. sp., appears an assemblage with abundant Skiagia ciliosa, indicative of the Heliosphaeridium dissimilare–Skiagia ciliosa Zone. A few metres higher appear Liepaina plana, Heliosphaeridium notatum and Retisphaeridium dichamerum, which indicate the Volkovia dentifera–Liepaina plana Zone (Cambrian Stage 4). The transition between the Duolbagáisá Formation and the overlying Kistedalen Formation is marked by the appearance of Comasphaeridium longispinosum, Multiplicisphaeridium llynense and Eliasum llaniscum, diagnostic of the Miaolingian Series. This coincides with the disappearance of Skiagia; occurrences of Skiagia in Miaolingian strata consist of reworked material related to the Hawke Bay regression at the Cambrian Stage 4–Wuliuan transition. The absence of Skiagia in higher levels of the Duolbagáisá Formation and Kistedalen Formation suggests that no unconformity formed during the Hawke Bay regression in this area. The chronostratigraphical significance of the Skiagia ornata–Fimbriaglomerella membranacea, Heliosphaeridium dissimilare–Skiagia ciliosa and Volkovia dentifera–Liepaina plana zones is critically analysed. Correlation of the Duolbagáisá Formation with peri-Gondwanan terrains of Avalonia and Iberia is established. The Digermulen Peninsula has great potential as a reference section for establishing a Cambrian chronostratigraphy based on acritarchs.
Violence and aggression are a major concern in acute inpatient psychiatric wards. Hard outcome data on the impact of service change are scarce. This poster presents the outcomes of service changes designed to improve the acute ward environment and patient experience.
Aims and objectives
To implement changes to the delivery of acute inpatient psychiatric services and to measure the outcome of these changes in objective verifiable form.
Significant changes were introduced to an acute psychiatric inpatient service. These included introducing a dedicated inpatient psychiatrist “hospitalist”, replacing weekly ward rounds with daily multidisciplinary care and discharge planning meetings and promoting increased roles for nursing staff in decision-making and patient contact. Outcomes measured included routinely recorded incidents of violence with and without injury, use of restraint for medication and use of constant nursing observation. The control group was a similar service in the same hospital subject to the same general policies and admitting patients demographically comparable, but that did not at the time undergo the interventions implemented in the trial service. All data was recorded by staff who were unaware of this study or even that any analysis of the data would occur.
Results and conclusions
Violent incidents in the intervention ward dropped by 34% per patient (p=< 0.02) whilst increasing by 3% in the control ward; restraints decreased by 28% (p=ns) whilst increasing by 12% in the control ward; with an overall reduction in constant observation. The intervention was highly effective in reducing violent incidents.
The volume of evidence from scientific research and wider observation is greater than ever before, but much is inconsistent and scattered in fragments over increasingly diverse sources, making it hard for decision-makers to find, access and interpret all the relevant information on a particular topic, resolve seemingly contradictory results or simply identify where there is a lack of evidence. Evidence synthesis is the process of searching for and summarising a body of research on a specific topic in order to inform decisions, but is often poorly conducted and susceptible to bias. In response to these problems, more rigorous methodologies have been developed and subsequently made available to the conservation and environmental management community by the Collaboration for Environmental Evidence. We explain when and why these methods are appropriate, and how evidence can be synthesised, shared, used as a public good and benefit wider society. We discuss new developments with potential to address barriers to evidence synthesis and communication and how these practices might be mainstreamed in the process of decision-making in conservation.
Aripiprazole and quetiapine are the two most recent second generation antipsychotics available in the UK. We aimed to study patients who were prescribed aripiprazole and quetiapine in routine clinical practice, to identify and compare patients who had a good clinical response.
From a data set of 22,000 electronic patient records (from 2002 to 2007), we retrospectively identified all secondary care psychiatric patients started on aripiprazole and quetiapine for schizophrenia and other psychotic disorders. We retrospectively assigned a severity and an improvement score of Clinical Global Impression (CGI) to records, to measure the effectiveness of both drugs.
89 patients were newly prescribed aripiprazole and 132 patients prescribed quetiapine, for schizophrenia and other psychotic conditions. Patients on aripiprazole had a lower initial severity of illness, CGI (Severity) 3.9 versus 4.4, p=0.0003. After excluding treatment resistant patients, a CGI (Improvement) score 1-4 (minimally to very much improved) was achieved with aripiprazole in 69% and quetiapine in 71% of patients. There were no statistical differences in overall discontinuation rates (aripiprazole 40%, quetiapine 41.5%). There were differences in mean time to discontinuation, aripiprazole,165 days, quetiapine, 267 days (p=0.017)
This study is an independent comparison of aripiprazole and quetiapine in schizophrenia and psychoses. Both aripiprazole and quetiapine were clinically effective in the majority of patients. CGI improvement scores were similar for both drugs as were overall discontinuation rates. Patients on aripiprazole, however, discontinued earlier than those discontinuing from quetiapine.
To develop a toolkit to assess the quality of institutionalised care, in both hospital and community settings, for individuals with long-term mental illness.
The toolkit was developed by the UK research teams. Items were included to assess the six domains (Living Environment; Therapeutic Environment; Treatments and Interventions; Self-management and Autonomy; Social Policy, Citizenship and Advocacy; Clinical Governance) and three cross-cutting themes (Social Inclusion; Human Rights; Recovery-based Model) which emerged from the international literature review, Delphi exercises and cross-country care standards. Following translation and piloting in each country, the toolkit was refined and tested for reliability in 20 units in each country (a total of 200 units).
Test-retest reliability was assessed using intra-class correlations and Cohen's Kappa coefficients. Factors with low reliability or extreme response biases were dropped. Remaining items were subjected to an exploratory factor analysis to test the allocation of items to domains and cross-cutting themes and improve their internal consistency. Correlations between domains were explored to determine whether or not domains could be combined.
In the next phase of the study,the toolkit domain ratings will be analysed for associations with standardised assessments of service users' quality of life, autonomy and markers of recovery to investigate whether the toolkit can provide a proxy measurement of the institution's promotion of human rights and recovery.
Prospective longitudinal investigations are needed to identify causal processes leading to schizophrenia. However, there is presently no cost-effective way to identify children who are at risk of developing schizophrenia spectrum disorders.
The present study tested the feasibility of screening community samples to identify children, aged 9-12 years, who experience a triad of putative antecedents of schizophrenia identified in previous research, including: (1) speech and/or motor development lags/problems; (2) social, emotional, or behavioural problems; and (3) psychotic-like-experiences. 3410 children and 796 caregivers completed questionnaires.
12.3% of boys and 8.0% of girls displayed the antecedent triad. Consistent with schizophrenia incidence data, children of African-Caribbean origin presented elevated risk for the antecedent triad relative to white British children. Preliminary results from event-related potential recordings in children presenting the triad (n=14; mean age: 11 years, 4 months; mean IQ: 111) and in control children experiencing none of the antecedents (n=9; mean age: 11 years, 6 months; mean IQ: 109), indicate brain function abnormalities in triad children. The amplitude of the error-related negativity (Ne/ERN) component elicited by erroneous responses to NoGo trials in a Go/NoGo task, relative to correct responses to Go trials, was reduced in children experiencing the triad (controlling for age and IQ). Similar reduction in Ne/ERN in adults with schizophrenia is thought to indicate deficits in patients’ internal monitoring of behaviour.
Questionnaire screening of community samples of children for the putative antecedents of schizophrenia is feasible. Accuracy of identification will be established only by follow-up studies.
Dysfunctional impulsivity reflects ‘recklessness without deliberation and evaluation of consequences’ and has negative consequences whereas functional impulsivity reflects ‘rapid responding to situational demands in order to maximise one's circumstances’ and often has positive consequences (1).
To examine the functional brain basis of dysfunctional impulsivity in healthy people and in people with schizophrenia.
Thirteen healthy controls and 21 schizophrenia patients (10/21 with serious repetitive violence) underwent fMRI during a Go/ NoGo task. Dysfunctional impulsivity was indexed using the Impulsiveness subscale and functional impulsivity using the Venturesomeness subscale of the Impulsiveness-Venturesomeness-Empathy questionnaire (2).
Violent patients had elevated Impulsiveness scores relative to non-violent patients and controls. Impulsiveness did not correlate significantly with task performance in healthy controls or patients. Impulsiveness, but not Venturesomeness, scores correlated during the NoGO condition with lower activity in the anterior cingulate (AC) in controls, and lower inferior temporal and hippocampal activity in patients.
These findings accord with previously reported associations between reduced hippocampal volume and dysfunctional impulsivity in schizophrenia (3) and, combined with our earlier observations of reduced AC activation during a working memory task in violent antisocial individuals (4), suggest that the influence of dysfunctional impulsivity in antisocial and criminal behaviour is mediated via deficient (inhibitory) functions of the AC and hippocampus.
High potency cannabis has been associated with greater risk, and earlier onset of psychosis. However, its effect on brain structure, particularly white matter (WM), has never been explored.
Objectives and Aims
To elucidate the interplay between cannabis potency, pattern of use (frequency and age of first use) and CC microstructure; in patients with first-episode psychosis (FEP) and healthy controls.
56 FEP and 43 healthy controls underwent Diffusion-Tensor Imaging combined with WM mapping-tractography. CC was virtually dissected and segmented to calculate Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD) and Radial Diffusivity (RD) for each CC segment.
High potency cannabis users had higher Total CC MD and Total CC AD than both low potency users and those who never used (p=0.009 and p=0.02 respectively). Daily users also had higher Total CC MD and Total CC AD than both occasional users and those who never used (p=0.02 and p=0.01 respectively). Furthermore, daily/highpotency users had higher Total CC MD than those who never used or used weekly [F(2,57)=4.7, p=0.01]. There was no effect of diagnosis or diagnosis X potency/patterns of use interactions; neither differences between users who started before the age of 15 and those who started later were detected, in any diffusivity measures.
Frequent use of high-potency cannabis significantly affects callosal microstructure, regardless of the presence of a psychotic disorder. Given the increased availability and use of high potency preparations in Europe, raising awareness about some of their detrimental effects is an important avenue to pursue.
The impact of cannabis use on brain structure, particularly white matter (WM), is poorly understood. The CC is the largest WM structure in the brain. Abnormalities revealed in the CC may underlie functional anomalies of cannabis use. This is the largest study to explore the effect of cannabis on callosal WM connectivity among first episode psychosis (FEP) and controls.
To investigate the relationship between cannabis use and WM micro-structural integrity of the CC, in FEP and healthy controls.
We evaluated 56 FEP patients (67% current cannabis users), and 43 healthy controls (44% current cannabis users). We used Diffusion Tensor Imaging combined with a WM mapping-tractography technique to investigate the microstructural integrity of the CC.
Total CC Fractional anisotropy (FA) was lower in patients than controls (p=0.05). Cannabis-using patients had lower FA of the total CC than cannabis-using controls (p=0.04). There were no differences in FA between cannabis-using patients and those who had never used. However, cannabis-using patients had higher mean diffusivity (MD) of total CC (p= 0.02), Rostral-Body (p=0.003), Anterior Mid-Body (p=0.03) and the Splenium (p=0.06) than patients who never used cannabis. There were no differences in MD between patient users who started before the age of 16 and those who started later.
Cannabis is associated with a significant effect on callosal WM integrity only in patients with psychosis. Disturbed callosal connectivity may explain some of the abnormalities with regard to the functional and clinical outcomes in FEP cannabis users, including measures of cognitive impairment.
Clinical interviews are typically used in the assessment psychosis and related clinical symptoms. However, these measures are limited by recall bias and averaging, and thus important information is lost. Ambulatory real-time monitoring devices have the advantage of providing detailed and sensitive information about symptoms. This can provide valuable information about change and fluctuations in symptoms across time. Suicide represents a substantial problem in psychiatry, but little is known about the immediate triggers of suicidal ideation. Psychological theory suggests that the instability, in addition to the intensity, of depressed mood may be an important risk factor for the development of suicidal ideation. Mobile phone-based assessments may allow for a more accurate measure of suicidality and mood across time. In this presentation, a new smart phone software application (ClinTouch) for the assessment of psychotic and related symptoms will be described. Research investigating the feasibility, acceptability, and limitations of mobile-phone based assessment will be discussed in relation to people with psychosis. Mobile phone-based research investigating the short-term predictors of thoughts about self-injury will also be considered. The talk will finish with an outline of how mobile-based assessments could be applied in clinical settings.
Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time.
FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n = 69), 3 months (n = 29) and 12 months (n = 36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point.
Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed ‘enhancement’ followed by ‘coping with unpleasant affect’ and ‘social motive’ more highly for their cannabis use than any other reason. ‘Conformity and acceptance’ followed closely. ‘Relief of positive symptoms and side effects’ was the least endorsed motive.
Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated ‘enhancement’ most highly for their cannabis use.
The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).
We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.
The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.
Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.
The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.
Alzheimer s disease (AD) is a progressive neurodegenerative disease leading to cognitive decline and eventually death. Degradation of cortical neuroplasticity is thought to be a major catalyst of AD-related cognitive decline. Repetitive transcranial magnetic stimulation (rTMS), which uses pulsed magnetism to stimulate neurons, increases cortical plasticity and induces long-lasting neuroplastic changes. Patients have benefited from rTMS to treat AD, especially when done in conjunction with cognitive training exercises. This case report presents a 31-year-old male who tested positive for an autosomal dominant mutation implicated in early-onset AD. rTMS and cognitive training were employed to assist in the delay of early-onset AD manifestation in two cycles.
Prior to each treatment cycle, the patient completed questionnaires and interviews designed to test his cognitive functioning; his spouse was interviewed to provide a third-party assessment of his functioning. Following pre-treatment data collection, 30 daily rTMS/cognitive training sessions were completed in the first cycle and 35 daily rTMS/cognitive training sessions were completed in the second cycle. The bilateral dorsolateral prefrontal cortices each received 1,000 pulses (10 Hz, 110% SMT). Tolerability and side effect data were collected after each treatment. Immediately following rTMS, the patient played cognitive training games at our Brain Fitness Center. All pre-treatment assessments were repeated after completion of the 30 sessions in the first cycle and the 35 sessions in the second cycle for comparison of pre- to post-treatment cognitive functionality.
Pre-treatment testing indicated the patient was asymptomatic before each cycle. The patient completed 30 daily rTMS sessions in the first cycle and 35 daily rTMS sessions in the second cycle. Tolerability/side effect data showed he tolerated treatment well and experienced only minor pain. The patient also completed 30 cognitive training sessions in the first cycle and 35 cognitive training sessions in the second cycle and showed moderate improvement across all cognitive domains. Post-treatment assessments indicated no change in functioning except to note the patient s improved sleep. A third treatment cycle is scheduled to begin in February 2020.
This case report supports rTMS paired with cognitive training to be a safe and tolerable treatment for early-onset AD. However, more treatment cycles must be completed before conclusions about its efficacy can be determined.