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Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
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.
Introduction: Medical record review (MRR) studies are commonly used in Emergency Medicine (EM) research. It is not always clear how sample size calculations are reported, or the methods by which they were derived. This scoping review sought to examine reporting and justification of MRR sample sizes from the EM literature. Methods: Using Web of Science, we identified the top ten journals, based on impact factor rating in 2018, within the field of Emergency Medicine. Journals were excluded if they were not in English or did not include sufficient articles for analysis. Within each of these ten selected journals, we searched for chart reviews and related terms: "medical record", "outpatient record", "inpatient record", "clinical record", and "nursing note". From this search subset, five articles were randomly selected from each journal. Data about sample size and sample size selection were extracted and analyzed by two reviewers independently for each article. Results: Of the 50 articles randomly selected, 48 articles were retrospective MRRs and two articles were prospective MRRs. 78% (39 articles) chose sample size based on availability, 14% (seven articles) chose sample size based on power calculations, 4% (two articles) chose sample size based on a previous study's methodology, and 4% (two articles) did not give details on sample size selection. Conclusion: While some emergency medicine MRRs based sample size selection on power or previous studies, the vast majority are based on availability with study-specific exclusion/inclusion criteria. This may indicate they are using a smaller sample size than necessary to be sufficiently powered to assess their end goal. More work is required to determine the effect of this on outcomes and interpretability of results, as well as which method is most accurate and efficient.
The term auditory verbal hallucination (AVH) covers a diverse phenomenological experience. One model of AVHs proposes they result from self-monitoring deficits causing inner speech to be experienced as alien. The experimental evidence for such a model is briefly summarised. The fit of inner speech models with the phenomenology of AVHs is then critically examined. The form, function, and development of private and inner speech is discussed, and contrasted with the phenomenology of a range of AVHs. It is argued that only a subset of AVHs are phenomenologically consistent with inner speech models. Implications for the study of AVHs are discussed.
ICD-10 delineates Acute and Transient Psychotic Disorders (ATPD, F 23) as distinct from schizophrenia and affective psychosis. We investigated the descriptive epidemiology of ATPD and predictive validity of the diagnosis, compared its three-year outcomes with affective psychosis and schizophrenia, and explored whether acute onset and early remission identify a distinct good outcome subgroup in non-affective psychoses.
Between 1992-1994, all first-episode psychosis patients in Nottingham were identified and assigned an intake ICD-10 diagnosis. Patients were assessed three years later using established outcome measures and longitudinal diagnosis assigned. Multivariate analyses were conducted to determine whether acute onset and early remission predicted favourable three-year outcome in non-affective psychotic disorders.
Of 168 cases of first-episode psychosis, 112 received an intake diagnosis of non-affective psychoses (F20-29) and 32 (19%) of ATPD (F23). ATPD diagnosis was stable in women over three years, but not in men. Outcomes of ATPD were better than schizophrenia and similar to affective psychosis. In non-affective psychoses, favourable outcomes were a function of gender and good premorbid functioning rather than acute onset and early remission.
ICD-10 ATPD criteria identify a diagnostically unstable group of disorders consisting of ‘good outcome’ schizophrenia, affective psychosis and a very small group of ‘true’ non-affective, non-schizophrenic acute and transient psychoses. Although ATPD have a better outcome than schizophrenia, in non-affective psychoses, acute onset and early remission do not independently predict favourable outcome over three years.
To investigate the feasibility, and patient/psychiatrist acceptability, of an SMS text messaging system reminding patients receiving quetiapine to take their medication.
8-12(mean:9.4) week, non-interventional, psychiatrist assessed, pilot study of 27 outpatients receiving quetiapine (mean age[range]: 35.3[19-57] years). Patients were asked to reply to SMS messages sent twice daily to their cellular phone to remind them to take their medication (morning) and enquire about their well-being (evening). Patients' response (morning-yes/no; evening-positive/negative/neutral) was monitored by psychiatrists (n=7) via a website, and subsequently used to assess technical feasibility. Psychiatrists rated acceptability and feasibility of the system by completing case report forms (CRFs). Data are from the LOCF population.
Patients responded to 77% (compliance) of the 5,000 SMS messages sent (84% correctly, 13% inaccurately, 3% responded late [eg, day after]). 7/27 patients withdrew prematurely. The most common benefits expressed by patients were that they felt cared for (n=11/21) and were reminded to take their medication (n=7/21). Psychiatrists' ratings of the system improved over time, with SMS compliance and increased patient contact seen as the most valuable aspects. At study end, CRF data showed psychiatrists felt the system was valuable to 19/22 patients, 16/24 patients remained compliant with the system and 16/22 patients felt the frequency of SMS messages was acceptable. There was a strong correlation between patients giving positive well-being responses and SMS compliance (R Pearson=0.72, p<0.001).
The high levels of SMS compliance and benefits expressed by patients and psychiatrists support a larger-scale assessment of this system.
Among the 10 categories of personality disorders (PDs), interventions for antisocial and borderline personality disorder are best studied. However, the remaining PDs also pose major problems in everyday health care settings. People affected often additionally present with Axis-I disorders such as substance-related, mood or anxiety disorders, and are among those most difficult to treat. Cluster A PDs (paranoid, schizoid, schizotypal) are of particular significance as some authors argue that they may be part of a continuum of mental disorders and be considered as sub-syndrome of schizophrenia
In the context of Cochrane Collaboration reviews for Cluster A, B and C PDs, exhaustive literature searches were completed to identify the current RCT evidence for PD treatments. Retrievals were assessed and evaluated by two reviewers independently and trials for Cluster A PD were identified.
Only very few (under five) RCTs specifically for Cluster A PDs were identified. Some studies reported on mixed PD samples but it was not always possible to extract data specifically for Cluster A disorders. Participants mostly also suffered from Axis-I disorders. Reported outcomes also focus on Axis-I disorder outcomes or general measures such as overall functioning rather than specific PD symptoms.
The current evidence for psychpathological treatment of Cluster A PD is sparse and does not allow for distinct treatment recommendations. Symptom-driven treatment regimes as suggested by several guidelines are not supported by current evidence.
Limited to no literature exists on the association among sleep quality, obesity and depression in pediatric populations. This study aims to explore this association by examining the sleep quality of children and adolescents before and after a twelve-week comprehensive multidisciplinary pediatric obesity program.
Archival data from the pediatric obesity program included 71 children ages 6-17 (M=10.24, SD=2.74 ) who had been assessed pre and post intervention using the Children's Depression Inventory (CDI), a Sleep Questionnaire, and physician derived Body Mass Index (BMI). On all measures, higher scores indicate presence of symptoms of depression, sleep difficulties, or obesity.
High scores on the CDI proved to predict poor sleep quality both at intake and exit. Hierarchical regression exhibited change in BMI from intake to exit and predicted sleep quality. As BMI decreased from intake to exit, sleep quality increased.
The current study suggests that sleep quality is influenced by the level of depression in children and adolescents both at pre and post intervention measures. Both depression and BMI influenced sleep quality. When the effect of BMI was accounted for, depression significantly predicted sleep quality. The more depressed children/adolescents reported to be, the lower their quality of sleep. Thus, this study suggests the importance of sleep and depression in the treatment of pediatric obesity. This research supports the importance of a multidisciplinary approach to addressing pediatric obesity.
Psychiatry in the UK has longstanding recruitment problems (1). Evidence suggests the positive effects of clinical attachments on attitudes towards psychiatry are often transient (2). We therefore created the Psychiatry Early Experience Programme (PEEP) where year 1 medical students are paired with psychiatry trainees and shadow them at work. Students will ideally remain in PEEP throughout medical school, providing consistent exposure to psychiatry and a broad experience of its subspecialties.
1. To present PEEP
2. To assess:
a. Students’ baseline attitudes to psychiatry
b. PEEPs’ impact on students’ attitudes to psychiatry
A prospective survey based cohort study of King’s College London medical students.
PEEP started in 2013. In this cohort all students that signed up were accepted.
Students’ attitudes towards psychiatry were assessed on recruitment using the ATP-30 questionnaire (3), and will be re-assessed annually.
127 students were recruited. Attitudes were positive overall. 73% listed psychiatry in their top three specialities. 95.3% agreed or strongly agreed that ‘psychiatric illness deserves at least as much attention as physical illness.’ 84.3% disagreed or strongly disagreed that ‘at times it is hard to think of psychiatrists as equal to other doctors.’
Baseline attitudes to psychiatry were positive. By March 2015 we aim to collect and analyse data on students’ attitudes after one year in PEEP. Through on-ongoing analysis of this and future cohorts, we aim to assess the impact of PEEP on improving attitudes to psychiatry and whether this will ultimately improve recruitment.
Cannabis is a widely used drug, which effects on human health remain controversial. Recent studies have found correlations between cannabis use and brain structural changes that may be related to ageing processes. Eotaxin-1 is a chemokine described as a marker of ageing, which also appear to increase with cognitive deficits and neurogenesis. Here, we aimed at characterising the effect of cannabis in accelerating normal ageing processes, by studying eotaxin-1 plasma levels in people who currently use cannabis, have used cannabis in the past, or have never used cannabis.
A total of 87 healthy volunteers participated in the study. Participants completed the Cannabis Experience Questionnaire, the General Practice Physical Activity Questionnaire, the Sociodemographic, Morphometric, Alcohol and Tobacco Questionnaire, and provided a blood sample. Eotaxin-1 was assessed by ELISA. The three groups were compared using one-way ANOVA to assess levels of eotaxin-1, and nonpaired Student t-tests to assess other factors effects.
Current users of cannabis (n=18) had significantly higher eotaxin-1 plasma levels compared to past users of cannabis (n=33) and individuals who never used cannabis (n=36). The latter two groups had similar eotaxin-1 levels. Higher eotaxin-1 plasma levels were not attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs.
These results suggest that cannabis use increases eotaxin-1 plasma levels and could result in accelerated brain ageing. However, the effects appear to be reversible when cannabis use ceases. These findings have important implications for treatment and care of mental health disorders, such as schizophrenia.
There are limited amount of studies comparing time trends of incidence and risk factors of psychosis.
To compare time trends of incidence of psychosis in two population samples.
To study 1) onset age and cumulative incidence of psychoses in two Northern Finland Birth Cohorts (NFBC), 2) changes in type of diagnosis and risk factors.
The NFBC 1966 (N=12,058) and NFBC 1986 (N=9,432) are prospective cohorts of the two provinces of Finland with the live born children followed since pregnancy. The data for psychosis and risk factors were collected from variety of nationwide registers and earlier collected data of the NFBCs. The follow-up time was in both cohorts in average 26.5 years.
Proportion of all psychoses was higher in NFBC 1986 than in the NFBC 1966 (1.81% vs 1.0%). There were more affective psychoses in NFBC 1986 (0.5% vs 0.1%), but incidence of schizophrenia was the same (0.4%) in both cohorts. The age of onset was lower in NFBC 1986 than in NFBC 1966 and majority of this cases were females. Only parental psychosis was a significant risk factor predicting psychosis (Hazard Ratios >3.0) in both cohorts.
In conclusion, two birth cohorts within 20 years covering altogether about 40 years showed changes in terms of incidence, age of onset, and type of psychosis.
The diagnostic criteria of delayed-onset PTSD is that the onset of PTSD symptoms should occur at least 6 months after the traumatic event (DSM-IV; American Psychiatric Association, 2000). In a meta analysis across 11 countries, 25% of all PTSD cases were classified as delayed-onset PTSD (Smid et al., 2009). Existing research on delayed-onset PTSD has predominantly used US data, with a dearth of prospective research in UK military samples.
This study investigated the prevalence of delayed-onset PTSD in UK military personnel and examined the socio-demographic, military and psychological characteristics of delayed-onset PTSD.
The sample comprised 1397 participants from a two phase prospective cohort study of UK military personnel. Delayed-onset PTSD was categorised as participants who did not meet the criteria for probable PTSD (assessed by the PCL-C) at phase 1, but who met the criteria by phase 2.
3.5% of participants met the criteria for delayed-onset PTSD. Subthreshold PTSD, common mental disorder (CMD), poor/fair self-reported health and multiple physical symptoms at phase 1, and the onset of alcohol misuse or CMD between phases 1 and 2, were associated with delayed-onset PTSD.
Delayed-onset PTSD exists in this UK military sample. Military personnel who developed delayed-onset PTSD were more likely to have psychological ill-health at an earlier assessment and clinicians should be aware of potential co-morbidity in these individuals, including alcohol misuse. Leaving the military, or experiencing relationship breakdown, was not associated.
Schizophrenia is a serious mental illness that carries a significant burden for families providing care.
The ADHES carers' survey canvassed opinions of families/friends of patients with schizophrenia across Europe.
To ascertain carer attitudes towards schizophrenia, its treatment and treatment adherence.
The survey was conducted from January-April 2011 in 16 European countries, comprising 10 questions relating to the respondents' understanding of schizophrenia, attitudes towards schizophrenia treatments, and perception of the family's/friend's role in supporting patients with schizophrenia.
Results were obtained from 138 respondents. 76% of carers recognized the importance of medication to help patients get better, improve their quality of life (77%) and relationships (74%). 67% of carers responded that they believed schizophrenia treatment damages patients' general health. Two-thirds of the carers reported that treatment adherence was a burden for the patient and over a third of carers indicated that it was a daily struggle to get patients to take their medication. 50% of carers considered the benefits offered by long-acting injectable antipsychotics as very/quite important and thus, could provide a valuable tool in improving treatment adherence. 92% of carers agreed on the importance of family support to boost treatment adherence with education/information deemed important for families and patients alike.
Carers recognize the issues they face in caring for patients with schizophrenia and their role in improving partial/non-adherence to medication, especially to avoid suboptimal treatment outcomes. The important role of family carers should be considered by healthcare professionals when treating patients with schizophrenia.
Evaluation of knowledge on Section 136 of mental health act in Police officers in Cheshire
Section 136 allows a Constable to remove a mentally disordered person from a public place to a place of safety for up to 72 hours. There has been an increasing rise in the use of section 136 of mental health act with recent reviews showing that in 2005-2006 there were 11000 detentions under section 136 in police stations and about 5500 detentions in hospitals. More recent data has shown a significant increase in the number of those detained under Section 136 in hospital. The data for England found 7035 such assessments in 2007 rising in successive years to 8495 and 12038 (Care Quality Commission, 2010). In this context it would be imperative to evaluate the knowledge on Section 136 of mental health act amongst the police personnel. Only one relevant study was found after an extensive literature search in this domain and this showed that the knowledge among the police on this area was poor (Lynch et al 2001)
A structured questionnaire based on code of practice of mental health law on section 136 was outlined. Mental health law experts and legislators have been consulted in formulation of this questionnaire. This questionnaire has been distributed within the police force of Warrington city, Cheshire.
Result & Conclusions
The results are still awaited but would be obtained in few weeks time and this could be sent over to the submission Panel as addendum.
Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia.
Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression.
Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition.
Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.