Reflections on how to approach early career psychiatrist roles and challenges.

OBJECTIVE: To reflect upon and provide experiential advice to address the roles of early career psychiatrists. The main roles include leading patient care; working in teams; clinical supervision and governance of trainees, and of the psychiatrist by clinical directors/managers. While these roles vary across public and private sectors, the discussion focuses on common elements. CONCLUSIONS: The first several years of an early career psychiatrist's work often involves roles for which formal training cannot provide direct guidance, and which benefit from planning and reflective practice. Learning how to navigate clinical care, clinical supervision and governance, formal/informal mentoring and peer review are necessary to effective practice.

Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review.

BACKGROUND: Dementia is a debilitating syndrome that significantly impacts individuals over the age of 65 years. There are currently no disease-modifying treatments for dementia. Impairment of nutrient sensing pathways has been implicated in the pathogenesis of dementia, and may offer a novel treatment approach for dementia. AIMS: This systematic review collates all available evidence for Food and Drug Administration (FDA)-approved therapeutics that modify nutrient sensing in the context of preventing cognitive decline or improving cognition in ageing, mild cognitive impairment (MCI), and dementia populations. METHODS: PubMed, Embase and Web of Science databases were searched using key search terms focusing on available therapeutics such as 'metformin', 'GLP1', 'insulin' and the dementias including 'Alzheimer's disease' and 'Parkinson's disease'. Articles were screened using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). The risk of bias was assessed using the Cochrane Risk of Bias tool v 2.0 for human studies and SYRCLE's risk of bias tool for animal studies. RESULTS: Out of 2619 articles, 114 were included describing 31 different 'modulation of nutrient sensing pathway' therapeutics, 13 of which specifically were utilized in human interventional trials for normal ageing or dementia. Growth hormone secretagogues improved cognitive outcomes in human mild cognitive impairment, and potentially normal ageing populations. In animals, all investigated therapeutic classes exhibited some cognitive benefits in dementia models. While the risk of bias was relatively low in human studies, this risk in animal studies was largely unclear. CONCLUSIONS: Modulation of nutrient sensing pathway therapeutics, particularly growth hormone secretagogues, have the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.

Repurposing Proteostasis-Modifying Drugs to Prevent or Treat Age-Related Dementia: A Systematic Review.

Background: Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be therapeutically targeted to improve patient outcomes. This review aimed to collate all current evidence of the potential for targeting proteostasis with repurposed drugs as an intervention for age-related dementia and cognitive decline. Methods: PubMed, Web of Science and Embase databases were searched from inception until 4th July 2017 for studies published in English. Interventional studies of repurposed proteostasis-modifying drugs in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body disease, vascular dementia, and cognitive aging, in either animal models or humans with change in cognition as the outcome were included. The SYRCLE and Cochrane tools were used to assess risk of bias for included studies. Results: Overall 47 trials, 38 animal and 9 human, were isolated for inclusion in this review. Drugs tested in animals and humans included lithium, rapamycin, rifampicin, and tyrosine kinase inhibitors. Drugs tested only in animals included Macrophage and Granulocyte-Macrophage Colony Stimulating Factors, methylene blue, dantrolene, geranylgeranylacetone, minocycline and phenylbutyric acid. Lithium (n = 10 animal, n = 6 human) and rapamycin (n = 12 animal, n = 1 human) were the most studied proteostasis modifying drugs influencing cognition. Nine of ten animal studies of lithium showed a statistically significant benefit in Alzheimer's models. Rapamycin demonstrated a significant benefit in models of vascular dementia, aging, and Alzheimer's, but may not be effective in treating established Alzheimer's pathology. Lithium and nilotinib had positive outcomes in human studies including Alzheimer's and Parkinson's patients respectively, while a human study of rifampicin in Alzheimer's failed to demonstrate benefit. Microdose lithium showed a strongly significant benefit in both animals and humans. While the risk of bias was relatively low in human studies, the risk of bias in animal studies was largely unclear. Conclusion: Overall, the collective findings support the hypothesis that targeting proteostasis for treatment of dementia may be beneficial, and therefore future studies in humans with repurposed proteostasis modifying drugs are warranted. Larger human clinical trials focusing on safety, efficacy, tolerability, and reproducibility are required to translate these therapeutics into clinical practice.

Reducing the complexity of an agent-based local heroin market model.

This project explores techniques for reducing the complexity of an agent-based model (ABM). The analysis involved a model developed from the ethnographic research of Dr. Lee Hoffer in the Larimer area heroin market, which involved drug users, drug sellers, homeless individuals and police. The authors used statistical techniques to create a reduced version of the original model which maintained simulation fidelity while reducing computational complexity. This involved identifying key summary quantities of individual customer behavior as well as overall market activity and replacing some agents with probability distributions and regressions. The model was then extended to allow external market interventions in the form of police busts. Extensions of this research perspective, as well as its strengths and limitations, are discussed.

A digital network approach to infer sex behavior in emerging HIV epidemics.

PURPOSE: Improve the ability to infer sex behaviors more accurately using network data. METHODS: A hybrid network analytic approach was utilized to integrate: (1) the plurality of reports from others tied to individual(s) of interest; and (2) structural features of the network generated from those ties. Network data was generated from digitally extracted cell-phone contact lists of a purposeful sample of 241 high-risk men in India. These data were integrated with interview responses to describe the corresponding individuals in the contact lists and the ties between them. HIV serostatus was collected for each respondent and served as an internal validation of the model's predictions of sex behavior. RESULTS: We found that network-based model predictions of sex behavior and self-reported sex behavior had limited correlation (54% agreement). Additionally, when respondent sex behaviors were re-classified to network model predictions from self-reported data, there was a 30.7% decrease in HIV seroprevalence among groups of men with lower risk behavior, which is consistent with HIV transmission biology. CONCLUSION: Combining the relative completeness and objectivity of digital network data with the substantive details of classical interview and HIV biomarker data permitted new analyses and insights into the accuracy of self-reported sex behavior.