A Genetically Modified Skin Graft for Treating Alcohol Use Disorder and/or Polysubstance Abuse With Cocaine

Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We have developed and used a skin stem cell-based gene delivery platform and found that production of the glucagon-like peptide-1 (GLP1) from the grafted genetically modified skin reduced development and reinstatement of alcohol-induced drug-taking and seeking, voluntary oral alcohol consumption and alcohol-induced increase in dopamine (DA) levels in the nucleus accumbens (NAc). Moreover, we have developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Skin grafts-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by concurrent alcohol and cocaine injections. These results imply that gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.

A Rare Case of Botulism in an Adult Patient

Presentation of botulism in adults is extremely rare and symptoms can be easily confused for symptoms of acute stroke, Guillain-Barre, or myasthenia gravis. The purpose of this clinical case report is to ensure adult botulism will be included in the differential diagnoses for a patient with this presentation so swift and accurate care can be provided to ensure optimal patient outcome. A 41-year-old-female presented with complaints of sudden onset of difficulty speaking. The patient reports a history of intravenous polysubstance abuse and symptoms progressed to bilateral facial weakness, ptosis, and external ophthalmoplegia. With no notable findings from a non-contrast computed tomography and magnetic resonance imaging and given the symptoms, a diagnosis of wound botulism from intravenous drug use was made. Botulism antitoxin was given and the patient was admitted into the intensive care unit for supportive follow-up care. A colony of Clostridium species was discovered in this patient’s arm and the patient showed significant improvement after a few days of care.

Prescription Stimulant Misuse and Abuse: Characterization of Exposures Managed by United States (US) Poison Centers

The National Poison Data System (NPDS), is the data warehouse for the 55 US regional poison centers. While the primary role of a poison center is to provide medical management to the public and healthcare providers, a standardized database is used to collect case data. These data are routinely used to evaluate drug safety, including characterization of prescription medication misuse and abuse. While an effective therapy for attention deficit/hyperactivity disorder (ADHD), prescription stimulant medications (RxStim) may be misused and abused, a behavior that has been noted as an emerging public health concern particularly in relation to polysubstance abuse. The objective of this study was to characterize intentional exposures to RxStim in patients age >12 y of age as managed by US poison centers from Jan 2015- 31 Dec 2019.NPDS cases of intentional exposure to a RxStim in a patient >12 y managed from Jan 2015-Dec 2019 were included for analysis. Intentional exposures are defined in the NPDS manual as exposures that involve a purposeful action. These include intentional misuse, intentional abuse and intentional unknown cases. Intentional suspected suicide cases were excluded.A total of 12,972 cases met inclusion criteria, of which 62.5% involved a male patient. Most patients were aged 13–19 y (34.7%) or 20–39 y (50.5%). Over one-half (53.3%) of cases were intentional abuse, 29.1% intentional misuse, and 17.6% intentional unknown. While most exposures were via oral route of administration (90.7%), 9.5% were via inhalation/intranasal and 2.4% via injection (multiple routes may be reported). Other substances in addition to a RxStim were involved in 48.2% of cases, including benzodiazepines (11.2%), alcohol (8.8%), marijuana (5.1%), cocaine (3.7%), methamphetamine (3.0%) and atypical antipsychotics (2.5%). The majority of cases resulted in significant medical outcome (60.3%). This included 39.3% with a moderate effect (medical attention indicated, not life-threatening), 6.1% major effect (life-threatening), 1.0% death and 14.0% lost to follow-up but judged as a potentially toxic exposure. Another 22.4% reported minimally bothersome effects. Admission to a healthcare facility was reported for 1 out of 3 cases and another 36.3% were treated/evaluated/released from a healthcare service. An average of 2.3 clinical effects were reported per exposure, the most common being neurological effects (53.2%; examples include agitation, drowsiness/lethargy, confusion, hallucinations/delusions, tremor), cardiovascular effects (50.8%; examples include tachycardia, hypertension), and gastrointestinal effects (9.4%; examples include vomiting, nausea).RxStim misuse and abuse cases managed by US poison centers most often leads to significant medical outcomes which require medical attention. The role of these medications in polysubstance abuse is concerning and suggestive of needed strategies to address this increasingly important public health concern.Funding: Arbor Pharmaceuticals, LLC

Oral Valproate Sodium as an Alternative to Benzodiazepine in the Treatment of Catatonia- A Case Report

Alternative therapies are necessary to treat catatonia in patients with comorbidities that are not amenable to therapy with benzodiazepines or ECT. This is a patient with schizophrenia with catatonic features and a history of polysubstance abuse. Consequently, he was not a candidate for treatment with benzodiazepines, so an alternative needed to be found. GABAergic medications have been used previously as alternatives to benzodiazepines and ECT. In this case we chose sodium valproate, due to its cross-reaction with GABAergic systems. There are five reported cases using sodium valproate. Three of which were treated with intravenous valproate, while the remaining two do not specify the route of administration. We present a case where oral sodium valproate was used successfully for both acute and long-term catatonic treatment. To our knowledge, no other report has looked at both acute and long-term treatment with sodium valproate. Oral sodium valproate can be considered for patients with substance use disorders like COPD, sleep apnea or myasthenia gravis in which benzodiazepines are contraindicated and where ECT is not an option for treatment.

First Case Report of an Unusual Fungus (Sporopachydermia lactativora) Associated with a Pulmonary Infection in a Drug Injection User

In contrast to a robust literature on known pathogenic fungi such as Cryptococcus and Aspergillus species that cause pulmonary infections, reports of the uncommon genus Sporopachydermia causing infections are very limited. We present the first case report describing the fungus, Sporopachydermia lactativora as a likely cause of pneumonia in a patient with a history of polysubstance abuse and injection drug use (IDU). The patient recovered following antifungal treatment. The organism was recovered from a blood culture, 3 days post collection. Although CHROMagar was of little value, only yeast-like organisms were observed on cornmeal agar. The organism was not in the matrix-assisted laser desorption/ionization—time of flight (MALDI-TOF) mass spectrometry database. Definitive identification was achieved using the ribosomal DNA (rDNA) sequence analysis by targeting the ITS1 (internal transcribed spacer 1) region. This case report is intended to promote awareness of this fungus as a potential pathogen, by providing new information that has not yet been reported in the literature, and prompts physician awareness to suspect a fungal infection when managing patients with a history of IDU as a potential source of unique environmental organisms not previously encountered, warranting more comprehensive diagnosis and treatment options.

Pandemics 2020 –COVID 19 Silent Hypoxia and Polysubstance Use: A Unique Case Report

The coronavirus (COVID-19) pandemic continues to bring challenges in identification and management of which the “happy hypoxic” or silent hypoxia presentation has been found to present its own unique challenge. A 67-year-old African American COVID-19 positive female presents to the emergency department (ED) with a chief complaint of decreased oral intake and responsiveness, oriented and stable, with oxygen saturations found to drop as low as 47%. The patient was successfully managed with supplemental oxygen and determined to be a “happy hypoxic” with recent polysubstance abuse. Silent hypoxia or the “happy hypoxic” patient is another unique phenomenon associated with the variable presentations of COVID-19. Multiple etiologies and pathophysiologic explanations exist to explain this stable patient whom would otherwise be expected to require aggressive management with a poor prognosis. An alternative diagnosis should be explored for those silent hypoxic patients with symptoms.

Coexistence of Substance Abuse among Emergency Department Patients Presenting with Suicidal Ideation

Background. Patients who are suicidal commonly seek care in the emergency department (ED). Few studies have examined the coexistence between suicidal ideation, substance abuse, and psychiatric diagnosis. Objectives. This study sought to determine how often suicidal ED patients have coexisting substance abuse and psychiatric diagnosis in addition to describing the characteristics of target population. Methods. In this retrospective cohort study, chart reviews were conducted of patients over 12 with suicidal ideation who presented to an academic ED from October 2016 to March 2017. Data abstracted included gender, age, insurance, prior psychiatric diagnoses, substances abused, presence of a suicide attempt, prior suicidality, number of ED visits in the prior year, and disposition. Both descriptive and inferential statistics were calculated. Results. There were 427 patient visits to the ED for suicidality during the study period, of which 54% were male, with a mean age of 34 years. Most patients (92%) had a psychiatric diagnosis, most commonly depression (67%). More than one psychiatric diagnosis was reported in 51% of patients, while 8% had no reported underlying psychiatric diagnosis. Substance abuse was reported in 58% of patients, including marijuana (42%) and opioids (41%). Polysubstance abuse was reported in 42%. Approximately half of the patients had three or more ED visits in the previous 12 months. Most patients were insured by Medicaid (51%), while 59% were admitted for inpatient treatment. Conclusion. Substance abuse and psychiatric diagnosis were reported frequently among patients presenting to the ED with suicidal ideation, often involving more than one substance/diagnosis. Future studies should be aimed at evaluating the relationship between these conditions and determining how to better care for this population.

Nicotine and Opioid Polysubstance Abuse: Enhancement of opioid self-administration by systemic nicotine and modulation of opioid-associated memories by insular nicotine

Concurrent nicotine use is associated with increased liability for the development and exacerbation of opioid-use disorders. Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, & 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.