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ABSTRACT IMPACT: This work will inform the ongoing development of adaptive capacity and preparedness of the CTSA Program and other clinical and translational research organizations in their quest of improving processes that drive outcomes and impacts, shaping effective programs and services, and strengthening their emergency readiness and sustainability. OBJECTIVES/GOALS: -Share the progress and preliminary findings of an ‘Adaptive Capacity and Preparedness of CTSA Hubs’ CTSA Working Group; -Improve our awareness and understanding of the efficient and effective changes helping CTSA hubs build robust capacity to address METHODS/STUDY POPULATION: A multi-case study including: - Triangulating multiple sources of information and mixed methods (survey/interviews of research administrators, researchers, evaluators, and other key stakeholders), literature review, document and M&E system information analysis, and expert review; - Describing CTSA hubs’ experiences as related to research implementation, translation, and support during the time of emergency; - Administering a comprehensive survey of the CTSAs addressing their challenges, lessons learned, and practices that work in various program components/areas. Data collection includes aggregate and cross-sectional data, with representation based on CTSA size, maturity, and population density. RESULTS/ANTICIPATED RESULTS: The described approach shows sound promise to investigate and share strategies and best practices for building adaptive capacity and preparedness of CTSAs -- across various scientific sectors, translational research spectrum, and the goals outlined by NCATS for the CTSA program. The anticipated results of this research will include the identified/shared innovative solutions and lessons learned for this rapidly emerging, high-priority clinical and translational science issue. ‘High-quality lessons learned’ are those that represent principles extrapolated from multiple sources and triangulated to increase transferability to new contexts and situations. DISCUSSION/SIGNIFICANCE OF FINDINGS: The project provides useful knowledge and tools to research organizations and stakeholders across multiple disciplines -- for mitigating the impact of the COVID-19 disaster via effective adjusting programs, practices, and processes, and building capacity for future successful, ‘emergency ready and responsive’ research and training.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:
1. determine the extent to which this is altered in schizophrenia and
2. use a verbal fluency paradigm.
This is relevant since:
1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and
2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.
Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.
The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.
Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.
The heritability of the brain’s structure and function in schizophrenia remains elusive
To assess the influence of genetic and environmental factors on executive function in schizophrenia.
A twin-sibling study of 206 subjects; 163 twins, varying in their zygosity and concordance for schizophrenia, and 43 singletons from sibling clusters varying in their concordance for schizophrenia. We assessed performance and regional brain activation using functional magnetic resonance imaging, during a phonological verbal fluency task.
Patients and their unaffected relatives developed greater activation in the left inferior frontal gyrus, and greater deactivation in the middle temporal gyri bilaterally. These features were maximally evident in subjects with schizophrenia. When the analysis was restricted to the unaffected relatives and healthy controls, a similar pattern was evident. Heritability was greatest in the left hippocampus and the right middle temporal gyrus. Genetic modelling indicated a phenotypic correlation between schizophrenia and increased activity in the inferior frontal gyrus and reduced activity in the left middle temporal gyrus and left hippocampus, which appeared principally due to shared genetic effects.
Both schizophrenia and its familial vulnerability were associated with altered frontal, parahippocampal and temporal activation during verbal fluency. The altered left inferior frontal activity was particularly associated with schizophrenia, while altered left medial temporal and right middle temporal activity were more heritable. The latter was more intimately linked to the genetic risk for schizophrenia, and thus the better candidate intermediate phenotype.
To evaluate the initial (3 months) all-cause discontinuation and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, stratified by previous treatment.
These two studies (NCT00705783 & NCT00706654) were double-blind, placebo- or active-controlled assessing the efficacy and safety of AOM-400mg. Detailed study designs have been reported previously (1, 2). This analysis was conducted on the pooled population in the first 3 months after initiating AOM-400mg treatment, on patients who received at least one dose of AOM-400mg. Outcome measures are reported for groups stratified by prior treatment.
During the first 3 months of treatment, discontinuation due to all-causes (except for those who discontinued due to the sponsor stopping the NCT00705783 study early after pre-specified efficacy parameters were met) as well as due to adverse events are presented in Table 1. The rates of insomnia and akathisia are shown in Table 1
Aripiprazole once-monthly 400mg appeared equally safe and effective (as measured by all cause discontinuation) in the first 3 months after initiation, regardless of treatment prior to entering trials.
Antipsychotic other than oral aripiprazole (converted) n=581
Perfectionism is a transdiagnostic risk factor across psychopathology. The Clinical Perfectionism Questionnaire (CPQ) was developed to assess change in order to provide clinical utility, but currently the psychometric properties of the CPQ with adolescents is unknown.
To assess the factor structure and construct validity of the CPQ in female adolescents.
The CPQ was administered to 267 females aged 14–19 years of age. Confirmatory factor analysis (CFA) was used to examine the validity of the two-factor model and a second-order factor model. Pearson correlations were used to evaluate the relationships between the CPQ and a wide range of measures of perfectionism, psychopathology and personality traits.
The study demonstrated internal consistency, construct validity and incremental validity of the CPQ in a sample of female adolescents. The CFA in the present study confirmed the two-factor model of the CPQ with Factor 1 relating to perfectionistic strivings and Factor 2 representing perfectionistic concerns. The second-order two factor model indicated no deterioration in fit.
The two-factor model of the CPQ fits with the theoretical definition of clinical perfectionism where the over-dependence of self-worth on achievement and concern over mistakes are key elements. The CPQ is suitable for use with female adolescents in future research that seeks to better understand the role of perfectionism in the range of mental illnesses that impact youth.
Background: Mindfulness-based cognitive therapy (MBCT) has evidence of efficacy in a range of populations, but few studies to date have reported on MBCT for treatment of anxious and depressive symptoms in Parkinson's disease (PD). Aims: The aim of this study was to examine the efficacy of modified MBCT in reducing symptoms of anxiety and depression and improving quality of life in PD. Method: Thirty-six individuals with PD were randomly assigned to either modified MBCT or a waitlist control. Changes in symptoms of anxiety, depression and quality of life were compared at group level using generalized linear mixed models and at individual level using reliable change analysis. Results: At post-treatment, there was a significant reduction in depressive symptoms for people undertaking modified MBCT at both group and individual levels compared with controls. There was no significant effect on anxiety or quality of life at the group level, although significantly more people had reliable improvement in anxiety after modified MBCT than after waitlist. Significantly more waitlist participants had reliable deterioration in symptoms of anxiety and depression than those completing modified MBCT. Most participants stayed engaged in modified MBCT, with only three drop-outs. Discussion: This proof-of-concept study demonstrates the potential efficacy of modified MBCT as a treatment for depressive symptoms in Parkinson's disease and suggests further research is warranted.
Despite increasing evidence for the benefits of psychological treatments (PTs) in low- and middle-income countries, few national health systems have adopted PTs as standard care. We aimed to evaluate the effectiveness of a group interpersonal psychotherapy (IPT-G) intervention, when delivered by lay community health workers (LCHWs) in a low-resource government health system in Uganda. The intended outcome was reduction of depression among caregivers of children with nodding syndrome, a neuropsychiatric condition with high morbidity, mortality and social stigma.
A non-randomized trial design was used. Caregivers in six villages (n = 69) received treatment as usual (TAU), according to government guidelines. Caregivers in seven villages (n = 73) received TAU as well as 12 sessions of IPT-G delivered by LCHWs. Primary outcomes were caregiver and child depression assessed at 1 and 6 months post-intervention.
Caregivers who received IPT-G had a significantly greater reduction in the risk of depression from baseline to 1 month [risk ratio (RR) 0.25, 95% confidence interval (CI) 0.10–0.62] and 6 months (RR 0.33, 95% CI 0.11–0.95) post-intervention compared with caregivers who received TAU. Children of caregivers who received IPT-G had significantly greater reduction in depression scores than children of TAU caregivers at 1 month (Cohen's d = 0.57, p = 0.01) and 6 months (Cohen's d = 0.54, p = 0.03). Significant effects were also observed for psychological distress, stigma and social support among caregivers.
IPT-G delivered within a low-resource health system is an effective PT for common mental health problems in caregivers of children with a severe neuropsychiatric condition and has psychological benefits for the children as well. This supports national health policy initiatives to integrate PTs into primary health care services in Uganda.
Background: The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. Aims: We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. Method: The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. Results: OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. Conclusion: This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.
Background: Perfectionism is strongly associated with obsessive compulsive disorder (OCD). Cognitive behavioural therapy for perfectionism (CBT-P) has been found to result in reductions in a range of symptoms in individuals with anxiety disorders, depression and eating disorders. Aim: To pilot-test the efficacy of group CBT for perfectionism in participants with OCD and elevated perfectionism. Method: Participants were randomized to receive immediate 8-week group CBT-P (n = 4) or an 8-week waitlist followed by CBT-P (n = 7). Results: Reliable reductions and a large effect size indicated that CBT-P was associated with improvements in perfectionism and OCD severity at post-test. However, these changes were not clinically significant and drop-out was high, resulting in a small final sample. Conclusions: CBT-P may be effective in reducing perfectionism and disorder-specific OCD symptoms. However, the high drop-out rate and lack of clinically significant findings suggest that further research needs to be conducted to determine the efficacy of CBT for perfectionism in OCD.
Perfectionism is a risk and maintaining factor across psychopathology and has been proposed to be a transdiagnostic process. The aim of this study was to examine the reliability and validity of the Clinical Perfectionism Questionnaire (CPQ) in 32 adults (75% female, M age = 35.54 years, SD = 9.71) with a range of psychological disorders, presenting for treatment of clinical perfectionism. There was evidence that the CPQ was correlated with established measures of perfectionism and theoretically related constructs including self-criticism and dichotomous thinking. The CPQ was also able to predict treatment outcome. The internal consistency was not adequate in the current study; however, the sample size was small. Future studies should examine the psychometric properties of the CPQ in a larger sample of individuals with a range of psychological disorders.
Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear.
We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges’ g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects.
A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = −1.00, 95% CI −1.28 to −0.73, p < 0.001), and loosing superiority by days 10–12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5–8 (Hedges' g = −0.37, 95% CI −0.66 to −0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3–5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3–5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant.
A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance.
Growth of GaN on Si(111) and Ge coated Si(111) using pulsed electron beam deposition (PED) process is reported. GaN was deposited on Si(111) and Ge/Si(111) at 600°C in an N2 environment without any surface pre-treatment such as pre-nitridation. X-ray diffraction confirmed that c-plane oriented GaN was grown. Photoluminescence showed near-band-edge emission, the intensity of which was improved with hydrogen passivation. Electrical characterization showed n-type conductivity with room temperature electron mobilities in the range of 300 cm2/V-sec.
Background: To date no research has investigated the link between Post Traumatic Stress Disorder (PTSD) and perfectionism in a clinical sample. Aims: The aim of the current study was to examine whether there is a relationship between PTSD and perfectionism. This is important to address as many studies have demonstrated a link between other anxiety disorders, eating disorders, depression and perfectionism. The research also aimed to examine whether rumination was a mediator of the relationship between PTSD and perfectionism. Method: The sample consisted of 30 participants who were currently in treatment for PTSD. Results: The results suggest that perfectionism and PTSD symptoms were significantly correlated. In addition, rumination was a significant mediator of the relationship between Concern over Mistakes and PTSD. Conclusions: These findings help increase understanding about the relationships of perfectionism and rumination in PTSD and have implications for the treatment of PTSD.
To determine (1) the accuracy of positron emission tomography – computed tomography in the diagnosis of head and neck cancer, (2) the learning curve involved, and (3) whether its use alters patient management.
Materials and methods:
A retrospective study including 80 patients with head and neck cancer who underwent positron emission tomography – computed tomography image fusion at Blackpool Victoria Hospital.
Fifty-three patients underwent positron emission tomography – computed tomography for staging (32 for detection of a primary tumour and 21 for detection of distant metastasis) and 27 for detection of loco-regional recurrence. Ten primary tumours and 20 recurrences were accurately diagnosed by this method. Eighteen patients had their tumour stage and management modified as a result of this method of imaging. The effect of the learning curve resulted in better true positive detection rates, one year after introduction (81 versus 61 per cent). The sensitivity and specificity of this method in detecting head and neck cancer were 70 and 42 per cent, respectively, whereas those of conventional imaging were 73 and 51 per cent, respectively.
Compared with magnetic resonance imaging, the benefits of positron emission tomography – computed tomography may be limited to diagnosis of recurrence, as it is less hindered by tissue fibrosis, radiotherapy-related oedema, scarring and inflammation.
Using 16 non-clinical adults from the community, this study examined the effects on well-being of a group intervention consisting of a 4-week behavioural activation component followed by a 3-week mindfulness component, finishing with an integrating closure session. Results from intention-to-treat analyses showed moderate and significant improvements in psychological distress and several indices of well-being after the behavioural activation component. These improvements continued through the mindfulness component of the intervention such that effects were greater after participants had received the complete intervention. Half of the participants reported reliable and clinically significant improvement in the amount of time they felt happy after the intervention and a quarter of participants reported improvement at follow-up. Behavioural activation and mindfulness interventions may provide a useful framework for further research with non-clinical populations who wish to enhance their well-being and learn skills that may protect them against depression and other mental health problems.