Veterans Health Administration: Implementation of pharmacogenomic clinical decision support with statin medications and the SLCO1B1 gene as an exemplar.

PURPOSE: To describe the implementation of clinical decision support tools for alerting prescribers of actionable drug-gene interactions in the Veterans Health Administration (VHA). SUMMARY: Drug-gene interactions have been the focus of clinicians for years. Interactions between SCLO1B1 genotype and statin medications are of particular interest as these can inform risk for statin-associated muscle symptoms (SAMS). VHA identified approximately 500,000 new users of statin medications prescribed in VHA in fiscal year 2021, some of whom could benefit from pharmacogenomic testing for the SCLO1B1 gene. In 2019, VHA implemented the Pharmacogenomic Testing for Veterans (PHASER) program to offer panel-based, preemptive pharmacogenomic testing and interpretation. The PHASER panel includes SLCO1B1, and VHA utilized Clinical Pharmacogenomics Implementation Consortium statin guidelines to build its clinical decision support tools. The program's overarching goal is to reduce the risk of adverse drug reactions such as SAMS and improve medication efficacy by alerting practitioners of actionable drug-gene interactions. We describe the development and implementation of decision support for the SLCO1B1 gene as an example of the approach being used for the nearly 40 drug-gene interactions screened for by the panel. CONCLUSION: The VHA PHASER program identifies and addresses drug-gene interactions as an application of precision medicine to reduce veterans' risks for adverse events. The PHASER program's implementation of statin pharmacogenomics utilizes a patient's SCLO1B1 phenotype to alert providers of the risk for SAMS with the statin being prescribed and how to lower that risk through a lower dose or alternative statin selection. The PHASER program may help reduce the number of veterans who experience SAMS and may improve their adherence to statin medications.

Cognitive impairment and behavioural emergencies within the acute hospital setting.

BACKGROUND: Patients with cognitive impairment exhibiting agitation and aggression are challenging to manage in the acute hospital setting. When a patient's behaviours place themselves or others at risk of harm, a Clinical Aggression Response Team (C-ART) is dispatched.The aims of this project were to describe the characteristics of patients receiving a C-ART call and the experiences of C-ART staff members via semistructured interviews. Additionally, to audit local practice against two established standards of practice (Local C-ART Call Guideline and Australian Cognitive Impairment Guideline), to develop interventions to address identified shortfalls in adherence to these standards of practice and finally to re-evaluate adherence postintervention. METHODS: A retrospective pre and postintervention audit using qualitative (interview) and quantitative (file review) mixed method research approach was used. Interventions targeted doctor hospital orientation sessions, distribution of hospital guidelines including a new pharmacological sedation guideline and finally ward-based brief education sessions. RESULTS: Themes identified postintervention included improved familiarity with C-ART terminology, better understanding of C-ART member roles and improved communication among medical teams. However, there was continued pressure to use pharmacological sedation, a lack of debriefing and poor patient handover.File review of patients postintervention showed improvement from 36.8% to 65.6% in recording a provisional diagnosis and differentials for a patient behaviour necessitating a C-ART call. Additionally, the use of psychotropics during C-ART calls was lowered by 3.3% but did not reach significance (p=0.62). CONCLUSION: Behavioural disturbances in the elderly present many challenges for health staff. Interactive orientation sessions for doctors and distribution of hospital guidelines were shown to improve compliance with Local C-ART Call and Australian Cognitive Impairment Guidelines. Patients who receive multiple C-ART calls require further exploration and consideration, as this subset of the patient population present unique challenges.

Review of the utility of routine mortality reviews among deaths on General Internal Medicine wards in a Canadian tertiary care hospital.

BACKGROUND: Hospital morbidity and mortality reviews are common quality assurance activities, intended to uncover latent or unrecognised systemic issues that contribute to preventable adverse events and patient harm. Mortality reviews may be routinely mandated by hospital policy or for accreditation purposes. However, patients under the care of certain specialties, such as general internal medicine (GIM), are affected by a substantial burden of chronic disease, advanced age, frailty or limited life expectancy. Many of their deaths could be viewed as reasonably foreseeable, and unrelated to poor-quality care. METHODS: We sought to determine how frequently postmortem chart reviews for hospitalised GIM patients at our tertiary care centre in Canada would uncover patient safety or quality of care issues that directly led to these patients' deaths. We reviewed the charts of all patients who died while admitted to the GIM admitting service over a 12-month time period between 1 July 2020 and 30 June 2021. RESULTS: We found that in only 2% of cases was a clinical adverse event detected that directly contributed to a poor or unexpected outcome for the patient, and of those cases, more than half were related to unfortunate nosocomial transmission of COVID-19 infection. CONCLUSION: Due to an overall low yield, we discourage routine mortality chart reviews for general medical patients, and instead suggest that organisations focus on strategies to recognise and capture safety incidents that may not necessarily result in death.

Mania Induced by Epidural Steroid Injection in an Elderly Female With No Psychiatric History.

The psychiatric risks of epidural steroid injections for chronic pain in a geriatric patient with no prior psychiatric history are presented here. A 76-year old Caucasian female presented to the emergency department with her family for an inability to sleep, confusion, and behavioral outbursts. The mood instability and psychosis were reported as having started a week after her third epidural steroid injection for low-back pain associated with a prior fall. After 12 days of mixed treatment outcomes and increasing paranoia without any localized neurological findings, the patient was transferred to the geriatric psychiatry unit. Upon admission to the inpatient unit, she was loud, grandiose, verbally aggressive, unable to sleep, hyper-religious, paranoid, and identified her husband and daughter as demons. The patient was started on risperidone and valproic acid for the management of psychosis and manic symptoms. Hyper-religiosity and paranoia greatly improved within a week, though the patient remained very talkative and tangential, with a disorganized thought process. Valproic acid was titrated to 500 mg twice a day, yielding a level of 56.2 ug/ml, accompanied by improvement to mild talkativeness and circumstantiality. She was able to interact appropriately, with minimal lorazepam requirement, and discharged with a linear thought process and absence of psychosis. On outpatient follow up, there were minimal residual mania and no recurrence of psychosis, allowing her to be weaned off valproic acid and to discontinue risperidone. Two months later, symptoms resolved completely. The persistence of this patient's psychosis for nearly one month, and mania for about three months, underscores the importance of careful risk-benefit analysis before initiating epidural steroids. This is particularly important in elderly patients who may be more susceptible to psychiatric adverse effects that can outlast any analgesic benefits.

Attempted Suicides in the Elderly With Existing DNRs: An Emerging Geriatric Ethical Dilemma.

Several critical clinical and ethical issues, including immediate treatment decisions, emerged in a case of a double suicide attempt by an elderly couple with a suicide pact and existing do-not-resuscitate (DNR) documentation. This case was complicated by the advanced age of both patients and their family's expectations and perception of mental illness in the geriatric population. In addition to the myriad of legal and ethical challenges that frequent the end-of-life care, the emerging trend of suicide pacts among the elderly, particularly with existing DNR documentation, warrants further exploration.

Unmasked Testicular Seminoma During Use of Hormonal Transgender Woman Therapy: A Hidden hCG-Secreting Tumor.

Management of gender-affirming hormone therapy (HT) in transgender women includes surveillance of testosterone (T) levels. Failure of T to suppress, despite adherence to therapy, warrants additional investigations for unexpected sources of T or factors stimulating T secretion. Possible causes include T or gonadotropin production by an occult neoplasm. Testicular cancer is the most common malignancy affecting biological men aged between 15 and 35 years. Patients may be asymptomatic until tumor burden is high and/or metastatic. Hormone-producing tumors have rarely been reported in treated transgender women. Routine screening tests are recommended in a gender-incongruent person as per the 2017 Endocrine Society guidelines with measurement of T levels every 3 months initially to reach a goal of less than 50 ng/dL. Expectations should be discussed in detail with the transgender person since anticipated physical changes may not be notable for 6 to 18 months. We herein describe a case of a transgender woman who underwent standard HT including gonadotropin suppression with a gonadotropin-releasing hormone agonist, whose total T level failed to suppress. Testing revealed an elevated serum level of the beta subunit of human chorionic gonadotropin (ß-hCG), diagnostic of an hCG-secreting testicular seminoma, as the underlying cause of unexpected T production. This case illustrates how easily a testicular cancer can remain unnoticed because it can be asymptomatic and the necessity to be alert to, and act on, anomalous laboratory results during treatment of a transgender person.

Impact of a Hospital Community Based Palliative Care Partnership: Continuum from Hospital to Home.

Objectives: To discuss the outcomes of a formalized care transition process for palliative care patients from the hospital to the community. Background: Patients who received inpatient palliative care services from the specialist palliative care team in the hospital or who were identified as needing community palliative care services have inadequate support on discharge. Methods: A retrospective review of the medical records of patients admitted to the community based palliative care (CBPC) program, Arizona Palliative Home Care (AZPHC) over a 12-month period (June 2018 to May 2019) was undertaken with a focus on the frequency and pattern of hospital events pre- and postadmission to the program. Patient/family satisfaction data obtained from telephone surveys were evaluated. The medical records from patients (n = 294) with advanced complex illnesses who were admitted to AZPHC from the five Honor Health Network hospitals were included in this study. Results: Of the 294 patients' records reviewed, 80% were in the 65 and older age group and had a mean length of stay on AZPHC of ∼40 days. Comparing acute care utilization pre and post AZPHC admission, there was a reduction of 68.95% at 60 days and 68.22% at 90 days. In addition, 128 avoided hospital events were recorded, and 86% of patients were very likely to recommend AZPHC to family or friends. Discussion: Collaboration between a hospital palliative care team and a CBPC program resulted in high quality transitions across care settings and reduction in acute care utilization.

Review of the veteran affairs diabetes trial: Lessons learned.

Despite robust evidence linking long-term hyperglycemia with cardiovascular complications, several large randomized trials found only modest benefits from intensive compared to standard glucose control. Of these trials, the Veteran Affairs Diabetes Trial (VADT), offers a unique long-term perspective in that there were analyses of outcomes at the end of the intervention trial, 5-years post-trial, and after 10-years post-trial. From the VADT and other large trials, we draw several valuable lessons that are relevant to the care of patients with type 2 diabetes. Intensive glucose control reduces development of nephropathy and retinopathy but not neuropathy, though evaluations of neuropathy are less consistent and conclusions regarding outcomes less reliable. While the VADT did not demonstrate reduction in cardiovascular outcomes at completion of the glucose lowering intervention, it did demonstrate a 17% reduction 5-years post-trial, which waned by 10-years post-trial observation. Of interest, the 5-year post trial period included 3 additional years of HbA1c separation between treatment groups which suggests that longer-term glucose control may be needed before benefits are seen. Other factors including hypoglycemia and increased glucose variation are also associated with cardiovascular events and are more prevalent during intensive glucose control, potentially lessening the benefit of lowering average glucose levels. Finally, intensive glucose control requires substantial effort from both the patient and clinician perspective. All of these factors must be kept in mind when considering the benefits of aggressive glucose control for each patient.

Toluene Toxicity: A Case Report of Transdermal Exposure Causing Hypokalemic Paralysis.

RATIONALE: Hypokalemia is a common finding. Typically asymptomatic presentations of neuromuscular weakness emerge at levels below 2.5 mmol/L. Causes include gastrointestinal losses, renal losses, or intracellular shift, with gastrointestinal losses and diuretics accounting for the majority. Although the cause is often apparent on clinical assessment, a systematic approach incorporating urine biochemistry can aid in narrowing the differential in obscure cases. PRESENTATION: We describe a case of a previously healthy 27-year-old man who presented with acute ascending paralysis, with an associated severe hypokalemia and metabolic acidosis. There were no apparent causes on clinical assessment. DIAGNOSIS: Based on analysis of urine biochemistry, we concluded that a pathologic kaluresis was present, and given his acidemia and transient pathology, we diagnosed the patient with hypokalemic paralysis secondary to toluene toxicity. INTERVENTIONS: We provided supportive care and electrolyte repletion for our patient; no specific therapies for toluene were required. Our patient was counseled regarding appropriate protective measures when handling toluene. OUTCOMES: Complete neurologic recovery and biochemical normalization occurred within 48 hours of presentation with supportive care. He continued to use proper precautions when handling toluene, and experienced no symptom relapse, or further abnormalities on both blood and urine chemistry. LESSONS LEARNED: Using this case, we review an algorithmic approach incorporating urine biochemistries to aid in the workup of hypokalemia. We review toluene as a toxicologic entity and highlight its role as a cause of hypokalemia.

JUSTIFICATION: L'hypokaliémie est fréquente et généralement asymptomatique. Les symptômes de faiblesse neuromusculaire se manifestent à des concentrations inférieures à 2,5 mmol/L. Les pertes de potassium au niveau gastro-intestinal ou rénal et les déplacements intracellulaires sont parmi les causes; les pertes gastro-intestinales et les diurétiques constituant les principales causes. Bien que l'étiologie soit souvent apparente à l'évaluation clinique, une approche systématique intégrant la biochimie de l'urine pourrait aider à réduire le diagnostic différentiel dans les cas plus incertains. PRÉSENTATION DU CAS: Nous discutons du cas d'un homme de 27 ans précédemment en bonne santé qui présentait une paralysie ascendante aigüe associée à une grave hypokaliémie et à une acidose métabolique. Aucune étiologie n'était apparente lors de l'évaluation clinique. DIAGNOSTIC: L'analyse biochimique de l'urine a permis de confirmer la présence d'une kaliurèse pathologique et, compte tenu de l'acidémie et de la pathologie transitoire, de diagnostiquer une paralysie hypokaliémique consécutive à une intoxication au toluène. INTERVENTIONS: Le patient a reçu le traitement médical et la supplémentation en électrolytes appropriés. Aucun traitement spécifique pour le toluène n'était nécessaire. Le patient a été informé des mesures de protection adéquates à prendre pour la manipulation du toluène. RÉSULTATS: Une récupération neurologique complète et une normalisation biochimique ont été constatées dans les 48 heures suivant le début du traitement. Le patient a pris les mesures de protection appropriées lors de la manipulation du toluène et n'a éprouvé aucun symptôme de rechute ou anomalie biochimique du sang ou de l'urine depuis. ENSEIGNEMENTS TIRÉS: Avec ce cas, nous avons analysé une approche algorithmique intégrant la biochimie urinaire pour faciliter le diagnostic de l'hypokaliémie. Nous avons également examiné le toluène en tant qu'agent toxique et souligné son rôle comme étiologie de l'hypokaliémie.

Current practices, barriers and enablers for advance care planning among healthcare workers of aged care facilities in western New South Wales, Australia.

INTRODUCTION: Advance care planning (ACP) and advance care directives (ACDs) play a vital role in preparing for end-of-life care. However, current literature suggests that uptake of ACP and ACDs in rural Australia is low, which may contribute to lower quality care for the older rural population, as patients' end-of-life wishes may not be recognised and acknowledged. This study aims to provide a current perspective on the attitudes and practices of healthcare workers from residential aged care facilities towards ACP and ACDs in the central west, far west and Orana regions of New South Wales, Australia. METHODS: This was a mixed-methods study incorporating anonymous survey and individual interviews. Healthcare workers from 12 residential aged care facilities within the studied region completed surveys (n=109). The 40-item survey assessed participant demographics, training and experience with ACP and ACD, attitudes towards ACP and ACDs, and barriers and facilitators towards the use of ACP and ACDs in their organisation. Five participants were interviewed to explore these issues in more depth. RESULTS: Almost three-quarters (71%) of respondents thought that ACP is necessary while almost half (48%) were involved with >5 ACDs in the past 12 months. Formal training was seen as beneficial by most (81%) but the importance of practical experience was also acknowledged. No statistically significant differences were found in attitudes between those with 5 years of experience. Avoidance of unnecessary resuscitation was a consistent theme in all interviews and the potential of a nurse-led model of delivery was identified. Patient factors such as decreased capacity to make informed decisions were identified as barriers that could be circumvented by pre-emptive implementation of ACP discussion. The rural setting was identified as a facilitator due to a supportive community, which helped to mitigate barriers such as limited staffing. CONCLUSIONS: Attitudes towards ACP in rural New South Wales are highly positive. The rural setting is a facilitator to ACP, and ACDs are approached in a multidisciplinary fashion. Further training is an identified need although on-the-ground experience may be more beneficial.

Overview of Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Patients with Type 2 Diabetes.

BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes. DISCUSSION: This article reviews the evidence from phase 3 clinical trials for each of the 5 GLP-1 receptor agonists by comparing them against one another and with other existing therapies, including metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas. Incretin-based therapies have emerged as attractive agents for the treatment of type 2 diabetes. They target the GLP-1 hormone, which is partly responsible for insulin release and for attenuating hyperglycemia during meals (ie, the incretin effect). The 2 classes of incretin-based therapy currently available are GLP-1 receptor agonists and DPP-4 inhibitors, which prevent the breakdown of GLP-1. Both classes are attractive options, given their glucose-lowering effects without the adverse effects of hypoglycemia and weight gain. The different mechanisms of action of these therapies result in generally greater efficacy with GLP-1 receptor agonists, albeit at the expense of slightly increased gastrointestinal symptoms. These agents exert their effects by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying, thereby reducing appetite. Currently, 5 GLP-1 receptor agonists are available, including exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide; semaglutide may soon become available as the newest agent. With the exception of the investigational oral semaglutide, which has shown promising results, the other 5 agents are administered as subcutaneous injections, at different dosing intervals. CONCLUSION: Currently, 5 GLP-1 receptor agonists are available for use in the United States. Although they are all in the same drug class, some significant differences exist among the various GLP-1 receptor agonists. The choice of a specific GLP-1 receptor agonist will depend on the patient preferences, potential adverse effects, and cost.

Evaluating Student Attitudes: Perceptions of Interprofessional Experiences Following Participation in a Student-Run Free Clinic.

It is increasingly evident that patient health outcomes are improved when they are treated by an effective interdisciplinary healthcare team. Many also endorse that learning to function collaboratively in interdisciplinary settings should start at the onset of one's medical education. Student-run free clinics, such as the University of Central Florida College of Medicine's (UCF COM) KNIGHTS (Keeping Neighbors In Good Health Through Service) Clinic, provide opportunities for students to work in concert with other healthcare professionals. This study aimed to discern whether volunteering in this setting had a positive impact on medical students' perception of working within an interdisciplinary team. A single survey was distributed via Qualtrics to all first and second-year medical students (N = 248) at the UCF COM. The items of interest examined in this study were part of a larger study described elsewhere. The mean responses on a 5-point Likert-like scale to these survey items were recorded and compared between two cohorts: KNIGHTS volunteers and non-volunteers. One hundred twenty-three (49.6%) students responded to the survey and most items showed no statistically significant difference between the two groups (p-value > 0.05). However, there were a few items of interest that did show a significant difference. These included KNIGHTS volunteers being much more likely to have worked with other healthcare professionals (p < 0.001) as well as believing themselves to have a better understanding of the role of medicine within an interprofessional team (p = 0.016). Additionally, KNIGHTS volunteers were more likely to feel like they understood the role of patient education (p = 0.031) and pharmacy (p = 0.040) within an interprofessional team. Interestingly, KNIGHTS volunteers were also more likely to believe that problem-solving skills should be learned with students within their own discipline (p = 0.009) as well as that there is little overlap between the roles of medical students and students from other healthcare disciplines (p = 0.044). Still, overall results showed that both volunteers and non-volunteers had an overall positive perception of interdisciplinary teams and working with other healthcare professionals.

The Effect of Volunteering at a Student-Run Free Healthcare Clinic on Medical Students' Self-Efficacy, Comfortableness, Attitude, and Interest in Working with the Underserved Population and Interest in Primary Care.

INTRODUCTION: The number of primary care physicians in the United States continues to lag behind the number of uninsured people. There has been a growing demand for medical students to improve their self-efficacy, comfortableness, attitude, and interest in working with the underserved and in primary care. This study aims to discern whether volunteering at a student-run, free healthcare clinic has a positive impact on these five variables of interest or not. METHODS: A 95-item survey was distributed through Qualtrics Survey Software (Qualtrics, Provo, UT, USA) to medical students from the Class of 2018 and Class of 2019 at the University of Central Florida College of Medicine. They were recruited via emails, Facebook, and in-classroom announcements. Mean responses on a Likert-like scale to different survey items were collected and compared between two study cohorts: Keeping Neighbors In Good Health Through Service (KNIGHTS) Clinic volunteers and non-volunteers. RESULTS: Results from 128 students showed no significant differences in the means between the two cohorts (p-values were not significant). When volunteers were asked the survey item, "KNIGHTS Clinic positively influenced my attitude towards working with underserved patients," 62% strongly agreed, 26% agreed, 10% were neutral, and 2% disagreed. DISCUSSION: Based on the results, volunteering at KNIGHTS Clinic may not have a positive impact on the five variables of interest. However, the lack of significance may also be due to certain limitations of this study addressed elsewhere in this paper. With the majority of KNIGHTS Clinic volunteers agreeing that "KNIGHTS Clinic positively influenced […their] attitude towards working with underserved patients," there may be a positive impact of volunteering on volunteers' attitude towards working with the underserved.

The Metalloprotease Neprilysin Degrades and Inactivates Apelin Peptides.

The apelinergic system is a mammalian peptide hormone network with key physiological roles. Apelin isoforms and analogues are believed to be promising therapeutics for cardiovascular disease. Despite extensive studies on apelin-13 degradation patterns, only one protease, angiotensin-converting enzyme 2 (ACE2), had been implicated in its physiological regulation. Through use of a peptide-based fluorescent probe, we identified the metalloprotease neprilysin (NEP, a target for Entresto used in treatment of heart failure) as an enzyme that cleaves apelin isoforms. In vitro NEP proteolysis generated fragments that lacked the ability to bind to the apelin receptor, thereby making NEP the first protease to fully inactivate apelin. The involvement of NEP in the apelinergic system contributes to the understanding of its role in cardiovascular physiology.

Hypofractionated versus conventionally fractionated radiotherapy for ductal carcinoma in situ (DCIS) of the breast.

INTRODUCTION: Hypofractionated radiotherapy (RT) in the setting of early invasive breast cancer has been shown to have similar local control rates and cosmetic outcomes as conventionally fractionated RT. This study compares ipsilateral recurrence rates between hypofractionated and conventional RT, with and without a boost. The effect of hypofractionated RT and chest wall separation (CWS) on cosmetic outcome was also assessed. METHODS: All patients with ductal carcinoma in situ (DCIS) treated between 1998 and 2012 across two sites of a single cancer institution were retrospectively studied. Patients were analysed according to those receiving conventional RT (≤2 Gy per fraction) and those receiving hypofractionated RT (>2 Gy per fraction), as well as the presence or absence of a tumour bed boost. Data were collected through electronic medical records and local cancer registry. Cosmetic outcome was scored by physicians on a four-point scale during clinical follow-up appointments. RESULTS: One hundred and ninety-seven patients were treated for DCIS during the study period. One hundred and forty-one were treated with conventional RT, and 56 with hypofractionated RT. After a median follow up of 4.4 years, there were 12 ipsilateral recurrences, of which seven were invasive disease and five DCIS. Ten recurrences occurred in patients who received conventional RT (7.1% recurrence rate) and two in those who received hypofractionated RT (3.6% recurrence rate) (P = 0.48). Cosmetic outcomes were not significantly different between conventional and hypofractionated RT (P = 0.06). CONCLUSIONS: Hypofractionation represents a suitable alternative for treating DCIS in the absence of randomised data.

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity.

The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.