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The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES.
This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines.
Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1–30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3–58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49–28.68). Correlates of depressive psychopathology were also found.
At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention – regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.
Intellectual disability and autism spectrum disorder (ASD) influence the interactions of a person with their environment and generate economic and socioeconomic costs for the person, their family and society.
To estimate costs of lost workforce participation due to informal caring for people with intellectual disability or autism spectrum disorders by estimating lost income to individuals, lost taxation payments to federal government and increased welfare payments.
We used a microsimulation model based on the Australian Bureau of Statistics' Surveys of Disability, Ageing and Carers (population surveys of people aged 15–64), and projected costs of caring from 2015 in 5-year intervals to 2030.
The model estimated that informal carers of people with intellectual disability and/or ASD in Australia had aggregated lost income of AU$310 million, lost taxation of AU$100 million and increased welfare payments of AU$204 million in 2015. These are projected to increase to AU$432 million, AU$129 million and AU$254 million for income, taxation, and welfare respectively by 2030. The income gap of carers for people with intellectual disability and/or ASD is estimated to increase by 2030, meaning more financial stress for carers.
Informal carers of people with intellectual disability and/or ASD experience significant loss of income, leading to increased welfare payments and reduced taxation revenue for governments; these are all projected to increase. Strategic policies supporting informal carers wishing to return to work could improve the financial and psychological impact of having a family member with intellectual disability and/or ASD.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
The brain endocannabinoid system is believed to play significant roles in anti-nociception, fear response, anxiety, and stress. This study investigated the effects of rat inguinal surgery on the levels of endocannabinoids in the cerebral cortex.
The aim of this study was to investigate the effects of acute post-surgical pain on the levels of endocannabinoids in the cerebral cortex.
Quantitation of endocannabinoids in the rat cerebral cortex was performed by liquid chromatography–tandem mass spectrometry.
There was no significant difference in the cerebral cortical levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) between the sham and surgery experimental groups. However, there were lateralized differences in the levels of these endocannabinoids between the right and left cerebral cortices irrespective of the two groups. The concentrations of AEA and 2-AG were significantly higher in the right cerebral cortex compared to the contralateral cerebral cortex.
Acute post-surgical pain did not induce significant alterations in the cerebral cortical levels of endocannabinoids in this study, but the phenomenon of lateralization of the cerebral cortical AEA and 2-AG levels was observed; this latter finding may be related to the role played by endocannabinoids in fear conditioning.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14–26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes.
In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
Advance care planning (ACP) is identified as being an important process for people with dementia. However, its efficacy for improving outcomes relevant for the individual, carers and the health system has yet to be established.
We conducted a systematic review with the aims of testing the efficacy of ACP for people with dementia and describing the settings and population in which it has been evaluated.
A search was completed of electronic databases in August 2016. Articles were included if they described interventions aimed at increasing planning for future care of people with dementia, delivered to the person with dementia, their carers and/or health professionals.
Of 4,772 articles returned by searches, 30 met the inclusion criteria, testing interventions in nursing home (n= 16) community (n = 10) and acute care (n = 4) settings. Only 18 interventions directly involved the person with dementia, with the remainder focusing on surrogate decision-makers. In all settings, interventions were found effective in increasing ACP practice. In nursing homes, ACP was found to influence care and increase the concordance between end of life wishes and care provided. Interventions in the community were found to improve patient quality of life but were not shown to influence concordance.
Future research should focus on ways to involve people with dementia in decision-making through supported means.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Background: Although previous research has suggested that patients with incidentally discovered low-grade gliomas (iLGG) who undergo surgery prior to the appearance of symptoms have improved outcomes compared to those who are symptomatic, an ideal approach to managing iLGG is not well-established. The purpose of this systematic review is to identify all cases of iLGG in the literature and characterize the effect of the timing of surgery on survival. Methods: We searched EMBASE, MEDLINE, and PubMed for articles related to iLGG. After duplicates were removed, the articles were then screened based on strict inclusion and exclusion criteria. Results: We retrieved 24/1377 unique articles with a total of 175 patients who underwent surgery for iLGG prior to symptoms appearing. The average age was 29.1yrs (range 1-62) and the mean follow-up period was 56 months (range 1-234months). Unfortunately, only 6/24 articles reported progression-free survival (average 32.4months) and only 1/24 reported 10-year survival. Conclusions: The articles we identified favored an early intervention for iLGG, however, there was a considerable lack of long-term follow-up and survival data to justify such a claim. Further studies need to be performed with adequate follow-up data in order to determine the optimal timing of surgical intervention for these patients.
Introduction: Influenza is a preventable infectious disease that causes a yearly burden to Canada. While an influenza vaccine is available free of charge in most provinces, uptake is below target rates. 15% of Canadians who did not get the influenza vaccine reported that they “didn't get around to it”; this presents an opportunity to combine the task of influenza prevention with the logistical issue of another health system challenge: escalating emergency department (ED) wait times. At the Queen Elizabeth II Health Sciences Centre (QEII) in Halifax, NS, average wait time is 4.6 hours. Offering the influenza vaccine during this time could increase convenient access to health services, and ultimately, improve vaccination rates. Methods: This observational, cross-sectional design study is currently in progress. It aims to gauge public interest, health care provider (HCP) support, perceived barriers and perceived facilitators to influenza vaccine availability at the QEII ED. Data is being collected via short, anonymous, close-ended questionnaires over a 7-week period, set to end Dec 14, 2018. Client participants are a convenience sample of low-acuity (Canadian Triage and Acuity Scale score 4/5), adult clients who use the QEII ED during the study period, anticipated n = 150. Client questionnaires are completed, with the help of a research assistant, on an iPad that inputs data directly into a secure online data collection tool. The HCP group is a convenience sample of nurses, physicians and paramedics currently working in the QEII ED, anticipated n = 80. Questionnaires are available to HCPs either on paper outside the staff lounge, or online. Data is being collected via short, anonymous, close-ended questionnaires over a 7-week period, set to end Dec 14, 2018. Client participants are a convenience sample of low-acuity (Canadian Triage and Acuity Scale score 4/5), adult clients who use the QEII ED during the study period, anticipated n = 150. Client questionnaires are completed, with the help of a research assistant, on an iPad that inputs data directly into a secure online data collection tool. The HCP group is a convenience sample of nurses, physicians and paramedics currently working in the QEII ED, anticipated n = 80. Questionnaires are available to HCPs either on paper outside the staff lounge, or online. Results: Following completion of data collection, descriptive statistics, such as the frequency of support for ED influenza vaccination and the proportion of unvaccinated clients willing to receive the vaccine if available in the ED, will be calculated using IBM SPSS Statistics 25. This will provide meaningful data that can be used by the QEII to inform future program planning (i.e. should the influenza vaccine be made available in the ED). Conclusion: An ED vaccination program could add value to the hours clients spend waiting to be seen, and make ED care more cohesive. It is essential that clients and ED staff are approached prior to any new initiative; this study is one way we can lay the necessary groundwork for a public health program that would utilize patient “wait time” more effectively.
Synthetic biology has a huge potential to produce the next generation of advanced materials by accessing previously unreachable (bio)chemical space. In this prospective review, we take a snapshot of current activity in this rapidly developing area, focusing on prominent examples for high-performance applications such as those required for protective materials and the aerospace sector. The continued growth of this emerging field will be facilitated by the convergence of expertise from a range of diverse disciplines, including molecular biology, polymer chemistry, materials science, and process engineering. This review highlights the most significant recent advances and addresses the cross-disciplinary challenges currently being faced.
Background: Safety behaviours are ubiquitous across anxiety disorders and are associated with the aetiology, maintenance and exacerbation of anxiety. Cognitive behavioural models posit that beliefs about safety behaviours directly influence their use. Therefore, beliefs about safety behaviours may be an important component in decreasing safety behaviour use. Unfortunately, little empirical research has evaluated this theorized relationship.
Aims: The present study aimed to examine the predictive relationship between beliefs about safety behaviours and safety behaviour use while controlling for anxiety severity.
Method: Adults with clinically elevated levels of social anxiety (n = 145) and anxiety sensitivity (n = 109) completed an online survey that included established measures of safety behaviour use, quality of life, and anxiety severity. Participants also completed the Safety Behaviour Scale (SBS), a measure created for the current study which includes a transdiagnostic checklist of safety behaviours, as well as questions related to safety behaviour use and beliefs about safety behaviours.
Results: Within both the social anxiety and anxiety sensitivity groups, positive beliefs about safety behaviours predicted greater safety behaviour use, even when controlling for anxiety severity. Certain beliefs were particularly relevant in predicting safety behaviour use within each of the clinical analogue groups.
Conclusions: Findings suggest that efforts to decrease safety behaviour use during anxiety treatment may benefit from identifying and modifying positive beliefs about safety behaviours.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.