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A British general adult psychiatrist born and trained in the UK, who also considers himself Pakistani, had the opportunity to spend 2 weeks running a psychiatric clinic in a remote hospital in the Punjab province of Pakistan. In this article he offers some reflections on the unexpected culture shock he felt, on the hospital system, the patients he treated and their resilience in such a poor country.
The audit was undertaken to explore if inpatients with treatment resistant schizophrenia (TRS), or whose condition has not adequately responded to two antipsychotics of an optimal duration and dose, were offered clozapine as per NICE guidelines (CG178 18.104.22.168).
Data were collected retrospectively and anonymously from all electronic notes via the UK-CRIS analysis platform.
The inclusion criteria required patients, aged 18–64 years, to have a schizophrenia (ICD10 F20) diagnosis and to have been admitted to one of ten Trust inpatient wards between 01/01/2020 and 01/01/2021.
Patients were required to fulfil the criteria of treatment resistance, as having an inadequate response to two or more antipsychotic drugs, one of which was an atypical agent.
Patients who had previously tried or were currently on clozapine were excluded. Those with non-schizophrenia psychotic disorders were also excluded. 347,645 records were electronically screened according to the criteria, and 209 records were reviewed.
43 patients from the 209 patients reviewed were found to be eligible for clozapine. 28 (65%) were offered clozapine during their admission and 9 of these patients had started the titration process (21% of those eligible).
Of the 19 patients who declined clozapine when offered, 14 had refused the drug with the most common reason of not accepting the required blood monitoring (n=10).
Of the 15 eligible patients who were not offered clozapine, the clinical team had documented a consideration to offer clozapine in 6 patients (14%) but had rejected its, predominantly due to concerns of non-compliance.
For 3 patients (7%) the clinical team considered for but did not offer clozapine. There was no documentation regarding clozapine for 6 patients (14%).
This audit identified that most patients with TRS were offered clozapine during their admission. However, a proportion of patients were not offered the gold standard treatment for TRS and this may lead to poorer outcomes.
It demonstrated that a minority of eligible patients ultimately start the drug. There are barriers for eligible patients to accept clozapine, for instance around the regular blood monitoring required.
Many patients with psychosis symptoms and schizophrenia use cannabis as a recreational drug. Patients who use cannabis respond differently to antipsychotic treatment compared to those who do not. Despite this, there is a lack of evidence, and therefore clinical guidance, pertaining to the best pharmacological treatment to improve psychosis or cannabis use in this population. This systematic review was carried out to assess the current evidence base regarding the most effective pharmacological treatment for patients with psychosis who also have a background of using cannabis. Our specific question was: ‘in patients with a dual diagnosis of psychosis and cannabis use, which pharmacological interventions have the most efficacy in improving psychosis or reducing cannabis use?’.
A search of EMBASE, PsychINFO, and MEDLINE(R) databases was carried out on September 30, 2020. Bibliographies of other studies were also searched for relevant articles. After exclusion of any articles which did not meet inclusion criteria for this review, eleven full texts remained; a qualitative analysis was carried out on these, but there was no meta-analysis. Only randomised control trials (RCTs) whose interventions and controls were pharmacological therapies, and which included patients with a background of cannabis use and psychosis, and which measured clinical outcomes, were included.
We found 11 articles which analysed 10 RCT studies (n = 363) investigating risperidone, olanzapine, clozapine, haloperidol, ziprasidone and imipramine. 6/11 were double blind. The studies were small in size, varied in their methodology, exact inclusion criteria, exact outcomes, and all had a high risk of bias. Few significant findings were found. There is limited evidence for clozapine having anti-craving effect however whether this is associated with reduction in use remains to be demonstrated. We found no studies of adjunctive anticonvulsant agents, which are often used in psychotic disorders.
This review underlines the paucity of studies on which to make evidence-based decisions. No new studies have been undertaken since the last systematic review in this area in the last 7 years. Due to the lack of high-quality evidence found by this review, there remains a considerable need for interventional, high-quality RCTs in this comorbid patient group.
Anxiety and depressive symptoms are frequent in people with alcohol use disorders (AUDs) (approximately 55%) and are associated with worse outcomes. Current interventions to treat mood symptoms in alcohol-dependent adults, including psychosocial therapies, anxiolytics and antidepressants have shown limited benefits to date. The efficacy of anticonvulsants and antipsychotics have been studied but never previously systematically reviewed. We aimed to assess the efficacy of anticonvulsants and antipsychotics in treating anxiety and depressive symptoms in alcohol-dependent adults.
A literature search of MEDLINE, EMBASE and PsycINFO was performed through October 2020 to identify all English-language articles of double-blinded randomised controlled trials that included adults with AUDs who were treated with an anticonvulsant or antipsychotic for at least four weeks. A combination of search terms was used to describe the AUDs, study medications and the primary outcome. Participants with other psychiatric disorders were excluded. Mean changes in anxiety and depressive scores were evaluated in addition to the adverse events and withdrawal rates. The risk of bias of each study was also assessed.
Of 393 citations identified, 23 studies (2823 participants) met the inclusion criteria. Eighteen studies examined ten different anticonvulsants, while five studies examined two antipsychotics. The heterogeneity between the trials' methodology led to conflicting results; however, as the low-quality trials were excluded, the majority agreed that anticonvulsants and antipsychotics were not superior in moderating anxiety and depressive symptoms of alcohol-dependent adults. All antipsychotics were safe and well-tolerated, but adverse events were associated with several anticonvulsants (high dose baclofen, gabapentin, topiramate and valproate).
Current information on anticonvulsants and antipsychotics is insufficient to extrapolate the benefits of treating anxiety and depressive symptoms in alcohol-dependent adults. Further research must be conducted into improving the quality of reporting and understanding the comorbidity's underlying mechanism, and alternative treatment approaches.
There is mounting evidence to implicate the intrauterine environment as the initial pathogenic stage for neuropsychiatric disease. Recent developments in magnetic resonance imaging technology are making a multimodal analysis of the fetal central nervous system a reality, allowing analysis of structural and functional parameters. Exposures to a range of pertinent risk factors whether preconception or in utero can now be indexed using imaging techniques within the fetus’ physiological environment. This approach may determine the first “hit” required for diseases that do not become clinically manifest until adulthood, and which only have subtle clinical markers during childhood and adolescence. A robust characterization of a “multi-hit” hypothesis may necessitate a longitudinal birth cohort; within this investigative paradigm, the full range of genetic and environmental risk factors can be assessed for their impact on the early developing brain. This will lay the foundation for the identification of novel biomarkers and the ability to devise methods for early risk stratification and disease prevention. However, these early markers must be followed over time: first, to account for neural plasticity, and second, to assess the effects of postnatal exposures that continue to drive the individual toward disease. We explore these issues using the schizophrenia spectrum disorders as an illustrative paradigm. However, given the potential richness of fetal magnetic resonance imaging, and the likely overlap of biomarkers, these concepts may extend to a range of neuropsychiatric conditions.
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
Evidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined.
We undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use.
Cessation of cannabis use was associated with greater psychotic-like experiences [p < 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179–1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p < 0.001, Exp(B) 0.717, 95% CI 0.662–0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p < 0.003, Exp(B) 1.131, 95% CI 1.044–1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p < 0.015, Exp(B) 0.892, 95% CI 0.814–0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences.
Elucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.
Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials.
We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched.
We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage.
Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.
To study (i) the current prevalence of iodine-deficiency disorders among schoolchildren in south-western Saudi Arabia after universal salt iodization and (ii) the iodine content of table salts and water.
Cross-sectional study on a stratified proportional allocation sample of children. Thyroid gland enlargement was assessed clinically and by ultrasound scanning. Urine, table salt and water samples were taken to measure iodine content.
The Aseer region, south-western Saudi Arabia.
Schoolchildren aged 8–10 years.
The study included 3046 schoolchildren. The total goitre rate amounted to 24·0 %. Prevalence of enlarged thyroid by ultrasound was 22·7 %. The median urinary iodine concentration of the study sample amounted to 17·0 µg/l. The iodine content of table salt ranged from 0 to 112 mg/kg; 22·5 % of the table salt samples were below the recommended iodine content (15 mg/kg) set by WHO. The total goitre rate increased significantly from 19·8 % among children using table salt with iodine content ≥15 mg/kg to reach 48·5 % among children using table salt with 0 mg iodine/kg. Analysis of water samples taken from schools showed that the majority of water samples (78·8 %) had an iodine content of 0 µg/l.
The study documented that 18 years after the national study, and after more than a decade of universal salt iodization in Saudi Arabia, the problem of iodine-deficiency disorders is still endemic in the Aseer region. Efforts should focus on fostering advocacy and communication and ensuring the availability of adequately iodized salt.
The anxiety disorders are a prevalent mental health problem in older age with a considerable impact on quality of life. Until recently there have been few longitudinal studies on anxiety in this age group, consequently most of the evidence to date has been cross-sectional in nature.
We undertook a literature search of Medline, PsycINFO, the Cochrane trials database and the TRIP medical database to identify longitudinal studies which would help elucidate natural history and prognosis of anxiety disorders in the elderly.
We identified 12 papers of 10 longitudinal studies in our Review. This represented 34,691 older age participants with 5,199 with anxiety disorders including anxious depression and 3,532 individuals with depression without anxiety. Relapse rates of anxiety disorders are high over 6 year follow-up with considerable migration to mixed anxiety-depression and pure depressive mood episodes. Mixed anxiety-depression appears to be a poorer prognostic state than pure anxiety or pure depression with higher relapse rates across studies. In community settings treatment rates are low with 7–44% of the anxious elderly treated on antidepressant medications.
To our knowledge this is the first Systematic Review of longitudinal trials of anxiety disorders in older people. Major longitudinal studies of the anxious elderly are establishing the high risk of relapse and persistence alongside the progression to depression and anxiety depression states. There remains considerable under-treatment in community studies. Specialist assessment and treatment and major public health awareness of the challenges of anxiety disorders in the elderly are required.
Panonychus ulmi (Koch) and Bryobia rubrioculus (Scheuten) are very serious pests on apple trees in Lebanon. The effectiveness of M2060 (2 fluoroethyl (4-biphenylyl) acetate), Ovamort, Diotol, Genite, and Citronol plus parathion was investigated on the winter eggs of these two mites in the laboratory and in the field. M2060-oil was highly effective and superior to all products at early and late dormant stages of tree growth. The nearer to egg hatch the other products were applied, the more effective they were.
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