Heroin Research Articles

Safety and feasibility of intranasal heroin-assisted treatment: 4-week preliminary findings from a Swiss multicentre observational study

BackgroundHeroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM.MethodsThis is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated.ResultsParticipants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported.ConclusionsAfter four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.

Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses.

Neutrophils display an array of biological functions including the formation of neutrophil extracellular traps (NETs), web-like structures specialized in trapping, neutralizing, killing and preventing microbial dissemination within the host. However, NETs contribute to a number of inflammatory pathologies, including severe equine asthma. Tamoxifen (TX) is a selective estrogen receptor modulator which belongs to the triphenylethyllenes group of molecules, and which is used as a treatment in all stages of estrogen-positive human breast cancer. Our previous results suggest that tamoxifen can modulate neutrophil functionality and promote resolution of inflammation; this would partly explain the clinical beneficial effect of this drug in horses with airway inflammation. Enhanced NETs production has been reported with tamoxifen use in humans, but minimal data exists regarding the drug's effect on NETs in horses. The aim of this study is to assess the in vitro effect of TX on NETs formation from peripheral blood of healthy horses. Five clinically healthy mixed-breed adult horses were enrolled in the study. For this, cellular free DNA quantification, immunofluorescence for the visualization of NETs, assessment of different types of NETs, and detection of mitochondrial superoxide. TX induced NETs formation at a concentration of 10 uM. Our results show that only two types of NETs were induced by TX: 95% spread NETs (sprNETs) and 5% aggregated NETs (aggNETs). Furthermore, induction of these NETs could be influenced by mitochondrial ROS. Future research should involve an In vivo study of horses with severe asthma and TX treatment, to evaluate BALF neutrophil NET formation. In conclusion, this in vitro study suggests that the resolution of inflammation by TX in horses with airway inflammation is due to inhibition of other neutrophilic functions but not to NET formation.

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.

Comparative Study of the effect of time duration of marijuana and heroin abuse on concept formation

The present study was conducted to assess the effect of time duration of heroin and marijuana abuse on concept formation in a comparative manner which based on a sample of 90 people from three different groups. This group represents the involvement of heroin and marijuana abuse in a different time periods that was 2 years, 4 years and 6 years. Purposive selection method was taken for allotment the subjects. . The responses of the subjects are measured and tabulated by standardized tests. The analysis of variance was used in the present study. The purpose of the study was to find out the causal relationship along with the difference between the time duration of heroin and marijuana abuse on concept formation and the results indicates that there was significant difference at 0.01level.

Transcriptomics and metabolomics together reveal the underlying mechanism of heroin hepatotoxicity

Researches on heroin are more about addiction and some infectious diseases it causes, but liver fibrosis caused by heroin abuse and the mechanism of heroin hepatotoxicity in addicts are ignored. To explore the mechanism of heroin hepatotoxicity, mice in heroin group were intraperitoneally injected by heroin (10 mg/kg) once a day for 14 consecutive days, while mice in heroin withdraw group underwent another 7 days without heroin administration after the same treatment as heroin group. The levels of alanine aminotransferase （ALT）and aspartate aminotransferase （AST） in serum, as biochemical indexes, were applied to evaluate liver damage. H & E staining and oil red O staining were used to observe the pathological changes of liver. Transcriptomics and metabolomics were applied to detect genes and metabolites in livers. The results of biochemical analysis and pathological examination showed that heroin induced liver damage and lipid loss in mice, and these mice did not return to normal completely after a short-term withdrawal. A total of 511 differential genes and 78 differential metabolites were identified by transcriptomics and metabolomics. These differential genes and metabolites were significantly enriched in pathways like lipid metabolism, arachidonic acid metabolism, glutathione metabolism, TCA cycle. And after undergoing 7-day withdrawal of heroin, most of the above differential genes and metabolites did not return to normal. Our study revealed the hepatotoxicity of heroin and that short-term withdrawal of heroin did not fully restore liver function. In addition, transcriptomics and metabolomics revealed that lipid metabolism and arachidonic acid metabolism may be potential therapeutic targets of heroin hepatotoxicity, providing a basis for the treatment of heroin addiction patients in the future.

Gaps and barriers in drug and alcohol treatment following implementation of the affordable care act

BackgroundThis study examines changes in the substance use disorder (SUD) treatment gap and barriers to treatment for low-income adults following Affordable Care Act (ACA) implementation. MethodsNational Survey on Drug Use and Health (NSDUH) data were pooled to assess pre-ACA (2009–2013) and post-ACA (2015–2019) implementation. The sample (n = 44,622) included respondents 18–64 years old, income <200% federal poverty level, and meeting SUD criteria for abuse or dependence of heroin, powdered cocaine, crack cocaine, marijuana, or alcohol. The primary outcome was NSDUH-defined past-year illicit drug or alcohol treatment gap (needing but not receiving SUD specialty treatment). A secondary analysis assessed barriers to SUD treatment including insurance-related barriers, stigma, barriers to access, priority of treatment, and no interest in stopping substance use. ResultsNinety-three percent of respondents reported a drug or alcohol treatment gap before and after ACA implementation. No interest in stopping use was the greatest barrier (40%), followed by insurance-related barriers (39%) and stigma (20%). After adjusting for covariates, results did not show a significant change in SUD treatment gap post-ACA compared to pre-ACA (adjusted odds ratio [aOR]=1.11, 95% confidence interval [CI]=0.97, 1.28, p = 0.13). Compared to pre-ACA, odds of reporting stigma-related barriers (aOR=1.66, 95% CI=1.17, 2.37, p = 0.01) and access-related barriers (aOR=1.79, 95% CI=1.34, 2.38, p < 0.001) increased post-ACA. ConclusionsThere was no significant change in the prevalence of SUD treatment gap after ACA implementation. Increasing access to SUD treatment for low-income individuals will require intervening at multiple socioecological levels beyond reforming treatment financing.

An Unusual Case of High 6-Monoacetylmorphine and Low Morphine in Urine: Heroin Abuse or Analytical Error?

A 59-year-old male with a past medical history of chronic low back pain, opioid use disorder, and type 2 diabetes mellitus presented to an outpatient clinic for pain contract–related urine drug screen testing. Current medications included metformin, oxycodone, and Suboxone® (buprenorphine and naloxone combination). The patient stated that 5 days prior to the visit, he stopped taking Suboxone due to complaints of nausea and vomiting. Urine toxicology test results are summarized in Table 1. ... ... Suboxone is an opioid abuse management medication that is formulated with buprenorphine and naloxone. Naloxone has limited bioavailability when administered sublingually and should be barely detectable in urine. However, when Suboxone is taken parenterally, naloxone enters the blood stream and is largely excreted in urine. In this case, the presence of a high concentration of naloxone in urine with a high ratio to buprenorphine suggested parenteral administration (1). Heroin is readily metabolized into 6-MAM and then to morphine. Typically, the 6-MAM-to-morphine ratio is <0.26, so it is uncommon to see a high positive 6-MAM with very low morphine concentrations (2). The calculated 6-MAM-to-morphine ratio in this sample was 7.27. Conversion from morphine to 6-MAM due to contaminants in enzyme hydrolysis or acid hydrolysis used during sample preparation in urine samples with extremely high morphine (>100 000 μg/L) has been reported (3). In our case, morphine was very low, so this was unlikely, but to rule out any analytical cause, the positive urine sample was sent to a reference laboratory, which confirmed our findings. The fact that 2 laboratories using different mass spectrometry–based methods showed detectable 6-MAM supported heroin use, instead of a false positive due to an interference. The unusually low morphine result in some heroin users has been reported elsewhere and may be mostly attributed to inhibitors of carboxylesterases from the heroin synthesis process (2) or explained by polymorphism in the esterase enzymes metabolizing 6-MAM to morphine (4). The physician also requested serum fentanyl testing by mass spectrometry 5 days after the original urine sample collection (fentanyl was not part of our general urine drug screen), which came back positive for fentanyl and norfentanyl. In addition to the unexpected positive amphetamine result, all of this confirmed that this patient suffered from polysubstance abuse.

Development of an Effective Monoclonal Antibody against Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine and Morphine over Heroin.

The opioid epidemic is a global public health crisis that has failed to abate with current pharmaceutical treatments. Moreover, these FDA-approved drugs possess numerous problems such as adverse side effects, short half-lives, abuse potential, and recidivism after discontinued use. An alternative treatment model for opioid use disorders is immunopharmacotherapy, where antibodies are produced to inhibit illicit substances by sequestering the drug in the periphery. Immunopharmacotherapeutics against heroin have engaged both active and passive vaccines targeting heroin’s metabolites, 6-monoacetylmorphine (6-AM) and morphine, since decades of research have stated that heroin’s psychoactive and lethal effects are mainly attributed to these compounds. However, concerted efforts to develop effective immunopharmacotherapies against heroin abuse have faced little clinical advancement, suggesting a need for reassessing drug target selection. To address this issue, four unique monoclonal antibodies were procured with distinct affinity to either heroin, 6-AM, or morphine. Examination of these antibodies through in vitro and in vivo tests revealed monoclonal antibody 11D12 as the optimal therapeutic and provided crucial insights into the key chemical species to target for blunting heroin’s psychoactive and lethal effects. These findings offer clarification into the problematic attempts of therapeutics targeting heroin’s metabolites and provide a path forward for future heroin immunopharmacotherapy development.

Can Heroin Poisoning Lead to Stomach Necrosis? A Case Report

Background: According to the last report of the United Nations Office on Drugs and Crime (UNOCD), opiate use (including heroin) is 1.2% of the world population. In Iran, about 2 million people are drug addicts. Heroin reduces gastric motility and prolongs gastric emptying time and causes gastric dilation which can be a reason for gastric ischemia. Gastric ischemia is an uncommon condition due to the rich gastric blood perfusion and collateral arteries. As some studies show, gastric dilation can be the cause of gastric necrosis. Methods: A 22-year-old woman presented to our hospital with severe abdominal pain and several episodes of vomiting. The patient declared that she had a history of addiction to methamphetamine and heroin. Abdominal examination revealed a soft and non-distended abdomen with generalized tenderness, mostly in the hypogastric region without rebound tenderness. Abdominal radiograph revealed that the stomach was highly distended. Abdominal CT without contrast confirmed severe gastric dilatation. In endoscopy, multiple necrotic lesions were seen throughout the stomach and mostly in the proximal part. Our finding in the laparotomy was gastric necrosis in the proximal part, which resulted in a total gastrectomy. Esophagojejunostomy was performed with roux en y reconstruction after total gastrectomy. Conclusion: Opioids can increase the risk of gastrointestinal (GI) dysfunction and can increase the risk of infection in the GI tract. In our case, heroin abuse caused gastric dilation and massive gastric necrosis.

Septic Tenosynovitis of the Lower Extremity: A Case Report

Category: Other Introduction/Purpose: Tibialis anterior rupture is an exceptionally rare complication of septic tenosynovitis. One case of septic tenosynovitis of TA has been previously documented by Lowell et al. 2020 It is worth noting in this case, that TA was unruptured. In this abstract, we present a case of TA rupture secondary to septic tenosynovitis. Methods: A 46-year-old female with a past medical history of depression, HIV, HCV, Diabetes Mellitus, medication noncompliance and current heroin abuse presented with 2 days of right ankle pain. She also reported fever, chills, diaphoresis, nausea and vomiting. She was diagnosed with right foot cellulitis based on clinical findings of erythema, induration and tenderness. She underwent computed tomography (CT) with contrast of her right lower extremity which showed a peripherally enhancing fluid collection surrounding the tibialis anterior tendon consistent with tenosynovitis. There appeared to be medial extension beyond the tendon sheath (Figure 1). A sagittal view is provided in Figure 2, which further demonstrates the fluid collection. Results: She had an I&amp;D of the fluid collection and started on IV vancomycin. After admission to the medical floor, blood cultures were drawn. The patient failed to improve after 2 days of vancomycin therapy. The blood cultures were negative. She subsequently had MRI of her right lower extremity that showed a persistent peripherally enhancing fluid collection anterior to the tibialis anterior tendon and high-grade partial tear of the tibialis anterior tendon (Figure 3). She was then taken to the operating room for a repeat incision and drainage where the tendon sheath of the tibialis anterior was incised and the tendon was exposed with washout. Wound cultures were drawn, and afterward, her antibiotic regimen was broadened with Piperacillin-Tazobactam. She was taken back to the operating room a third time for primary closure of the wound. Wound cultures grew methicillin- sensitive Staphylococcus Aureus resistant to clindamycin and she was discharged on Bactrim. Conclusion: Septic or suppurative tenosynovitis is the infection and inflammation of the closed synovial sheath of a tendon. These infections typically involve the tendons and tendon sheaths of the flexor muscles in the hand. The potential spaces of tendon sheaths create a walled-off environment ideal for pathogens to grow in isolation from host defenses. he pathogenesis of septic tenosynovitis typically involves trauma from a laceration, puncture or bite but other cases of disseminated hematogenous spread have been reported (Newman et al., 1989). Both medical and surgical management is recommended for the best possible outcome.

Case report of toxic leukoencephalopathy induced by heroin abuse

Toxic leukoencephalopathy is a rare disease that may present with different signs and symptoms, it requires a combination of clinical signs and symptoms along with radiographic evidence to reach a diagnosis. We report the case of a young man who presented with a decreased level of consciousness and found that he took an overdose of heroin prior to admission, after investigations the patient was found to have toxic leukoencephalopathy. Its an uncommon disease, however, it should be in the differential diagnosis of any patient coming with some neurological and behavioral changes along with substance abuse, mainstay treatment is supportive.

Estudio transversal retrospectivo de la evolución del consumo de opioides farmacológicos y de heroína en un grupo poblacional del área de Barcelona

BackgroundOpioid dependence is causing an epidemic in the US, but unlike the 1970s it seems more related to prescription opioids than heroin. ObjectivesThe objective of this study is to assess whether this new epidemic has already reached our environment and to see if there are changes in consumption and in the characteristics of consumers. Patients and methodsRetrospective cross-sectional study. 1,140 patients were included between 2012 and 2019, 633 of whom were first visits to Drug Addiction Care and (CAS) Monitoring Centers, 502 corresponding to emergency room visits for problems related to overdose or withdrawal of heroin or opioids with prescription, and the remaining 5 are newborns of mothers addicted to heroin. Demographic data and characteristics of the substances of abuse were analyzed, comparing between partial periods. ResultsThere was a global decrease in the first visits of patients to the CAS who reported heroin addiction (P=.001), while those addicted to pharmacy opioids have remained stable. There has been an irregular increase in total emergency visits, overdose consultations, and withdrawal consultations, both for heroin and prescription opioids (P=.062, P=.166 and P=.005, respectively). Opioid-related emergencies have been less frequent than for heroin. Non-Spanish European patients have increased compared to Spanish patients. ConclusionThere has been no worrying increase in heroin or prescription opioid abuse in our setting.

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6‐diacetyl ester of morphine (diacetylmorphine). The post‐mortem diagnosis of heroin‐related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post‐mortem anti‐6‐MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin‐related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post‐mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Occurrence, distribution, and ecological risk of psychoactive substances in typical lakes and rivers in Qinghai-Tibet Plateau

The occurrence, distribution, and ecological risks of psychoactive substances (PSs) in Qinghai-Tibet Plateau (QTP) was investigated in this study. The surface water samples were collected in July in 2020 from five major water bodies, and 9 PSs were determined by liquid chromatography-mass spectrometry. The mean concentrations of the total PSs were 2.19–96.86 ng/L in lakes and 4.56–34.47 ng/L in rivers. Amphetamine (AMP) was the predominant contaminant both in lakes and rivers with a mean concentration of 12.21 ± 22.76 ng/L and 9.83 ± 6.14 ng/L, respectively. The compositions of PSs in lakes and rivers were significantly different. AMP, methadone (MTD), 3,4-methylenedioxyamphetamine (MDA), and ketamine (KET) were the most detected contaminants in lakes, while in rivers AMP, MDA, heroin (HER), and methamphetamine (METH) were the most detected ones. Concentrations of AMP and MTD, the two predominant drugs, varied spatially, with the decreasing concentration of AMP in the order of Huangshui River > Yamzhog Yumco Lake > Qinghai Lake > Lhasa River > Namco Lake, and of MTD in the order of Qinghai Lake > Namco Lake > Huangshui River > Yamzhog Yumco Lake. The risk quotients (RQs) of PSs ranged from 4.44 × 10−6 to 4.32 × 10−2, indicating a low risk of PSs in the aquatic ecosystem in QTP. Compared with other research in the world, the contamination of psychoactive substances in the Qinghai-Tibet Plateau was at relatively low levels with low ecological risks.

SOCIO DEMOGRAPHIC AND CLINICAL PROFILE OF INJECTABLE OPIOID ABUSERS IN A HOSPITAL BASED POPULATION

Background: Substance use disorder is a highly prevalent disorder causing both social and personal burden on the individual. Opioid use disorder affects the huge population around the world. To study the socio demographic andAim: clinical prole of injectable opioid users in a hospital based population. It was a cross sectional study. The duration of the study was forMethods: 1 year from1st June 2019 to 31st May 2020.100 patients of injectable opioid users with opioid dependence from Out Patient Department and Indoor Patient Department of Psychiatry,Gauhati Medical College and Hospital who fullled the selection criteria and gave written informed consent were recruited for the study. Data were analysed using descriptive statistical method. The Mean age of theStatistical analysis: Results: study sample is 24.72 years. All the study sample were male. Majority of patients (79%) were from Hindu religion.44% of patients were self- employed.76% of study subjects were unmarried.55% of patients were from lower middle socio economic status.77% of patients were from nuclear family. Majority of patients (66%) have tattoo over their body. 59% of patients share needle with partner while taking injectable opioids. 38 % patients started injecting opioids before 18 years of age. Majority of patients (56%) had Hepatitis C Virus reactive status. Conclusion: From our study we could able to nd out different socio demographic and clinical prole of injectable opioid users. From this study it is also reected that 38% of study population started heroin injection during their adolescent period. Hence the early detection and treatment of these adolescent heroin abusers need urgent intervention.

Platelet-To-Lymphocyte and Neutrophil-To-Lymphocyte Ratios Predict Intestinal Injury in Male Heroin Addicts.

Objective To explore the potential link between gut damage and proinflammatory cytokines in heroin-dependent patients. Methods We retrospectively analyzed and compared partial blood counts and biomarkers of intestinal injury and their potential correlations in 38 male heroin abuse patients and 29 healthy male participants. In addition, we compared and assessed proinflammatory cytokines and immune cells in 10 heroin abuse patients and 10 healthy participants. Results Neutrophil counts, platelets/lymphocytes (PLR), neutrophils/lymphocytes (NLR), gut injury biomarkers, and proinflammatory cytokines, CD19+B in patients compared with healthy subjects' cells increased significantly. The number of lymphocytes, CD3 CD4 T cells, and CD3 CD8 T cells decreased in patients compared to healthy individuals. When distinguishing between heroin addicts and healthy people, ROC/AUC analysis showed that a cutoff of 142.42 for PLR and 2.18 for NLR yielded a sensitivity of 65% and 85% and a specificity of 96.5% and 89.7%, respectively (p = 0.001, p < 0.001). For predicting intestinal injury, ROC/AUC analysis showed that a cutoff of 135.7 for PLR and 0.15 for NLR yielded a sensitivity of 52% and 60% and a specificity of 82% and 86.4%, respectively (p = 0.003, p = 0.009). Male heroin addicts are subject to intestinal injury and present with increased proinflammatory cytokine levels. Conclusion NLR and PLR are possible indirect biomarkers for heroin dependence based on intestinal injury.

Pharmacokinetics of grapiprant and effects on TNF-alpha concentrations following oral administration to horses.

Grapiprant is a prostaglandin E2 receptor antagonist that has been found to be an effective anti-inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses received a single oral administration of 15 mg/kg. Plasma concentrations were determined for 96 h using liquid chromatography-tandem mass spectrometry. Non-compartmental analysis was used to determine pharmacokinetic parameters. Pharmacodynamic effects were assessed ex vivo by stimulating blood samples with PGE2 and determining TNF-ɑ concentrations. Maximum concentration, time to maximum concentration and area under the curve were 327.5 (188.4-663.0) ng/ml, 1 (0.75-2.0) hour and 831.8 (512.6-1421.6) h*ng/ml, respectively. The terminal half-life was 11.1 (8.27-21.2) hr. Significant stimulation of TNF alpha was noted for 2-4h post-drug administration. Results of this study suggest a short duration of EP4 receptor engagement when administered at a dose of 15 mg/kg.

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.

Substance Abuse Associated with Aggressive/Violent Behaviors in Psychiatric Outpatients and Related Psychotropic Prescription

Psychiatricdisorders with substance abuse are considered the leading causes of most violent and aggressive behaviors in the general population. This study was aimed to assess the impact of substance abuse and the therapeutic approaches adopted by psychiatrists in aggressive vs non-aggressive outpatients (n = 400) attending community-based psychiatric services and recruited over a 3-year period. Clinical and therapeutic variables were collected from medical records and the Modified Overt Aggression Scale (MOAS) was used to assess any aggressive/violent behavior. Violent behaviors were significantly higher in alcohol and substance abusers compared to non-abusers (p < 0.01), except for heroin abusers. Mean weighted MOAS score was significantly higher in patients taking antipsychotics (p < 0.005). The administration of Haloperidol, Zuclopenthixol, and Clozapine was more frequent in aggressive than in non-aggressive patients. The most frequently administered drug in these patients was Haloperidol (23.91%), with a higher mean daily dosage in violent vs non-violent patients. Our results confirm the well-established relationship between substance abuse and violent behaviors in psychiatric inpatients also within outpatient community services. Observed rates of most frequently prescribed antipsychotics to aggressive patients did not show any preference for newer generation compounds, with clinicians operating in the community setting likely being in need for further evidence and specific training to support their treatment choice.

MO202: Pulmonary-Renal Syndrome in Patient with Chronic Hepatitis C And HIV Disease

Abstract BACKGROUND AND AIMS Pulmonary-renal syndrome (PRS) is characterized by rapidly progressive glomerulonephritis and lung vasculitis. Most common causes of PRS are Goodpasture's disease, antineutrophil cytoplasm antibody (ANCA) associated vasculitis and systemic lupus erythematosus; rarely it could be caused by cryoglobulinemic vasculitis. ANCA and cryoglobulins are present in a wide range of infectious, inflammatory and malignant conditions with or without evidence of clinical vasculitis. ANCA positivity has been described in patients with human immunodeficiency virus (HIV) or chronic hepatitis C (HCV), but only a negligible proportion of these patients developed true ANCA vasculitis. Cryoglobulinemia is seen in ∼50% of patients with HCV and ∼5% of these patients have symptomatic disease. According to previous studies, rapidly progressive glomerulonephritis and pulmonary involvement are rare manifestations of cryoglobulinemia. We describe a patient with HIV and HCV infection who presented with rapidly progressive glomerulonephritis and lung vasculitis. METHOD Case report presentation. RESULTS A 43-year-old male presented with fatigue, nausea and decreased urinary output of 3–4 days. Vital signs were stable and physical examination showed abdominal distention and peripheral oedema. His past medical history included heroin abuse. However, he denied any illicit drug use, and he had been on methadone maintenance treatment for 8 years. The patient was diagnosed with HIV 11 years previously. His antiretroviral therapy included abacavir, dolutegravir and lamivudine. CD4 count before admission was 180–200 cells/mm3. In addition to HIV infection, the patient had HCV diagnosed 20 years ago, but he has not received any treatment. The laboratory tests revealed pancytopenia (leukocytes 1.3 × 109/L, haemoglobin 66 g/L, platelets 66 × 109/L), kidney injury (proteinuria 0.8 g/24 h and haematuria) with renal insufficiency (creatinine 727 mcmol/L, urea 36.6 mmol/L). Ultrasound workup demonstrated diffuse changes in liver parenchyma with signs of portal hypertension, and normal-sized, non-obstructed kidneys with Grade 0 parenchymal echogenicity. Chest CT revealed wide areas of ground-glass opacity with patchy airspace consolidations, more severe in the left upper lobe. A serologic workup was positive for cryoglobulins, ANA, c-ANCA (high titre of anti-PR3 143 IU/mL), with decreased levels of C3 and C4. CRP level was slightly elevated (40 mg/L). Moreover patient had positive treponemal and non-treponemal syphilis serological tests. An ultrasound-guided renal biopsy showed crescentic glomerulonephritis with predominant IgM and focal C3, C1q deposition in glomerular capillary walls without any significant glomerular proliferative features. Changes could be interpreted as an immune complex and/or cryoglobulin-mediated glomerulonephritis, but overlapping pauci-immune glomerulonephritis could not be ruled out. Haemodialysis was initiated due to kidney failure and hyperhydration. The patient was treated with pulse methylprednisolone followed by a tapering course of oral prednisolone. Rituximab 1000 mg was prescribed after excluding HIV opportunistic infections, and treatment of syphilis with three doses of benzathine penicillin was used. Due to low GFR, HIV treatment was switched to Dolutegravir/Rilpivirine. The patient refused to initiate HCV therapy. The patient responded well to treatment and lung vasculitis and kidney function improved, therefore haemodialysis was discontinued. Serum creatinine level decreased to 130–120 mcmol/L and remained stable after 18 weeks since the treatment. CONCLUSION PRS in a patient with chronic infections, positive cryoglobulins and positive c-ANCA clinically seems more applicable to c-ANCA vasculitis than to cryoglobulinemic vasculitis. Still overlapping of both diseases could not be excluded.