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Clinical intuition suggests that personality disorders hinder the treatment of depression, but research findings are mixed. One reason for this might be the way in which current assessment measures conflate general aspects of personality disorders, such as overall severity, with specific aspects, such as stylistic tendencies. The goal of this study was to clarify the unique contributions of the general and specific aspects of personality disorders to depression outcomes.
Methods
Patients admitted to the Menninger Clinic, Houston, between 2012 and 2015 (N = 2352) were followed over a 6–8-week course of multimodal inpatient treatment. Personality disorder symptoms were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition Axis II Personality Screening Questionnaire at admission, and depression severity was assessed using the Patient Health Questionnaire-9 every fortnight. General and specific personality disorder factors estimated with a confirmatory bifactor model were used to predict latent growth curves of depression scores in a structural equation model.
Results
The general factor predicted higher initial depression scores but not different rates of change. By contrast, the specific borderline factor predicted slower rates of decline in depression scores, while the specific antisocial factor predicted a U shaped pattern of change.
Conclusions
Personality disorder symptoms are best represented by a general factor that reflects overall personality disorder severity, and specific factors that reflect unique personality styles. The general factor predicts overall depression severity while specific factors predict poorer prognosis which may be masked in prior studies that do not separate the two.
Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
Aims
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Method
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
Results
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Conclusions
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs).
Methods:
SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations.
Results:
Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures.
Conclusions:
The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.
Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future ‘multi-omic’ analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other ‘omic’ factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.
In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0–38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage.
Research suggests that the way in which cognitive therapy is delivered is an important factor in determining outcomes. We test the hypotheses in which the development of a shared problem list, use of case formulation, homework tasks and active intervention strategies will act as process variables.
Method
Presence of these components during therapy is taken from therapist notes. The direct and indirect effect of the intervention is estimated by an instrumental variable analysis.
Results
A significant decrease in the symptom score for case formulation (coefficient =–23, 95% CI –44 to –1.7, P = 0.036) and homework (coefficient =–0.26, 95% CI –0.51 to –0.001, P = 0.049) is found. Improvement with the inclusion of active change strategies is of borderline significance (coefficient =–0.23, 95% CI –0.47 to 0.005, P = 0.056).
Conclusions
There is a greater treatment effect if formulation and homework are involved in therapy. However, high correlation between components means that these may be indicators of overall treatment fidelity.
Paranoia is one of the commonest symptoms of psychosis but has rarely been studied in a population at risk of developing psychosis. Based on existing theoretical models, including the proposed distinction between ‘poor me’ and ‘bad me’ paranoia, we aimed to test specific predictions about associations between negative cognition, metacognitive beliefs and negative emotions and paranoid ideation and the belief that persecution is deserved (deservedness).
Method
We used data from 117 participants from the Early Detection and Intervention Evaluation for people at risk of psychosis (EDIE-2) trial of cognitive–behaviour therapy, comparing them with samples of psychiatric in-patients and healthy students from a previous study. Multi-level modelling was utilized to examine predictors of both paranoia and deservedness, with post-hoc planned comparisons conducted to test whether person-level predictor variables were associated differentially with paranoia or with deservedness.
Results
Our sample of at-risk mental state participants was not as paranoid, but reported higher levels of ‘bad-me’ deservedness, compared with psychiatric in-patients. We found several predictors of paranoia and deservedness. Negative beliefs about self were related to deservedness but not paranoia, whereas negative beliefs about others were positively related to paranoia but negatively with deservedness. Both depression and negative metacognitive beliefs about paranoid thinking were specifically related to paranoia but not deservedness.
Conclusions
This study provides evidence for the role of negative cognition, metacognition and negative affect in the development of paranoid beliefs, which has implications for psychological interventions and our understanding of psychosis.
For people with psychosis, contact with informal caregivers is an important source of social support, associated with recovery, and with better outcomes following individual cognitive therapy (CBTp). In this study, we tested whether increased flexibility in delusional thinking, an established predictor of positive outcome following CBTp, was a possible mechanism underlying this effect.
Methods.
219 participants with delusions (mean age 38 years; 71% male; 75% White) were grouped according to the presence of a caregiver (37% with a caregiver) and caregiver level of expressed emotion (High/Low EE, 64% Low). Delusional belief flexibility was compared between groups, controlling for interpersonal functioning, severity of psychotic symptoms, and other hypothesised outcome predictors.
Results.
Participants with caregivers were nearly three times more likely than those without to show flexibility (OR = 2.7, 95% CI 1.5 to 5.0, p = 0.001), and five times more likely if the caregiving relationship was Low EE (OR = 5.0, 95% CI 2.0–13.0, p = 0.001). ORs remained consistent irrespective of controlling for interpersonal functioning and other predictors of outcome.
Conclusions.
This is the first evidence that having supportive caregiving relationships is associated with a specific cognitive attribute in people with psychosis, suggesting a potential cognitive mechanism by which outcomes following CBTp, and perhaps more generally, are improved by social support.
Background: Research suggests that core schemas are important in both the development and maintenance of psychosis. Aims: The aim of the study was to investigate and compare core schemas in four groups along the continuum of psychosis and examine the relationships between schemas and positive psychotic symptomatology. Method: A measure of core schemas was distributed to 20 individuals experiencing first-episode psychosis (FEP), 113 individuals with “at risk mental states” (ARMS), 28 participants forming a help-seeking clinical group (HSC), and 30 non-help-seeking individuals who endorse some psychotic-like experiences (NH). Results: The clinical groups scored significantly higher than the NH group for negative beliefs about self and about others. No significant effects of group on positive beliefs about others were found. For positive beliefs about the self, the NH group scored significantly higher than the clinical groups. Furthermore, negative beliefs about self and others were related to positive psychotic symptomatology and to distress related to those experiences. Conclusions: Negative evaluations of the self and others appear to be characteristic of the appraisals of people seeking help for psychosis and psychosis-like experiences. The results support the literature that suggests that self-esteem should be a target for intervention. Future research would benefit from including comparison groups of people experiencing chronic psychosis and people who do not have any psychotic-like experiences.
Internalised stigma in young people meeting criteria for at-risk mental states (ARMS) has been highlighted as an important issue, and it has been suggested that provision of cognitive therapy may increase such stigma.
Aims
To investigate the effects of cognitive therapy on internalised stigma using a secondary analysis of data from the EDIE-2 trial.
Method
Participants meeting criteria for ARMS were recruited as part of a multisite randomised controlled trial of cognitive therapy for prevention and amelioration of psychosis. Participants were assessed at baseline and at 6, 12, 18 and 24 months using measures of psychotic experiences, symptoms and internalised stigma.
Results
Negative appraisals of experiences were significantly reduced in the group assigned to cognitive therapy (estimated difference at 12 months was −1.36 (95% Cl −2.69 to −0.02), P = 0.047). There was no difference in social acceptability of experiences (estimated difference at 12 months was 0.46, 95% Cl −0.05 to 0.98, P = 0.079).
Conclusions
These findings suggest that, rather than increasing internalised stigma, cognitive therapy decreases negative appraisals of unusual experiences in young people at risk of psychosis; as such, it is a non-stigmatising intervention for this population.
Interventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed.
Aims
To document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway.
Method
Data for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed.
Results
A third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP.
Conclusions
Community education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.
Intrauterine factors important for cognitive development, such as birth weight, chorionicity and umbilical cord characteristics were investigated. A total of 663 twin pairs completed the Wechsler Intelligence Scale for Children-Revised and scores were available for Performance, Verbal and Total Intelligence Quotient (IQ). The intrauterine factors examined were birth weight, placental weight and morphology, cord knots, cord length and cord insertion. IQ scores for the varying levels of the intrauterine markers adjusting for gender and gestational age were calculated. The heritability of IQ and the association between IQ and intrauterine environment were examined. Twins with lower birth weight and cord knots had lower IQ scores. The aetiology of IQ is largely distinct from that of birth weight and cord knots, and non-shared environment may influence the observed relationships.
There is evidence that patients with schizophrenia benefit from standard cognitive behaviour therapy (CBT) only if active techniques are used (‘full therapy’). By contrast, attending sessions but not proceeding beyond engagement and assessment strategies (‘partial therapy’), or simply not attending sessions (‘no therapy’), is not associated with better outcomes. The factors leading to full therapy are unknown. We hypothesized that patients' initial ideas about the nature and extent of their problems would predict use of CBT. A match between patients' views of their problems and the principles underlying treatment would lead to better outcomes.
Method
Ninety-two patients with a recent relapse of psychosis completed the Illness Perception Questionnaire (IPQ) before receiving CBT. We examined whether their illness perceptions predicted the take-up of therapy.
Results
Patients who did not attend sessions believed their problems would not last as long as those who attended them. Those who attended sessions but did not proceed to full therapy had a lower sense of control over their problems and a more biological view of their causes. Patients who took up full therapy were more likely to attribute the cause of their problems to their personality and state of mind. The take-up of therapy was predicted neither by levels of psychiatric symptoms nor by insight.
Conclusions
People with psychosis who have psychologically orientated views of their problems, including the potential to gain control over them, may be more likely to engage fully and do well with standard CBT for psychosis, irrespective of the severity of their problems.
Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology.
Method
The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization.
Results
Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective.
Conclusions
Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.
To ascertain how new funding arrangements, introduced in New Zealand's 2001 Primary Health Care (PHC) Strategy, have impacted on the expansion of nurses’ role in general practice.
Background
Nurses are central to the new policy that was designed to improve the health status of New Zealanders and reduce inequalities in health. Nurses were to be a crucial part of the PHC team, expanding their current roles to provide increased access to appropriate services. This paper investigates how the new funding arrangements, introduced as part of the policy, have impacted on the expansion of nurses’ roles and consequently the realisation of the policy goals.
Methods
Semi-structured interviews were undertaken with 128 key stakeholders five years after the introduction of the PHC Strategy, and surveys were completed by practice nurses, general practitioners and practice managers in purposively selected practices within the 20 participating Primary Health Organisations.
Findings
There has been substantial growth in the development of nursing roles for some nurses in general practice; however, this expansion has not been universal and one of the main reasons for this is the way funding devolves at the practice level. One of the consequences of the policymakers not taking into account the business model of the majority of general practices, is the resulting overarching goal of the strategy not being realised, and inequalities in health status remaining.
Coagulase-negative staphylococci (CoNS) are the most commonly isolated pathogens in the neonatal intensive care unit (NICU). CoNS infections are associated with increased morbidity, including neurodevelopmental impairment.
Objective.
To describe the epidemiology of CoNS infections in the NICU. To determine mortality among infants with definite, probable, or possible CoNS infections.
Methods.
We performed a retrospective cohort study of all blood, urine, and cerebrospinal fluid cultures from samples obtained from infants aged <121 postnatal days.
Setting.
A total of 248 NICUs managed by the Pediatrix Medical Group from 1997 to 2009.
Results.
We identified 16,629 infants with 17,624 episodes of CoNS infection: 1,734 (10%) definite, 3,093 (17%) probable, and 12,797 (73%) possible infections. Infants with a lower gestational age and birth weight had a higher incidence of CoNS infection. When controlling for gestational age, birth weight, and 5-minute Apgar score, we found that infants with definite, probable, or possible CoNS infection had lower mortality (odds ratio [OR], 0.74 [95% confidence interval {CI}: 0.61, 0.89], 0.68 [95% CI, 0.59, 0.79], and 0.69 [95% CI, 0.63, 0.76], respectively) compared with infants who had negative culture results (P<.001). No significant difference in overall mortality was found in infants who had definite CoNS infection compared with those who had probable or possible CoNS infection (OR, 0.93 [95% CI, 0.75, 1.16] and 0.85 [95% CI, 0.70, 1.03], respectively).
Conclusions.
CoNS infection was strongly related to lower gestational age and birth weight. Infants with clinical sepsis and culture-positive CoNS infection had lower mortality rates than infants with clinical sepsis and negative blood culture results. No difference in mortality between infants with a diagnosis of definite, probable, or possible CoNS infection was observed.
All good quality trials of psychological interventions need to check formally that therapists have used the techniques prescribed in the published therapy manuals, and that the therapy has been carried out competently. This paper reviews methods of assessing adherence and competence used in recent large-scale trials of Cognitive Behaviour Therapy (CBT) for psychosis in the UK carried out by our research groups. A combination of the Cognitive Therapy Rating Scale and specific versions of the Cognitive Therapy for Psychosis Adherence Scales provides an optimal assessment of adherence and competence. Careful assessment of the competence and adherence can help identify the procedures actually carried out with individuals within trials. The basic use of such assessments is to provide an external check on treatment fidelity on a sample of sessions. Such assessment can also provide the first step towards moving research towards making sense of CBT for psychosis as a complex intervention and identifying which techniques work for which problems of people with psychosis, at which stages of disorder?
Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone. Reported effects of exposure include changes in organ weight and gross structure, histology and gene and protein expression but these changes are not reflected in changes in reproductive performance under the conditions tested. These results illustrate the complexity of the effects of endocrine disrupting compounds on the reproductive axis, which make it difficult to extrapolate between, or even within, species. Effects of pollutant exposure on the thyroid gland, immune, cardiovascular and obesogenic systems have not been shown explicitly, in ruminants, but work on other species suggests that these systems can also be perturbed. It is concluded that exposure to a mixture of anthropogenic pollutants has significant effects on a wide variety of physiological systems, including the reproductive system. Although this physiological insult has not yet been shown to lead to a reduction in ruminant gross performance, there are already reports indicating that anthropogenic pollutant exposure can compromise several physiological systems and may pose a significant threat to both reproductive performance and welfare in the longer term. At present, many potential mechanisms of action for individual chemicals have been identified but knowledge of factors affecting the rate of tissue exposure and of the effects of combinations of chemicals on physiological systems is poor. Nevertheless, both are vital for the identification of risks to animal productivity and welfare.
This study shows for the first time, the correlation between the microstructural properties (chemical composition and its homogeneity) and the thermoelectric properties for p-type Bi0.5Sb1.5Te3 electroplated films (10-15 μm thickness). High microstructural quality of Bi0.5Sb1.5Te3 electroplated films (a close to stoichiometry chemical composition with its high homogeneity elements distribution) was achieved by using an additive in the plating solution (sodium ligninsulfonate) as a surfactant agent. A fine-grained microstructure of 280 nm to 1μm has been observed for these materials, which half that of the plated films without a surfactant. The thermoelectric properties of electrodeposited Bi0.5Sb1.5Te3 films obtained without microstructural optimisation, show modest Seebeck coefficient values of 20-120 μm/K, electrodeposited film with an optimised microstructure exhibits very high values of Seebeck coefficient of 220-300 μm/K.