Outcomes from the Northeast England cohort of autosomal dominant polycystic kidney disease (ADPKD) patients on tolvaptan.

Autosomal dominant polycystic kidney disease (ADPKD) is a cause of end-stage kidney disease (ESKD). The vasopressin V2-receptor antagonist tolvaptan has been shown within randomized clinical trials to slow down decline of kidney function in patients with ADPKD at risk of rapid progression. We performed a retrospective review of a Northeast England cohort of adult ADPKD patients who had been established on tolvaptan therapy to determine its efficacy in a real-world clinic setting.

Evaluation of off-label rapamycin use to promote healthspan in 333 adults.

Rapamycin (sirolimus) is an FDA-approved drug with immune-modulating and growth-inhibitory properties. Preclinical studies have shown that rapamycin extends lifespan and healthspan metrics in yeast, invertebrates, and rodents. Several physicians are now prescribing rapamycin off-label as a preventative therapy to maintain healthspan.

Glutamine and GABA alterations in cingulate cortex may underlie alcohol drinking in a rat model of co-occurring alcohol use disorder and schizophrenia: an 1H-MRS study.

Alcohol use disorder commonly occurs in patients with schizophrenia and significantly worsens the clinical course of the disorder. The neurobiological underpinnings of alcohol drinking are not well understood. Magnetic resonance spectroscopy (MRS) has been used to assess the neurochemical substrates that may be associated with alcohol drinking in patients; however, the causal impact of these findings remains elusive, highlighting the need for studies in animal models.

Designing and evaluating an interprofessional education conference approach to antimicrobial education.

Background: Arguably, Medical School curricula are deficient in learning opportunities related to the safe and effective use of medicines, in particular antimicrobials. Infection management is complex and multidisciplinary, and learning opportunities should reflect these principles. Aligned to the complexity of the subject matter, simulation and interprofessional based teaching are methods that can foster the collaborative skills required of future healthcare professionals.

Building capacity for collaborative research on opioid and other substance use disorders through the Clinical and Translational Science Award Program.

The opioid crisis in the USA requires immediate action through clinical and translational research. Already built network infrastructure through funding by the National Institute on Drug Abuse (NIDA) and National Center for Advancing Translational Sciences (NCATS) provides a major advantage to implement opioid-focused research which together could address this crisis. NIDA supports training grants and clinical trial networks; NCATS funds the Clinical and Translational Science Award (CTSA) Program with over 50 NCATS academic research hubs for regional clinical and translational research.

Olanzapine Plus Samidorphan (ALKS 3831) in Schizophrenia and Comorbid Alcohol Use Disorder: A Phase 2, Randomized Clinical Trial.

Objective: Alcohol use disorder (AUD) is a common comorbidity of schizophrenia. No effective pharmacologic treatment is available for both disorders to date.

Methods: In a phase 2, double-blind study, patients with schizophrenia and AUD experiencing ≥ 10 drinking and ≥ 2 heavy-drinking days in the previous month and recent (≤ 6 mo) disease symptom exacerbation were recruited between June 2014 and March 2017.

Alcohol Use Disorder and Schizophrenia or Schizoaffective Disorder.

Schizophrenia and schizoaffective disorder are schizophrenia spectrum disorders that cause significant disability. Among individuals who have schizophrenia or schizoaffective disorder, alcohol use disorder (AUD) is common, and it contributes to worse outcomes than for those who do not have co-occurring substance use disorder. Common neurobiological mechanisms, including dysfunction in brain reward circuitry, may explain the high rates of co-occurrence of schizophrenia and AUD or other substance use disorders.

Sex differences in the ability of corticostriatal oscillations to predict rodent alcohol consumption.

Background: Although male and female rats differ in their patterns of alcohol use, little is known regarding the neural circuit activity that underlies these differences in behavior. The current study used a machine learning approach to characterize sex differences in local field potential (LFP) oscillations that may relate to sex differences in alcohol-drinking behavior.

Methods: LFP oscillations were recorded from the nucleus accumbens shell and the rodent medial prefrontal cortex of adult male and female Sprague-Dawley rats.

Corticostriatal Oscillations Predict High vs. Low Drinkers in a Rat Model of Limited Access Alcohol Consumption.

Individuals differ in their vulnerability to develop alcohol dependence, which is determined by innate and environmental factors. The corticostriatal circuit is heavily involved in the development of alcohol dependence and may contain neural information regarding vulnerability to drink excessively. In the current experiment, we hypothesized that we could characterize high and low alcohol-drinking rats (HD and LD, respectively) based on corticostriatal oscillations and that these subgroups would differentially respond to corticostriatal brain stimulation.

Finding the balance between model complexity and performance: Using ventral striatal oscillations to classify feeding behavior in rats.

The ventral striatum (VS) is a central node within a distributed network that controls appetitive behavior, and neuromodulation of the VS has demonstrated therapeutic potential for appetitive disorders. Local field potential (LFP) oscillations recorded from deep brain stimulation (DBS) electrodes within the VS are a pragmatic source of neural systems-level information about appetitive behavior that could be used in responsive neuromodulation systems. Here, we recorded LFPs from the bilateral nucleus accumbens core and shell (subregions of the VS) during limited access to palatable food across varying conditions of hunger and food palatability in male rats.

Potent Dopamine D2 Antagonists Block the Reward-Enhancing Effects of Nicotine in Smokers With Schizophrenia.

Antipsychotics that are potent dopamine (DA) D2 receptor antagonists have been linked to elevated levels of nicotine dependence in smokers with schizophrenia. Because activation of D2 receptors mediates motivation for nicotine, we examined whether potent D2 antagonists would diminish nicotine's ability to stimulate reward processing-a mechanism that may drive compensatory increases in smoking. Smokers with schizophrenia (n = 184) were recruited and stratified into medication groups based on D2 receptor antagonist potency.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

Background: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD).

Methods: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.

Machine Learning Based Classification of Deep Brain Stimulation Outcomes in a Rat Model of Binge Eating Using Ventral Striatal Oscillations.

Neuromodulation-based interventions continue to be evaluated across an array of appetitive disorders but broader implementation of these approaches remains limited due to variable treatment outcomes. We hypothesize that individual variation in treatment outcomes may be linked to differences in the networks underlying these disorders. Here, Sprague-Dawley rats received deep brain stimulation separately within each nucleus accumbens (NAc) sub-region (core and shell) using a within-animal crossover design in a rat model of binge eating.

Making it work: the feasibility and logistics of delivering large-scale interprofessional education to undergraduate healthcare students in a conference format.

An interprofessional education conference was developed and delivered to undergraduate medical and pharmacy students to address training needs around appropriate antimicrobial prescribing, identification and management of sepsis, patient safety and interprofessional working. The day consisted of keynote lectures delivered by specialist speakers and three small group interprofessional teaching sessions exploring (1) the choice and prescribing of antimicrobials for a range of infections, (2) the diagnosis and management of sepsis utilising simulation methodology and (3) the discussion of a clinical error using significant event analysis. Students' attitudes and acceptance towards this educational intervention were assessed using a mixed methods evaluation.

Unique Effects of Clozapine: A Pharmacological Perspective.

Schizophrenia is a heterogenous and severe neuropsychiatric disorder that affects nearly 1% of the population worldwide. Antipsychotic drugs are the mainstay of treatment, but not all patients with schizophrenia respond to treatment with these agents. Clozapine, the first atypical antipsychotic, is a highly effective medication for patients with schizophrenia who do not respond to other antipsychotics.

Applying novel technologies and methods to inform the ontology of self-regulation.

Self-regulation is a broad construct representing the general ability to recruit cognitive, motivational and emotional resources to achieve long-term goals. This construct has been implicated in a host of health-risk behaviors, and is a promising target for fostering beneficial behavior change. Despite its clear importance, the behavioral, psychological and neural components of self-regulation remain poorly understood, which contributes to theoretical inconsistencies and hinders maximally effective intervention development.

Understanding marijuana's effects on functional connectivity of the default mode network in patients with schizophrenia and co-occurring cannabis use disorder: A pilot investigation.

Nearly half of patients with schizophrenia (SCZ) have co-occurring cannabis use disorder (CUD), which has been associated with decreased treatment efficacy, increased risk of psychotic relapse, and poor global functioning. While reports on the effects of cannabis on cognitive performance in patients with SCZ have been mixed, study of brain networks related to executive function may clarify the relationship between cannabis use and cognition in these dual-diagnosis patients. In the present pilot study, patients with SCZ and CUD (n=12) and healthy controls (n=12) completed two functional magnetic resonance imaging (fMRI) resting scans.