No abstract

Previous studies have shown that brief access to cocaine yields an increase in D2 receptor binding in the medial prefrontal cortex (mPFC), but that extended access to cocaine results in normalized binding of D2 receptors (i.e. the D2 binding returned to control levels). Extended access conditions have also been shown to produce increased expression of the NR2 subunit of the NMDA receptor in the mPFC. These results implicate disrupted glutamate and dopamine function within this area. Therefore, in the present study, we monitored glutamate and dopamine content within the mPFC during, or 24 hrs after, cocaine self-administration, in animals that experienced various amounts of exposure to the drug. Naïve subjects showed decreased glutamate, and increased dopamine, levels within the mPFC during cocaine self-administration. Exposure to 7 lhr daily cocaine self-administration sessions did not alter the response to self-administered cocaine, but resulted in decreased basal dopamine levels. While exposure to 17 lhr sessions also resulted in reduced basal dopamine levels, these animals showed increased dopaminergic, but completely diminished glutamatergic, response to self-administered cocaine. Finally, exposure to 17 cocaine self-administration sessions, the last ten of which being 6h sessions, resulted in diminished glutamatergic response to self-administered cocaine and reduced basal glutamate levels within the mPFC, while normalizing (i.e. causing a return to control levels) both the dopaminergic response to self-administered cocaine as well as basal dopamine levels within this area. These data demonstrate directly that the transition to escalated cocaine use involves progressive changes in dopamine and glutamate function within the mPFC.

Context: Little is known about the hopes patients with advanced (incurable) cancer have for their treatment. Objectives: To describe the treatment hopes of advanced cancer patients, factors associated with expressing specific hopes, and the persons with whom hopes are discussed. Methods: We surveyed 265 advanced cancer patients in the USA about their hopes for treatment at baseline and after three months. We developed a taxonomy of hopes for treatment, which two investigators used to independently code patient responses. We explored associations between hopes for cure and patient covariates. Results: We developed 8 categories of hopes. We were able to apply these codes reliably, and 95% of the patient’s responses fit at least one hope category. The hope categories in order of descending baseline prevalence were: quality of life, life extension, tumor stabilization, remission, milestone, unqualified cure, control not otherwise specified (NOS), and cure tempered by realism. Most patients reported discussing hopes with partners, family/friends, and oncologists; a minority reported discussing hopes with nurses, primary care physicians (PCPs), clergy, or support groups. In logistic regression analysis, unqualified hopes for cure were more likely in younger patients and in those who did not endorse discussing their hopes with primary care physicians. Conclusion: Advanced cancer patients harbor a range of treatment hopes. These hopes often are not discussed with key members of the healthcare team. Younger age and lack of discussion of hopes with PCPs may lead to less realistic hopes for cure.

Background The epidemiology of mental health disorders has important theoretical and practical implications for health care service and planning. The recent increase in big data storage and subsequent development of analytical tools suggest that mining search databases may yield important trends on mental health, which can be used to support existing population health studies. Objective This study aimed to map depression search intent in the United States based on internet-based mental health queries. Methods Weekly data on mental health searches were extracted from Google Trends for an 11-year period (2010-2021) and separated by US state for the following terms: “feeling sad,” “depressed,” “depression,” “empty,” “insomnia,” “fatigue,” “guilty,” “feeling guilty,” and “suicide.” Multivariable regression models were created based on geographic and environmental factors and normalized to the following control terms: “sports,” “news,” “google,” “youtube,” “facebook,” and “netflix.” Heat maps of population depression were generated based on search intent. Results Depression search intent grew 67% from January 2010 to March 2021. Depression search intent showed significant seasonal patterns with peak intensity during winter (adjusted P<.001) and early spring months (adjusted P<.001), relative to summer months. Geographic location correlated with depression search intent with states in the Northeast (adjusted P=.01) having higher search intent than states in the South. Conclusions The trends extrapolated from Google Trends successfully correlate with known risk factors for depression, such as seasonality and increasing latitude. These findings suggest that Google Trends may be a valid novel epidemiological tool to map depression prevalence in the United States.

Alcohol use disorder is a constellation of symptoms and behaviours related to dependence and abuse. It is present in 11.0% of US adults and is a leading cause of death and healthcare expenditures in the USA. Medication-assisted treatment (MAT) is medication to reduce cravings, decrease rewards or limit withdrawal symptoms in combination with behavioural therapy.A review of all patients with an alcohol-related condition admitted to internal medicine teams at an academic medical centre over a 7-month period (N=583) identified that only 1.4% (n=8) were discharged with an MAT prescription. Quality improvement methods were used to increase the proportion of patients discharged with an MAT prescription.Implementing educational interventions and embedding a recommendation for MAT into the order sets used to treat alcohol withdrawal increased the percentage of patients with an alcohol-related condition that were discharged with an MAT prescription to 11.2%.MAT remains an underused intervention for the treatment of alcohol use disorder. However, combining educational and structural interventions, including just-in-time teaching, can successfully increase the percentage of patients who receive an MAT prescription.