Intravenous Abuse Research Articles

Modernizing Endocarditis Treatment Through a Multidisciplinary Team Approach

Fostering a multidisciplinary team approach in cardiovascular care to manage valve disease and heart failure is not a new concept; however, it is underused in the setting of infective endocarditis (IE). IE is one of the deadliest medical conditions largely due to a delay in diagnosis and treatment as a result of the time used to individually coordinate care between multiple specialties. Research shows a multidisciplinary endocarditis team decreases mortality rates by decreasing the time between admission and initiating treatment. Patients with IE secondary to intravenous substance abuse pose complex challenges to developing an effective, comprehensive, multidisciplinary endocarditis team.

Reaching the limits of antipsychotic treatment: the upper end of severe schizophrenia in forensic institutions - a case report

IntroductionSevere schizophrenia is often closely related to delinquency resulting in relative overrepresentation of these manifestations of disease in forensic institutions.ObjectivesThe aim of the present work is to report the therapeutic challenges in a case of severe schizophrenia in a forensic institution from a clinical viewpoint as a basis for discussion.MethodsThe case report is based on the available clinical documentation, exploratory interviews as well as a structured clinical interview (PANSS).ResultsPresenting a case of a 41-year-old, male Caucasian inpatient suffering from a catatonic schizophrenia, we report the challenges in treatment of chronic, major schizophrenic disease resistant to antipsychotic medication. Without any previous criminal convictions, he has been instutionalized in a forensic psychiatry after a bodily harm to a random stranger about three years ago. Regarding medical history, information is limited to a few inpatient admissions prior to detention documenting intravenous opioid and cocaine abuse. Initially, the patient presented sexual disinhibition and ongoing endangerment of others with frequent assaults to other patients and prison guards. From a psychopathological viewpoint several phenomenona such as delusional intuition, acoustic, tactile and coenaesthetic hallucinations, echolalia, mannerisms and thought diffusions reflect the severe course of the disease (PANSS: P 34/49, N 38/49, G 73/112; total 145/210). Therapeutic attempts with an antipsychotic combination of risperidone, olanzapine and quetiapine as well as valproic acid resulted in insufficient recovery with persistent physical assaults and florid psychosis. In reaction to that zuclopenthixol for impulse control was added. As from the beginning of this year a switch of medication by gradually replacing risperidone and zuclopenthixol with haloperidol and clozapine showed modest success. Under the current medication and therapeutic drug levels the patient does not pose endangerment to others. However, regular tonic-eye fits require supplementary treatment with biperiden, and the patient still presents frequent periods of self-harm punching himself, verbal lack of impulse control and the psychopathological phenomenona described before. In addition to pharmacological treatment the patient receives psychotherapeutic one-on-one conversations. Despite approaching all limits of the available antipsychotic repertoire, psychopathology is only insufficiently controlled leading considerations to electroconvulsive therapy as a treatment of last resort.ConclusionsCertainly, the present case is exemplary for a severely ill population of patients reaching – after a long and untreated course of disease - a chronic stage that does not sufficiently respond to a multitude of treatment attempts despite proper compliance raising the urgent need for further treatment options.Disclosure of InterestNone Declared

In vitro test methods for evaluating high molecular weight polyethylene oxide polymer induced hemolytic and thrombotic potential

To combat opioid abuse, the U.S. Food and Drug Administration (FDA) released a comprehensive action plan to address opioid addiction, abuse, and overdose that included increasing the prevalence of abuse-deterrent formulations (ADFs) in opioid tablets. Polyethylene oxide (PEO) has been widely used as an excipient to deter abuse via nasal insufflation. However, changes in abuse patterns have led to unexpected shifts in abuse from the nasal route to intravenous injection. Case reports identify adverse effects similar to thrombotic thrombocytopenic purpura (TTP) syndrome following the intravenous (IV) abuse of opioids containing PEO excipient. Increased risk of IV opioid ADF abuse compared to clinical benefit of the drug led to the removal of one opioid product from the market in 2017. Because many generic drugs containing PEO are still in development, there is interest in assessing safety consistent with generic drug regulation and unintended uses. Currently, there are no guidelines or in vitro assessment tools to characterize the safety of PEO excipients taken via intravenous injection. To create a more robust excipient safety evaluation tool and to study the mechanistic basis of HMW PEO-induced TMA, a dynamic in vitro test system involving blood flow through a needle model has been developed.

1993. Serratia is a rare cause for Infective Endocarditis of the Tricuspid Valve

Abstract Background Serratia marcescens is a Gram-negative motile bacillus that is a facultative anaerobe and non-lactose fermenting. Serratia can be isolated from water, soil, plants, and the intestinal microbiome. Serratia produces a unique Identifying reddish pigment called prodigiosin. Serratia is responsible for only 0.14% of infective endocarditis cases, with a mortality rate of 85%. Methods A 37 YO female with a history of Intravenous heroin abuse was admitted with fevers and dyspnea. Vital signs were BP 76/50, HR 140, RR 26, temp 102 F, and SpO2 98% on room air. She was toxic-appearing. Labs: WBC 26000(4,000 – 11,000 /uL) with 14% bands, Hb 5.6 (12.6 – 17.0 g/dL), PLT 15*10^3(150-372*10^3/uL), creatinine 2.5 (0.50 - 1.60 mg/dL), lactic acid 15.8 (0.5-2.2 mmol/L). We started vancomycin, piperacillin-tazobactam, and norepinephrine for septic shock. A transthoracic echo showed a large mass on the tricuspid valve, and a transesophageal echo depicted it as vegetation. Blood cultures grew Serratia. She underwent excision of anterior and posterior tricuspid valve leaflets with reconstruction and ring annuloplasty. She reported washing her syringes with tab water and reusing them again. Serratia has a predilection for left-side heart valves even in the IVDU population but this patient presented with a tricuspid valve endocarditis. Results Serratia is a rare cause for IE in the ICE study; out of 2.761 definite IE cases identified over five years, only forty-nine instances were due to gram-negative bacilli. Of those, only four cases were due to Serratia. The clinical presentation of Serratia includes constitutional symptoms, new-onset murmur, and cutaneous and neurologic manifestations. Serratia produces multiple pathogenic factors allowing Serratia to result in valvular destruction and perivalvular complications, and distant septic emboli metastasis. Conclusion Serratia is sensitive to third and fourth-generation cephalosporins, monobactams, carbapenems, fluoroquinolones, and aminoglycosides. Treatment is complex due to the production of AmpC B-lactamase, which hydrolyzes third and fourth-generation cephalosporins. The 2005 IDSA suggested a combination of B-lactam and an aminoglycoside for Serratia endocarditis, and these are not guidelines but merely recommendations. Disclosures All Authors: No reported disclosures.

SEROPREVALENCE OF HBsAg, Anti-HBs, Anti-HCV, and Anti-HIV IN PATIENTS WITH ALCOHOL AND SUBSTANCE ABUSE IN AN AMATEM CLINIC IN EASTERN TURKIYE: A SIX-YEAR RETROSPECTIVE EVALUATION

Aim
 Substance abuse and concomitant infections are important causes of morbidity and mortality. Yet, the number of epidemiological studies regarding infectious diseases in people with substance abuse are limited in our country. In this study, the aim was to investigate the frequency of illegal alcohol and substance use in an Alcohol and Drug Research, Treatment and Training Centres (AMATEM) clinic in Turkey as well as the HBsAg, anti-HBs, anti-HCV, and anti-HIV parameters between the years of 2016-2021. 
 Material and Method
 HBsAg, anti-HBs, anti-HCV, and anti-HIV tests were conducted using the ELISA technique in 6881 alcohol and substance use disorder (ASUD). Urine samples from ASUD’s were analyzed for alcohol, cannabis, and cocaine metabolites. The results were evaluated retrospectively. 
 Results
 All of the 6881 ASUD’s were male with a mean age of 32.18±9.66 years. Of the 6881 ASUD’s included in the study, 4107 (59.7%) were opioid addicts; 1479 (21.5%) were mixed drug addicts; 897 (13%) were alcohol addicts; and the rest were addicts with other types of substance use. The mean age of the alcohol users was 45.33±13.03 and the mean age of opioid users was 29.90±7.13. The percentage of opioid addiction in 2016 was 71.2% which dropped to 28.7% in 2021. Meanwhile, the percentage of alcohol addiction was 13.6% in 2016 and increased to 21.4% in 2021; and the percentage of mixed drug use was 8.7% in 2016 and increased to 36.8% in 2021. HBsAg-positivity in opioid users (56.7%) was higher compared to cannabis users (2.6%) and mixed drug users (22.3%). Anti-HCV positivity of opioid users (69.4%) was found to be higher compared to alcohol (9.4%), cannabis (2%), and mixed drug (16.2%) users, and this finding was statistically significant (p=0.0001). Anti-HBs positivity of opioid users (63.1%) was found to be higher compared to alcohol (9.9%), cannabis (3%), and mixed drug (21%) users, and this finding was statistically significant (p=0.0001). Anti-HIV was determined negative in all ASUD’s. The highest rates of HBsAg, anti-HCV and anti-HBs positivity were found in the 26-30 years of age. 
 Conclusion
 These findings indicate a high prevalence of intravenous substance abuse in the 26-30 years age group in our region as well as the high HBV and HCV rates in this patient group.

Oral, intranasal, and intravenous abuse potential of serdexmethylphenidate, a novel prodrug of d-methylphenidate

Objectives Serdexmethylphenidate (SDX) chloride (Cl) is a novel prodrug of d-methylphenidate (d-MPH). These studies evaluated the abuse potential of SDX Cl when administered orally, intranasally (IN), and intravenously (IV). Methods Three randomized, double-blind, placebo- and active-controlled crossover studies were conducted in recreational drug users to evaluate the abuse-related effects of oral SDX (120 and 240 mg) vs. extended-release (ER) d-MPH (80 mg) and phentermine (60 mg); IN SDX (80 mg) vs. d-MPH (40 mg), and IV SDX (30 mg) vs. d-MPH (15 mg). Abuse-related subjective measures, pharmacokinetics, and safety were assessed. Results The primary endpoint of maximum (Emax) Drug Liking (DL) (0–100-point scale) was significantly higher following d-MPH vs. placebo, validating the studies. In the oral study, DL Emax was significantly higher following 80 mg ER d-MPH (Emax = 81.5) than 120 mg SDX (Emax = 62.8, p < .001) and 240 mg SDX (Emax = 63.8, p = .006); and following 60 mg phentermine (Emax = 80.2) than 120 mg SDX (p = .0195), but not 240 mg SDX (p = .0665). DL Emax scores were significantly higher following IN d-MPH vs SDX (Emax = 93.2 vs. 71.0, p < .0001) and following IV d-MPH vs. SDX (Emax = 84.3 vs. 56.6, p = .001). Intravenous SDX was non-inferior to placebo (p = .001) for DL Emax. Secondary endpoints (e.g. Take Drug Again) were generally consistent with the primary endpoint. Maximal and overall d-MPH exposure was lower for SDX than d-MPH for all routes. Adverse events typical of stimulants were more frequent with d-MPH than SDX. Conclusions These findings indicate that the novel d-MPH prodrug, SDX, has lower abuse potential than d-MPH and support its classification as a C-IV controlled substance.

A 54-year-old with dysarthria.

A 54-year-old male with a history of intravenous heroin abuse presented to the emergency department for dysarthria. The patient was initially found down with an unknown last known well time. The patient had a blood pressure of 237/101 mmHg. He was alert with a left-sided gaze preference and right-sided Romberg drift. Labs were remarkable for white blood cell count (WBC) 25.7 103/μl and creatine kinase (CK) 5776. Drug screen was positive for opiates. Computed tomography brain and angiography imaging showed bilateral cerebellar hemispheric ischemia, lateral ventricle dilatation, and a right proximal vertebral artery with non-occlusive diminutive distal flow (Figure 1). Several hours later, the patient subsequently experienced a rapid neurological decline from Glasgow Coma Scale (GCS) 11 (E4V2M5) to GCS7 (E2V1M4), prompting intubation for airway protection. Mannitol and 2% hypertonic saline were administered. External ventricular drain was prepared for potential deterioration. Subsequent magnetic resonance imaging showed stable, bilateral subacute cerebellar infarcts with hydrocephalus (Figure 2) and the patient was ultimately extubated and required prolonged rehabilitation. Bilateral ischemic cerebellar strokes are rare cerebrovascular accidents (CVAs).1 Large volume infarcts have a high risk of developing space-occupying brain edema in the compact posterior fossa—risk of rapid, life-threatening herniation through compression of the brain stem and the fourth ventricle with resultant hydrocephalus.2 Opiate abuse has been described as a rare cause of cerebral ischemia though mechanisms including vasospasm and severe hypoperfusion, rhabdomyolysis via muscle compression, and direct toxicity.3, 4 In our case, stable repeat imaging and an elevated CK suggested a subacute presentation and prompted holding off suboccipital craniectomy given the high likelihood of being outside of the acute edema window for effective surgical intervention.5 A positive drug screen with a known history of intravenous drug abuse point to a rare drug-associated ischemia as a potential etiology. Timing of pathology, repeat imaging and clinical assessment, and maintaining a wide differential, including drug-induced ischemia, in relatively young patients without typical CVA risk factors are essential in management of severe cerebellar strokes with unknown onset.

An Evaluation of the Effect of the OxyContin Reformulation on Unintentional Fatal and Nonfatal Overdose.

Objectives:OxyContin was reformulated with a polyethylene oxide matrix in August 2010 to reduce the potential for intravenous abuse and for abuse by insufflation. The objective of this study was to evaluate the impact of OxyContin’s reformulation on overdose (OD) risk for individuals dispensed OxyContin in comparison to those dispensed other opioids under regular care.Materials and Methods:Three national insurance databases with National Death Index linkage identified OD in individuals with any dispensing of OxyContin or a primary comparator opioid (extended release morphine, transdermal fentanyl, or methadone) between July 2008 through September 2015. A difference-in-differences design was used to compare the pre-post reformulation changes in OD rates for OxyContin versus comparators.Results:A total of 297,836 individuals were dispensed OxyContin and 659,673 individuals were dispensed a primary comparator across the 3 databases. Overall, there was little or no difference in the temporal change in OD incidence in comparators versus OxyContin (Medicaid: adjusted ratio-of-rate-ratios (aRoRs) ranging from 0.90 to 1.05; MarketScan/HIRD: aRoR ranging from 1.10 to 1.22). However, restriction to person-time without concomitant opioid use revealed a modestly greater reduction in OD incidence over time during OxyContin use, as the aRoRs comparing the primary comparators to OxyContin ranged from 1.06 to 1.30 in Medicaid and from 1.64 to 1.85 in MarketScan/HIRD.Discussion:This study did not detect an overall effect of the OxyContin reformulation on OD in insured patients under regular medical care. There is a suggestion of a modestly reduced OxyContin-associated OD risk following the reformulation but only in commercially insured individuals receiving single-opioid regimens.

Paradoxical and Retrograde Air Embolism from Pressurized Peripheral Bolus

Introduction Cerebral air embolism is a rare, yet serious neurological occurrence with unclear incidence and prevalence. Here, we present a case of fatal cerebral arterial and venous cerebral gas embolism in a patient with infective endocarditis and known large right-to-left shunt and severe tricuspid regurgitation following pressurized fluid bolus administration. Case Presentation. A 32-year-old female was admitted to the medical intensive care unit from a long-term acute care facility with acute on chronic respiratory failure. Her medical history was significant for intravenous heroin and cocaine abuse, methicillin-sensitive Staphylococcus aureus tricuspid valve infective endocarditis on vancomycin, patent foramen ovale, septic pulmonary embolism with cavitation, tracheostomy with chronic ventilator dependence, multifocal cerebral infarction, hepatitis C, nephrolithiasis, anxiety, and depression. After intravenous fluid administration, she became unresponsive with roving gaze, sluggish pupils, and hypotensive requiring vasopressors. CT of the brain showed diffuse arterial and venous cerebral air embolism secondary to accidental air administration from fluid bolus. Magnetic resonance imaging of the brain showed diffuse global anoxic injury and flattening of the globe at the optic nerve insertion. Given poor prognosis, her family chose comfort measures and she died. Conclusions Fatal cerebral air embolism can occur through peripheral intravenous routes when the lines are inadequately primed and fluids administered with pressure. Caution must be exercised in patients with right-to-left shunting as air may gain access to systemic circulation.

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.

OSTEOMYELITIS OF FEMUR IN A DRUG ADDICTED CHILD

One of the serious complications related to intravenous drug use is osteomyelitis. We report a 13-year-old male child with a history of intravenous heroin abuse, who was admitted to the hospital complaining of abdominal pain and pain in the left leg. Anteroposterior roentgenogram and CT scan of the left thigh and femur, confirmed the diagnosis of osteomyelitis. Pus culture was positive for Staphylococcus aureus. Despite extensive antibiotic and anticoagulant therapy, the patient’s clinical status improved very slowly. Surgical procedure was not undertaken. Femoral osteomyelitis due to injection drug use in childhood is an extremely rare and uncommon condition. Intravenous drug abuse, late-onset treatment, and secondary bacterial infection can lead to complications which occurred in the case presented. It is an extremely difficult condition to treat and is a real challenge for physicians. The rapid response and participation of a multidisciplinary team of physicians is of particular importance. Key words: antibiotics, children, femur, osteomyelitis, staphylococcus aureus.

Aspiration in lethal drug abuse\u2014a consequence of opioid intoxication

AimsThe primary objective of this study was to investigate whether the fatalities of opioid abuse are not only related to respiratory depression but also as a result of other side effects such as emesis, delayed gastric emptying, a reduction of the cough reflex, and impaired consciousness leading to the aspiration of gastric contents, a finding regularly observed in drug-related deaths.DesignA retrospective exploratory study analyzing heroin/morphine/methadone-related deaths submitted to court-ordered autopsy.SettingCenter for Forensic Medicine, Medical University of Vienna, Austria (2010–2015).ParticipantsTwo hundred thirty-four autopsy cases were included in the study: morphine (n = 200), heroin (n = 11), and methadone (n = 23) intoxication.FindingsAnalyses revealed that 41.88% of all deceased showed aspiration of gastric contents with equal gender distribution (p = 0.59). Aspiration was more frequent in younger deceased (χ2 = 8.7936; p = 0.012) and in deceased with higher body mass index (BMI) (χ2 = 6.2441; p = 0.044). Blood opioid concentration was lower in deceased with signs of aspiration than in non-aspirators (p = 0.013). Toxicological evaluation revealed a high degree of concomitant substance abuse (91%)—benzodiazepines (61.6%) and/or alcohol (21.8%).ConclusionsThere are lower opioid concentrations in deceased with signs of aspiration, a fact which strongly points to aspiration as alternative cause of death in opioid-related fatalities. Furthermore, this study highlights the common abuse of slow-release oral morphine in Vienna and discusses alternative medications in substitution programs (buprenorphine/naloxone or tamper-resistant slow-release oral morphine preparations), as they might reduce intravenous abuse and opioid-related deaths.

Tobacco smoke and morphine alter peripheral and CNS inflammation following HIV infection in a humanized mouse model

Tobacco smoking is common in HIV-infected patients, and is prevalent among intravenous opiate abusers. Conversely, intravenous opiate abusers are more likely HIV-infected, and opiate abuse is associated with more severe neuroinflammation. Given the coincident use of tobacco smoking among HIV-infected intravenous drug users (IVDUs), we set out to study the effects of smoke exposure, chronic morphine administration, and HIV infection using the NSG humanized mouse model. Our results show that smoke, morphine, and the combination promotes the decline in CD4+ T cells in HIV-infected mice. Further, chronic morphine administration increases the numbers of circulating CD8+ T cells which express the inhibitory receptor PD-1, as well as the cytolytic proteins perforin and granzyme B in the infected mice. We also found that the combination of smoke and morphine inhibited the expression of IL-1α, IL-4 and IL-17A. Finally, the combination of smoke and morphine exposure induces microglial activation following infection, as well as in the absence of HIV infection. To our knowledge, this is the first report to assess the combined effects of smoke and chronic morphine exposure on the inflammation associated with HIV infection, and demonstrate that these two insults exert significant neuroinflammatory activity.

Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation.

The objective of the present study was to develop extended-release (ER) hot-melt extruded (HME) abuse-deterrent pellets of acetaminophen, a model drug, by utilizing high molecular weight polyethylene oxide (PEO) and gelling agents (xanthan gum, guar gum, and gellan gum). The HME pellets were evaluated for their abuse-deterrence (AD) potential by Category-1 laboratory in-vitro evaluation parameters, including particle size reduction (PSR), small volume extraction, dissolution, viscosity, syringeability, and injectability. Further, the pellets were investigated for resistance to physical (crushing) and thermal (oven and microwave) manipulation to evaluate the strength of the AD properties. Physical manipulation studies demonstrated that the pellets were intact, extremely hard, and resistant to PSR and manipulation to bypass ER properties. Dissolution of all intact and physically manipulated pellets led to complete drug release within 8h, and resistance to dose-dumping in 40% ethanol was observed. The drug extraction was <50% in 10mL of ingestible and non-ingestible solvents under static, agitation, and thermal manipulation conditions with an incubation time of 30min. The PEO/xanthan gum-based formulation showed higher viscosity, syringe and injection forces, and lower syringeable volume in all manipulation conditions compared with plain PEO pellets. These findings supported the AD potential of PEO and xanthan gum pellets against intravenous abuse.

Polyethylene Oxide Molecular Size Determines the Severity of Atypical Thrombotic Microangiopathy in a Guinea Pig Model of Acute Intravenous Exposure.

In 2017, Opana ER was voluntarily removed from the U.S. market based on concerns that its risks outweighed its therapeutic benefits. The data that supported this conclusion were based on postmarketing evaluation that demonstrated increased intravenous abuse associated outbreaks of HIV, hepatitis C, and uniquely, a thrombotic thrombocytopenic purpura (TTP)-like syndrome. In 2017, the cause was mechanistically linked to intravenous exposure of the high-molecular weight polyethylene oxide (PEO), an excipient component of the drug product. However, it was unknown how differing PEO preparations might alter this response in vivo. Knowing the likelihood of a PEO driven atypical thrombotic microangiopathy with hemolytic uremic syndrome (TMA-HUS), this study was specifically designed with the primary objective focused on understanding the impact of PEO molecular weight on TMA-HUS in a guinea pig model of acute repeat PEO (1, 4, and 7 MDa) dosing. Results from this analysis suggest that repeated dosing with PEO 4 and 7 MDa, but not 1 MDa induced a marked intravascular hemolysis with schistocytes, mild anemia, thrombocytopenia, hemoglobinuria, and kidney injury, consistent with observations of a TMA-HUS-like syndrome. Nonetheless, observations of tissue microthrombi, complement or altered von Willebrand factor involvement were not observed, which would be consistent with a definitive TMA. Further, only 7 MDa PEO dosing was associated with marked renal hypoxia. Taken together, this study defines renal injury risk with PEO formulations >1 MDa that is driven by a robust intravascular hemolysis and potentially, tissue hypoxia.

Tapentadol abuse and dependence in India.

Tapentadol is a synthetic opioid analgesic available in India since 2011. International evidence suggests a low risk of abuse and diversion. Our study aims to question this perception in Indian context. We report the trend and profile of Tapentadol abuse cases that were treated at a tertiary level addiction treatment centre in southern India. We also describe the ease of repurposing oral tablets of Tapentadol into an injection. At the national level, we have examined the temporal and spatial trends of online interest in Tapentadol and compared it with a non-opioid drug Ilaprazole and an opioid drug Tramadol using Google Trends. We have used the National Drug Use Survey 2019 to illustrate the regional data. 23 cases of Tapentadol abuse sought treatment between 01/01/2011 and 30/08/2019. In last one year, the number of cases has more than doubled. A majority (N = 19, 83 %) of cases had intravenous Tapentadol abuse, needle sharing and 60 % were diagnosed with Hepatitis C. Tapentadol is attracting new users (N = 13, 56.5 %) as well as replacing other opioids (N = 10, 43.5 %) amongst drug users. Tapentadol has received more online interest than Ilaprazole. Temporal and spatial trends of online interest in Tapentadol parallel Tramadol. States with high prevalence of opioid users have shown high online interest in both opioid drugs. Tapentadol is being widely abused, and urgent regulatory measures are required.

Development of an in vitro system and model-based translational framework to assess haemolysis risk following intravenous abuse of medications containing polyethylene oxide

Multiple cases of potentially life-threatening thrombotic microangiopathy (TMA) have resulted from intravenous abuse of medications containing polyethylene oxide (PEO), most often Opana ER (oxymorphone hydrochloride extended release). No validated models are available to assess the risk of TMA with different formulations and extraction methods following intravenous abuse. We have developed an in vitro system that involves passing pooled blood containing the excipient of interest through a syringe needle and assessing haemolysis via haemoglobin release. Haemolysis is induced by high shear stress caused by the flow of blood containing PEO through a narrow-bore syringe needle, recapitulating the mechanism in small blood vessels. Using the in vitro system, we demonstrate that high-molecular-weight PEO (>1 MDa) induces haemolysis in a concentration-dependent manner under flowing but not static conditions. We use data from the in vitro system and published in vivo data to predict the time course of the haemolytic response in vivo via a pharmacometric model. The in vitro system is a novel method for investigating factors influencing PEO-induced haemolysis. In combination with our model-based translational framework, the in vitro system allows straightforward assessment of the haemolytic potential of PEO-containing medications, and may find application in gauging TMA risk following intravenous abuse.

Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers

An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of “homemade” methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the ‘homemade’ drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the ‘homemade’ mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced 123I-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the ‘homemade’ mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man.

Caractéristiques des plaies chroniques chez les toxicomanes : étude rétrospective de 58 patients

Drug addiction causes chronic wounds (CW) responsible for severe complications. Very few studies are available on this topic. The aim of our study was to describe the demographic, clinical and etiological characteristics as well as the course of CW in drug addicts. This was a retrospective and prospective multicenter study including all drug addicts with CW. We included 58 patients (17 prospectively), 84.5% of whom were male, of median age 43 years, presenting multiple CW as a result of intravenous (78.2%), inhaled (41.1%) and/or snorted (20%) drug abuse. Addiction to opioids (68.4%), cocaine (47.4%) and/or cannabis (40.4%) was ended and/or treated through substitution in 79.3% of patients. CW were fibrinous and necrotic (42.9 to 53.6%), recurrent (54.2%), and in some cases had been present for more than 1 year (61.5%). Intravenous drug addiction was associated with large, fibrinous, ulcers in a setting of venous and lymphatic insufficiency (74%). Only 23% of these wounds involved the upper limbs. Necrotic ulcers associated with clinical arteriopathy were described mainly with inhaled addiction. Abscesses (50%) and erysipelas (29.3%) were the most common cutaneous complications. After 3 months, 50% of CW were improved and 29.2% of patients were lost to follow-up. Drug abuse-related CW occurred preferentially in young men with history of intravenous abuse. For the most part, CW were seen on the legs and were associated with venous and lymphatic insufficiency, and the resulting major risk for cutaneous infection increased morbidity and mortality in this population in whom medical follow-up is inherently complicated.

PULMONARY CAVITARY LESION WITH RARE PSEUDOMONAS STUTZERI

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pseudomonas stutzeri is a gram-negative rod bacterium infrequently associated with clinical infection. We present a case of pulmonary cavitary lesions caused by P.stutzeri. CASE PRESENTATION: A 59-year-old male with history significant for intravenous (IV) heroin abuse (last use 1 week prior), splenectomy and culture negative endocarditis (10 months prior) presented to the hospital with 1 week of chest pain, dyspnea and subjective fevers. Within a few hours of admission, a rapid response was called for altered mental status, chest pain and tachypnea. Computed tomography of the chest revealed a 12cm cavitary left lower lung lesion. He was placed on tuberculosis precautions and subsequently transferred to the Intensive Care Unit (ICU) for further management. Blood cultures were obtained prior to empiric vancomycin plus piperacillin/tazobactam. He required intubation for impending respiratory failure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed demonstrating copious mucus and purulent secretions bilaterally. Approximately 36 hours into his admission, he suffered a PEA (pulseless electrical activity) arrest. Return of spontaneous circulation (ROSC) was achieved after 15 minutes of cardiopulmonary resuscitation (CPR). Physical exam revealed diffuse crepitus, subcutaneous emphysema tracking along posterior thorax extending into left lateral thigh and profound scrotal swelling. Arterial blood gas demonstrated acidemia with hypercarbia. Within less than an hour, he suffered a second PEA arrest. There was concern for ruptured pleural cavitary lesion leading to a tension pneumothorax. Needle decompression performed bilaterally was unsuccessful; surgery at bedside placed left hemithorax chest tube. Again, achieved ROSC after 18 minutes of CPR. Unfortunately, within a few minutes he decompensated into ventricular fibrillation. Further resuscitation efforts a third time were unsuccessful. Post-mortem blood cultures were negative but his BAL cultures were positive for pan-sensitive Pseudomonas stutzeri. All acid-fast bacilli smears and cultures were negative. DISCUSSION: Pseudomonas stutzeri has rarely been reported as a cause of necrotizing pneumonia (1) and may represent only 1% of all clinical Pseudomonas isolates (2). In our patient, the timeline of events, whether the cavitary lesion ruptured from the positive pressure of mechanical ventilation or as a consequence of CPR remains a mystery. CONCLUSIONS: There is debate in the literature regarding the pathogenicity of this organism which is frequently deemed to be colonization rather than pathogenic. However, in the case of this patient, all other infectious work up was negative and no alternative pathogen could be linked to the development of the cavitary lesions. This case emphasizes the necessity of diagnostic testing to identify uncommon pathogens. Reference #1: Lin KH et al, Pseudomonas stutzeri necrotizing pneumonia in pre-existing pulmonary tuberculosis. Intern Med. 2014;53(21):2543-6. 2014 Nov 1. Reference #2: Bisharat, N et al, 10-Years Hospital Experience in Pseudomonas stutzeri and Literature Review. The Open Infectious Diseases Journal, 2012, 6, 21-24. DOI: 10.2174/1874279301206010021 DISCLOSURES: No relevant relationships by Zachary Bugos, source=Web Response No relevant relationships by Brandon Smith, source=Web Response