Инсулинска резистенција и метаболичен синдром кај хепатитис Ц вирус серонегативни хероински зависници

Initial studies on impaired glucose-insulin homeostasis in heroin dependents have not defined the impact of concomitant hepatitis C infection (HCV), which has been  strongly associated with the development of insulin resistanceand metabolic syndrome (MS). The aim of our study was to evaluate the association of heroin dependence with glucose-insulin homeostasis and MS in heroin dependents with HCV seronegativity. Materials and methods: The study was prospective and cross-sectional, including 160 heroin dependents compared to a control group of 60 participants.MS was diagnosed using International Diabetes Federation criteria. The homeostatic model assessment for insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-%B) were used for assessing insulin resistance and β-cell function of pancreas. Results: MS was detected in 9.32% of heroin addicts. Heroin dependents with MS compared to dependents without MS were older, had higher BMI, waist circumference and significantly higher systolic and diastolic blood pressure, increased triglycerides (F=8.233, df=2, p<0.001), apoB (F=8.154, df=2, p=0.001), and reduced HDL-C (F=25.926, df=2, p<0.001) and apoA-I (F=16.406, df=2, p<0.001), significantly increased inuslinemia (F=4.928, df=2, p<0.05), insulin resistance-HOMA-IR (F=4,928, df=2, p<0,05) and insignificantly increased pancreatic β-cell function (194.66 ±224.05) (F=2.461, df=2, p>0.05). Conclusions: Insulin resistance and МS, independent of HCV, was also registered in heroin dependence. Timely recognition will enable more successful treatment of comorbidities and illicit drug dependence.Првичните студии за нарушена глукозно-инсулинска хомеостаза кај хероински зависници не го дефинираа и влијанието на  хепатитис Ц инфекцијата (ХЦВ), којa е силно поврзана со развој на инсулинска резистенција и метаболичен синдром (МС). Целта на нашата студија беше да ја процени поврзаноста на зависноста од хероин со глукозно-инсулинската хомеостаза и МС кај хероински зависници кои се ХЦВ серонегативни. Материјали и методи: Студијата беше проспективна и пресечна, вклучувајќи 160 хероински зависници и контролна група од 60 испитаници. МС беше дијагностициран според критериумите на Меѓународната федерација за дијабетес. За проценка на инсулинската резистенција и функцијата на β-клетките на панкреасот беше користен хомеостатскиот модел за инсулинска резистенција (HOMA-IR) и функцијата на β-клетките на панкреасот (HOMA-%B). Резултати: МС беше детектиран кај 9,32% од хероинските зависници и тие во споредба со зависниците без МС беа постари, со повисок БМИ, обем на половината и значително повисок систолен и дијастолен крвен притисок, покачени триглицериди (F=8, 233, df=2, p<0,001), apoB (F=8,154, df=2, p=0,001), и намалени HDL-C (F=25,926, df=2, p<0,001) и apoA-I (F=16,406, df=2, p<0,001), со значително зголемена инсулинемија (F=4,928, df =2, p<0,05), инсулинска резистенција – HOMA-IR (F=4,928, df=2, p<0,05) и незначително зголемена функција на β-клетките на панкреасот (194,66 ±224,05) (F=2,461, df=2, p>0,05). Заклучок: Инсулинската резистенција и МС, независно од ХЦВ инфекција, се регистрира и кај хероинската зависност. Навременото препознавање ќе овозможи поуспешен третман на коморбидитетите и на болеста на зависноста од илегални дроги

Insulin resistance and metabolic syndrome in hepatitis C virus seronegative heroin dependents

Initial studies on impaired glucose-insulin homeostasis in heroin dependents have not defined the impact of concomitant hepatitis C infection (HCV), which has been strongly associated with the development of insulin resistance and metabolic syndrome (MS). The aim of our study was to evaluate the association of heroin dependence with glucose-insulin homeostasis disturbances and MS in heroin dependents with HCV seronegativity. Materials and methods: The study was prospective and cross-sectional, including 160 heroin dependents compared to a control group of 60 participants. MS was diagnosed using International Diabetes Federation criteria. The homeostatic model assessment for insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-%B) were used for assessing insulin resistance and β-cell function of pancreas. Results: MS was detected in 9.32% of heroin addicts. Heroin dependents with MS compared to dependents without MS were older, had higher BMI, waist circumference and significantly higher systolic and diastolic blood pressure, increased triglycerides (F=8.233, df=2, p0.05). Conclusions: Insulin resistance and МS, independent of HCV, was also registered in heroin dependence. Timely recognition will enable more successful treatment of comorbidities and illicit drug dependenc

Non-Opioid Substances Acute Poisonings with Suicidal Intent in Patients with Opioid Use Disorder

Introduction: Several epidemiological studies have evaluated the role of illicit drug use in suicide behaviour. Aim: To assess patients with opioid use disorder and suicidal intent related to behavior, severity of acute poisoning and the most commonly used non-opioid substances. Materials and methods: This cross sectional study included 67 patients diagnosed with opioid use disorder. The study was conducted at the University Clinic of Toxicology in Skopje over a 5-year period (2013-2017). The following variables were examined: gender, age, duration and route of opioid administration, duration of hospitalization, and types of substances used in acute poisoning. Assessment of patients’ behavior and severity of poisoning was made by using the Suicide Behaviours Questionnaire-Revised and the Poison severity score. Results: The majority of patients were male (88.1%). The mean age of patients was 30±6.1 years. The average duration of opioid use disorder was 8.5±3.9. A single poisoning was found in 62.7%, double poisoning in 25.4%, and triple poisoning in 11.9% of participants. Benzodiazepines were most commonly used by the patients (55.2%). The largest number of patients (32.8%) had minor Poison severity score (PSS), and only 17.9% had severe PSS. None of the patients had a fatal suicide attempt. 86.6% of patients had a score of ≥7 indicating a high risk of repeat suicide attempts. Conclusion: Benzodiazepines were most commonly used as a single or combined substance in patients with opioid use disorder. PSS indicated that most of the participants were with minor PSS and with high risk of a repeat suicide attempt

Acute venlafaxine overdose with positive urine immunoassay for tramadol – clinical and diagnostic overlap - case report and literature overview

Objective. The overlapping of pharmacokinetics and/or the pharmacodynamics of medicines causes the occurrence of overlapping clinical syndromes and diagnostic issues, potentiated in overdoses. We report a case of severe venlafaxine poisoning where the clinical presentation and the results of rapid immunoassay test overlapped with tramadol intoxication. Case presentation. An unconscious women with recurrent seizers, hypertension and supposed acute medication poisoning in suicidal attempt was transported to our clinic. Previously, she had been lavaged, rehydrated and treated with 20 mg diazepam iv, 40 mg furosemide at the local general hospital. Her regular tablet therapy consisted of losartan, levothyroxine, venlafaxine, occasionally tramadol. At admission she was comatose, with isochoric normal pupils, BP 130/80 mm Hg, SaO2 86%, and recurrent episodes of seizures treated with 10mg diazepam iv, ocular clonus, hypertonus, temperature 38.9C, diaphoresis, facial hyperaemia, dark coloured urine, hyponatremia and rhabdomyolisis. The lateral flow immunoassay (AbuGnostR) was positive for tramadol, but the homogeneous enzyme immunoassay did not confirm it. After 36 hours of intensive treatment she became somnolent and reported ingestion of 2250 mg tbl Venlafaxine. The AbuGnost R test detects tramadol at cut off urine values 200ng/ml, but present cross reactivity with O-desmethyl-venlafaxine at cut off values up to 25000ng/ml. The following days she complained of muscular weakness, headaches and cognitive impairment, which lasted for more then one month after release from hospital. Conclusion. High concentrations of venlafaxine metabolites induce false positive tramadol immunoassay (AbuGnostR) test. Overlapping clinical presentations and metabolic pathways of venlafaxine and tramadol should alert physicians when interpret rapid immunoassay test. The mandatory principle when making medical decisions should cover synthesis of critically interpreted toxicology analysis, interview data and clinical features of the poisoning, which may help to avoid misleading conclusions and improve the diagnostic and therapy decisions

Non-Opioid Substances Acute Poisonings with Suicidal Intent in Patients with Opioid Use Disorder

Introduction: Several epidemiological studies have evaluated the role of illicit drug use in suicide behaviour. Aim: To assess patients with opioid use disorder and suicidal intent related to behavior, severity of acute poisoning and the most commonly used non-opioid substances. Materials and methods: This cross sectional study included 67 patients diagnosed with opioid use disorder. The study was conducted at the University Clinic of Toxicology in Skopje over a 5-year period (2013-2017). The following variables were examined: gender, age, duration and route of opioid administration, duration of hospitalization, and types of substances used in acute poisoning. Assessment of patients’ behavior and severity of poisoning was made by using the Suicide Behaviours Questionnaire-Revised and the Poison severity score. Results: The majority of patients were male (88.1%). The mean age of patients was 30±6.1 years. The average duration of opioid use disorder was 8.5±3.9. A single poisoning was found in 62.7%, double poisoning in 25.4%, and triple poisoning in 11.9% of participants. Benzodiazepines were most commonly used by the patients (55.2%). The largest number of patients (32.8%) had minor Poison severity score (PSS), and only 17.9% had severe PSS. None of the patients had a fatal suicide attempt. 86.6% of patients had a score of ≥7 indicating a high risk of repeat suicide attempts. Conclusion: Benzodiazepines were most commonly used as a single or combined substance in patients with opioid use disorder. PSS indicated that most of the participants were with minor PSS and with high risk of a repeat suicide attempt

Acute venlafaxine overdose with positive urine immunoassay for tramadol – clinical and diagnostic overlap - case report and literature overview

The overlapping of pharmacokinetics and/or the pharmacodynamics of medicines causes the occurrence of overlapping clinical syndromes and diagnostic issues, potentiated in overdoses. We report a case of severe venlafaxine poisoning where the clinical presentation and the results of rapid immunoassay test overlapped with tramadol intoxication. Case presentation. An unconscious women with recurrent seizers, hypertension and supposed acute medication poisoning in suicidal attempt was transported to our clinic. Previously, she had been lavaged, rehydrated and treated with 20 mg diazepam iv, 40 mg furosemide at the local general hospital. Her regular tablet therapy consisted of losartan, levothyroxine, venlafaxine, occasionally tramadol. At admission she was comatose, with isochoric normal pupils, BP 130/80 mm Hg, SaO2 86%, and recurrent episodes of seizures treated with 10mg diazepam iv, ocular clonus, hypertonus, temperature 38.9C, diaphoresis, facial hyperaemia, dark coloured urine, hyponatremia and rhabdomyolisis. The lateral flow immunoassay (AbuGnostR) was positive for tramadol, but the homogeneous enzyme immunoassay did not confirm it. After 36 hours of intensive treatment she became somnolent and reported ingestion of 2250 mg tbl Venlafaxine. The AbuGnost R test detects tramadol at cut off urine values 200ng/ml, but present cross reactivity with O-desmethyl-venlafaxine at cut off values up to 25000ng/ml. The following days she complained of muscular weakness, headaches and cognitive impairment, which lasted for more then one month after release from hospital. Conclusion. High concentrations of venlafaxine metabolites induce false positive tramadol immunoassay (AbuGnostR) test. Overlapping clinical presentations and metabolic pathways of venlafaxine and tramadol should alert physicians when interpret rapid immunoassay test. The mandatory principle when making medical decisions should cover synthesis of critically interpreted toxicology analysis, interview data and clinical features of the poisoning, which may help to avoid misleading conclusions and improve the diagnostic and therapy decisions

The role of urgent esophagogastoduodenoscopy in prognosis of acute caustic poisonings

Acute corrosive poisonings cause severe chemical injuries of the upper gastrointestinal tract, the most common location being the esophagus and the stomach. There are different opinions concerning the ques- tion of taking food and liquids by mouth immediately after caustic ingestion. This prospective study comprised 146 patients aged between 14 and 75 years divided in two groups. In the examined group prevailed those with esopha- gitis gr.IIb ( n=36; 54,54 %), esophagitis gr.III ( n=30; 45,45 %), gastritis gr. IIb (n=42, 63,63 %) and gastritis III (n=24;36,36%). In the controlled group prevailed those with esophagitis gr III ( n= 52; 65 %) and esophagitis gr IIb (n= 28; 35 %), gastritis gr. IIb( n= 55; 68,75 %)and gastritis gr III (n= 25; 31,25 %). Analysis of the results has shown a high percentage of esophageal stenosis in both groups 25 days after poisoning (31.82% v.s 43.75%), three and six months after poisoning (36.36% v.s. 52.50%) and also gastric injuries 25 days after the poisoning ( 37,88 % v.s. 46,25 %), three and six months after the poisoning (40,91% v.s 53,75%) In spite of the not significant difference, the results of our investigation have shown that the group with “esophageal rest” (NPO) had a smaller percentage of post-corrosive complications than the patients who were given food or liquids immediately after poisoning

Program of the University Clinic of Toxicology, Skopje, Republic of Macedonia in Treatment of Drug Addiction (Buprenorfin Treatment Protocol)

The program of our Clinic includes, not only treatment of acute intoxication with opioids and other drugs, but also comprehends clinical investigations and treatment of the somatic complications of this population. For the first time in our country our Clinic offers to this population the alternative way of treatment with Buprenorfin. The Clinic started with this protocol on August 1, 2009. During a period of two years, the treatment with Buprenorfine has been initiated in 353 patients, of which 211 regularly attend the medical check ups. This model is used according to the national clinical guidelines and procedures for the use of buprenorfine in the treatment of opioid dependence The dose of this medicament depends on the evolution of the withdrawal symptoms. We have used the objective and subjective opioid withdrawal scale for the observation of these symptoms (OOWS ; SOWS – Handelsman et al 1987). This protocol starts with a complete clinical investigations, (i.e. where all patients undergo the inclusion and exclusion criteria with a written consent). Afterwards, the patients are hospitalized and start with a Buprenorfin teratment. After period of 7-10 days hospitalization they come to our Clinic, like outpatients for a regular controls. We have precise evidence for every patient who comes for control (e.g. medical record with all biochemical and toxicological screenings). All patients are recommended a tight cooperation with psychiatrists who are specialized to treat the problematic drug addictions

Comparison of rhabdomyolysis in acutely intoxicated patients with psychotropic and chemical substances

Introduction: Rhabdomyolysis is characterized by a muscle injury that leads to the release of intracellular muscle contents/constituents into the systemic circulation. Aim: We examined the association between the severity of the clinical presentation and creatinine phosphokinase values in patients with rhabdomyolysis acutely intoxicated with psychotropic and chemical substances. Materials and methods: This clinically controlled prospective study included 140 patients with rhabdomyolysis hospitalized at the University Clinic of Toxicology in 2019. They were divided into two groups by the substance used for intoxication (psychotropic or chemical). Results: On the third day of hospitalization, we found a significant association between the type of intoxication and the degree of rhabdomyolysis according to the poisoning severity score (p=0.0256). The significance was due to intoxications with neuroleptics – 50% (n=6), anticonvulsants – 20% (n=1), antidepressants – 16.67% (n=2), heroin – 25% (n=1), and methadone – 54% (n=6). According to the poisoning severity score, the majority of intoxicated patients with chemical substances – other gases 100% (n=1), and those intoxicated with psychotropic substances – methadone 46.67% (n=7), neuroleptics 42.67% (n=5), heroin 40% (n=2), antidepressants 8.33% (n=1), had severe rhabdomyolysis. In psychotropic intoxications, creatine kinase had a significant linear positive weak correlation with mortality (p=0.0234). Conclusions: Rhabdomyolysis and its clinical symptoms and signs were significantly more common in patients intoxicated with psychotropic substances compared to chemical intoxications. Intoxicated patients with psychotropic substances had more severe rhabdomyolysis on the third day of hospitalization. In psychotropic intoxication, with increasing creatine kinase level on the first day there was a significant increase in mortality