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Suicides and suicide attempts by antidepressant drug poisonings reported in Costa Rica from 2007 to 2014
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Abstracts / Toxicology Letters 259S (2016) S73–S247
PO12.4 Intentional poisonings: Report from the Catholic University Poison Information Center 2006–2015
and finally, in 2015 the reported drug-related intoxications were 30 from 237 cases reported by the Laboratory of Toxicology of the Department of Toxicology of the University of San Carlos of Guatemala. Conclusions: Over the years, the number of intoxications reported by the Department of Toxicology is increasing, as well as the number of intoxications related to drugs of abuse.
C. Reinike 1 , L. Silva 1 , P. Cerda 1 , J.J. Mieres 1 , J.M. Del Campo 1 , E. Paris 1 , J.C. Ríos 1,2
http://dx.doi.org/10.1016/j.toxlet.2016.07.593
1
PO12.3 Incidence of hypersensitivity reactions following copperhead snakebites treated with Fab AV or placebo M.E. Mullins 1 , C.J. Gerardo 2 , E.J. Lavonas 3 , for the Copperhead Envenomation Study Group12 1
Emergency Medicine, Washington University, St. Louis, MO, USA Emergency Medicine, Duke University, Durham, NC, USA 3 Rocky Mountain Poison and Drug Center, Denver, CO, USA 2
Introduction: Risk of adverse reactions to antivenom is a concern for many clinicians. A meta-analysis of patients given ovine-derived Crotalidae polyvalent immune Fab AV (CroFab® , BTG International) conservatively attributed all reactions to the antivenom and estimated immediate hypersensitivity reactions or serum sickness were 8% and 13%, respectively. The comparative incidence of reactions between patients with snakebites of similar severities treated with FabAV or no antivenom remains unknown. Objective: To compare the incidence of hypersensitivity reactions following copperhead envenomation treated with FabAV or placebo. Materials and methods: Patients with copperhead snakebites received treatment and follow-up in a prospective, multicenter, randomized, controlled trial of Fab AV or placebo (ClinicalTrials.gov Identifier NCT01864200). The treatment allocation ratio Fab AV:placebo was 2:1. All patients had 24 h of observation with follow-up at 0, 3, 7, 14, 21, and 28 d from discharge. We included all patients who had at least 1 dose of study treatment. We reviewed all treatment-emergent adverse events (TEAEs). We used a previously published scale to classify likely hypersensitivity reactions as mild (skin, subcutaneous tissues only), moderate (respiratory, cardiovascular or gastrointestinal), or severe (hypoxia, hypotension, or neurological compromise). Results: Out of 74 patients (39 M, 35 F) at 12 sites, 45 patients (23 M, 22 F) received FabAV and 29 patients (16 M, 13 F) received placebo. Five of 45 Fab AV patients and 4 of 29 placebo patients had moderate envenomation; all others were mild. There were 25 FabAV patients and 8 placebo patients who had ≥1 TEAE. Mild skin reactions occurred in 11/45 FabAV patients and 1/29 placebo patients. Moderate GI TEAEs occurred in 7/45 FabAV patients and 2/29 of placebo patients. Respiratory TEAEs occurred in 3/45 of FabAV patients and 0 placebo patients. One patient in each group had Hypotension (severe reaction). Conclusions: The incidence of FabAV hypersensitivity reactions is low. Most reactions were mild skin reactions. Financial support: BTG. http://dx.doi.org/10.1016/j.toxlet.2016.07.594
Centro de Información Toxicológica, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile 2 Department of Clinical Laboratory, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile Introduction: According to figures from the World Health Organization (WHO), every year, one million people commit suicide worldwide, reaching 1.4% of world morbidity, being one of the leading causes of death in some countries. Suicide attempt by ingestion of toxic substances is a public health concern that requires urgent attention because of the serious consequences that these exposures can cause on health. These exposures include those with suicidal intent which have been increasing in recent years according to international statistics. Objective: The aim of this work was to describe epidemiologically cases involving intentional poisonings in Chilean population received by Centro de Información Toxicologica de la Universidad Católica (CITUC) during the 2006–2015 period. Materials and methods: A descriptive, retrospective study was conducted which included all intentional poisonings received by the center during the given period. The variables analyzed were age, sex, route of exposure, causal agent and interlocutor. Results: A total of 78,330 cases of intentional poisoning (29% of the total cases) were received. Of these, 93% were suicide attempts which involved mainly women (76%), in the adults and adolescents groups (43% and 19%, respectively). The main agent involved were pharmaceuticals products (87%), specially those acting at central nervous system level (27% and 26% antidepressants and anxiolytics, respectively). Females had a 3.3 times higher risk for suicide than males (OR: 3.3; CI95% : 3.2–3.4; p < 0.001). It was noted that between 2006 and 2015 the incidence of suicide attempts increased from 23% to 28%. Conclusions: Intentional poisoning represents a public health concern in Chile. The highest percentage of cases corresponds to suicide attempts. Pharmaceutical products were the main cause specially those active at central nervous system level the main risk group was females. http://dx.doi.org/10.1016/j.toxlet.2016.07.595 PP12.1 Suicides and suicide attempts by antidepressant drug poisonings reported in Costa Rica from 2007 to 2014 M.M. Castillo-Guerrero 1 , M. Gómez-Vargas 1 , B. Scarpa 2 , F. Arias-Mora 1 1 Department of Pharmacology, Toxicology and Pharmacodependence Universidad de Costa Rica, San José, Costa Rica 2 Department of Statistical Sciences, University of Padua, Padua, Italy
Introduction: According to information from the World Health Organization, more than 800,000 people in the world die each year from suicide and many more make suicide attempts. 2012 data, place suicide as the second leading cause of death worldwide among the population aged 15–29 years old. According to the PanAmerican Health Organization, in Central America there has been
Abstracts / Toxicology Letters 259S (2016) S73–S247
an increase in suicide rates. Medications are the main causes of poisoning in Costa Rica, followed by pesticides. Antidepressants are one of the main groups of drugs related to poisonings. Objective: This work aims to analyze the suicides and suicide attempts between 2007 and 2014 in Costa Rica. Materials and methods: Assessment of the protocols was conducted by means of a tabular database as to the following criteria: province, canton, gender, age, type of antidepressant, and type of intoxication. For statistical analysis, a logistic regression analysis was conducted to determine the probability of a person to die because of a suicide attempt by antidepressant drug poisoning. Results: Most cases of poisoning with antidepressant drugs were caused by suicide attempts. Selective serotonin reuptake inhibitors antidepressants (SSRIs) were reported in 1156 cases (52%) of suicide attempts by antidepressant drug poisonings in Costa Rica from 2007 to 2014. The highest number of suicide attempts occurred in females between 15 and 29 years old. Most deaths occurred similarly in women, but mainly in the age range of 30–44 years old. There is a higher probability of committing suicide with an SSRI antidepressant poisoning given all other relevant variables, than with other types of antidepressants. The probability of suicide by poisoning with antidepressants given all other relevant variables, is higher in males than in females. Furthermore, given all other variables, the likelihood of suicide increases with age. Conclusions: It was found that men have a higher probability of dying from a suicide attempt by antidepressant drug poisoning. The risk of dying from a suicide attempt by antidepressant drug poisoning increases with age and it tends to be lower if the poisoning occurs with an antidepressant of the selective serotonin reuptake inhibitors (SSRIs) type. Financial support: Universidad de Costa Rica, Costa Rica. http://dx.doi.org/10.1016/j.toxlet.2016.07.596 PP12.2 Reduced exposure to harmful and potentially harmful constituents after 90 days of use of tobacco heating system 2.2 in Japan: A comparison with continued combustible cigarette use or smoking abstinence P. Picavet 1 , C. Haziza 1 , N. Lama 1 , A. Donelli 1 , G. Baker 1 , J. Ancerewicz 1 , M. Benzimra 1 , Franzon M 1 , M.D. Masahiro Endo 2 , F. Lüdicke 1 1 2
Philip Morris International R&D, Neuchatel, Switzerland Osaki Hospital Tokyo Heart Center, Tokyo, Japan
Introduction: This study is part of a clinical program to assess the Tobacco Heating System (THS), a candidate modified risk tobacco product. Objective: The study was designed to assess exposure reduction to selected harmful and potentially harmful constituents (HPHC) after 5 days of ad libitum use of THS 2.2 menthol (mTHS) in confinement and 85 days in an ambulatory setting compared to continued smoking of conventional menthol cigarettes (mCC) and smoking abstinence (SA). Materials and methods: Biomarkers of exposure (BoExp) to sixteen HPHCs were evaluated and selected Clinical Risk Endpoints (CRE) were monitored. Twenty-four hour urine and blood samples were collected to evaluate levels of BoExp and CRE using validated analytical methods. Results: After 2 days of baseline (BL) (mCC), 160 healthy smokers, aged 23 to 65 years, were randomized to continue to smoke mCC (n = 40), to switch to mTHS (n = 80), or to stop smoking (n = 40)
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for 90 days in this open-label, randomized, controlled, 3-arm parallel group study. The study was conducted in Japan according to GCP and is registered in ClinicalTrials.gov (NCT01970995). The average daily product use was stable in the mTHS arm (BL = 13.1 mCC; Day 90 = 12.7 mTHS) and slightly increased in the mCC arm (BL = 12.5 mCC; Day 90 = 15.2 mCC) over the exposure period. Nicotine exposure measured as nicotine equivalents were comparable in both arms (mTHS:mCC ratio of 104% [95% CI: 66, 163]). The levels of BoExp, except S-BMA, were significantly reduced at Day 5 in the mTHS arm compared to mCC, approaching results obtained in the SA arm and were sustained throughout the exposure period (Day 5: −49% to −94%; Day 90: −41% to −94%). Initial shifts of monitored CREs in the direction of SA were observed. Conclusions: mTHS showed significant, sustained reduction in exposure to HPHCs after 90 days of mTHS use, as compared to CC, approaching levels observed upon smoking abstinence. Initial favorable shifts of monitored CREs were observed. Financial support: Philip Morris Products S.A., Neuchâtel, Switzerland. http://dx.doi.org/10.1016/j.toxlet.2016.07.597 PP12.3 Sharing systems toxicology data for inhalation toxicology S. Boué 1 , B. Hardy 2 , W. Hayes 3 , V. Belcastro 1 , T. Exner 2 , J. Dokler 2 , J. Hoeng 1 , M.C. Peitsch 1 1
PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland Douglas Connect GmbH, Zeiningen, Switzerland 3 Selventa, 1 Alewife Center, Cambridge, MA, USA 2
Introduction: Large international programs (e.g., Tox21, ToxCast in USA; EUToxRisk, SEURAT in Europe, and TG-GATEs in Japan) increasingly generate large and complex toxicology-relevant data sets. These data sets are analyzed by the scientific community with the aim to develop new hypotheses, predictive models and testing strategies. Moreover, industrial R&D endeavors may generate even larger amounts of data but are not as proactive in the area of data sharing. Therefore, data and results sharing by industries represent a great opportunity for the scientific community as a whole. Data science is crucial in extracting mechanistic knowledge from these data sets, which are often generated with diverse methods and standards. It is therefore of utmost importance that the data sets and the methods used for their production are both traceable and well described. Objective: Develop a Systems Toxicology Data Repository for Tobacco Harm Reduction. Material and methods: Building on the experience gained by Douglas Connect during the OpenTox project (www.opentox.net), a proof of concept database and website (‘the SysTox Portal’) have been developed to share results from in vivo inhalation studies as well as in vitro studies conducted by Philip Morris International R&D that assess candidate Modified Risk Tobacco Products (MRTP). Data modeling took into account the latest standards in terms of data sharing and reproducible research. Results: The data and methods used to generate it have been curated and prepared in ISA-TAB format which are stored in a database that can be accessed via a “search portal” in the SysTox portal website. Moreover, the portal allows to browse the data either by study or by mechanism (e.g. inflammation, oxidative stress) and to get the relevant information related to study design, material and methods used, as well as a view of the most important results obtained in the study. The established infrastructure and standards used will be summarized in the poster.
Abstracts / Toxicology Letters 259S (2016) S73–S247
PO12.4 Intentional poisonings: Report from the Catholic University Poison Information Center 2006–2015
and finally, in 2015 the reported drug-related intoxications were 30 from 237 cases reported by the Laboratory of Toxicology of the Department of Toxicology of the University of San Carlos of Guatemala. Conclusions: Over the years, the number of intoxications reported by the Department of Toxicology is increasing, as well as the number of intoxications related to drugs of abuse.
C. Reinike 1 , L. Silva 1 , P. Cerda 1 , J.J. Mieres 1 , J.M. Del Campo 1 , E. Paris 1 , J.C. Ríos 1,2
http://dx.doi.org/10.1016/j.toxlet.2016.07.593
1
PO12.3 Incidence of hypersensitivity reactions following copperhead snakebites treated with Fab AV or placebo M.E. Mullins 1 , C.J. Gerardo 2 , E.J. Lavonas 3 , for the Copperhead Envenomation Study Group12 1
Emergency Medicine, Washington University, St. Louis, MO, USA Emergency Medicine, Duke University, Durham, NC, USA 3 Rocky Mountain Poison and Drug Center, Denver, CO, USA 2
Introduction: Risk of adverse reactions to antivenom is a concern for many clinicians. A meta-analysis of patients given ovine-derived Crotalidae polyvalent immune Fab AV (CroFab® , BTG International) conservatively attributed all reactions to the antivenom and estimated immediate hypersensitivity reactions or serum sickness were 8% and 13%, respectively. The comparative incidence of reactions between patients with snakebites of similar severities treated with FabAV or no antivenom remains unknown. Objective: To compare the incidence of hypersensitivity reactions following copperhead envenomation treated with FabAV or placebo. Materials and methods: Patients with copperhead snakebites received treatment and follow-up in a prospective, multicenter, randomized, controlled trial of Fab AV or placebo (ClinicalTrials.gov Identifier NCT01864200). The treatment allocation ratio Fab AV:placebo was 2:1. All patients had 24 h of observation with follow-up at 0, 3, 7, 14, 21, and 28 d from discharge. We included all patients who had at least 1 dose of study treatment. We reviewed all treatment-emergent adverse events (TEAEs). We used a previously published scale to classify likely hypersensitivity reactions as mild (skin, subcutaneous tissues only), moderate (respiratory, cardiovascular or gastrointestinal), or severe (hypoxia, hypotension, or neurological compromise). Results: Out of 74 patients (39 M, 35 F) at 12 sites, 45 patients (23 M, 22 F) received FabAV and 29 patients (16 M, 13 F) received placebo. Five of 45 Fab AV patients and 4 of 29 placebo patients had moderate envenomation; all others were mild. There were 25 FabAV patients and 8 placebo patients who had ≥1 TEAE. Mild skin reactions occurred in 11/45 FabAV patients and 1/29 placebo patients. Moderate GI TEAEs occurred in 7/45 FabAV patients and 2/29 of placebo patients. Respiratory TEAEs occurred in 3/45 of FabAV patients and 0 placebo patients. One patient in each group had Hypotension (severe reaction). Conclusions: The incidence of FabAV hypersensitivity reactions is low. Most reactions were mild skin reactions. Financial support: BTG. http://dx.doi.org/10.1016/j.toxlet.2016.07.594
Centro de Información Toxicológica, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile 2 Department of Clinical Laboratory, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile Introduction: According to figures from the World Health Organization (WHO), every year, one million people commit suicide worldwide, reaching 1.4% of world morbidity, being one of the leading causes of death in some countries. Suicide attempt by ingestion of toxic substances is a public health concern that requires urgent attention because of the serious consequences that these exposures can cause on health. These exposures include those with suicidal intent which have been increasing in recent years according to international statistics. Objective: The aim of this work was to describe epidemiologically cases involving intentional poisonings in Chilean population received by Centro de Información Toxicologica de la Universidad Católica (CITUC) during the 2006–2015 period. Materials and methods: A descriptive, retrospective study was conducted which included all intentional poisonings received by the center during the given period. The variables analyzed were age, sex, route of exposure, causal agent and interlocutor. Results: A total of 78,330 cases of intentional poisoning (29% of the total cases) were received. Of these, 93% were suicide attempts which involved mainly women (76%), in the adults and adolescents groups (43% and 19%, respectively). The main agent involved were pharmaceuticals products (87%), specially those acting at central nervous system level (27% and 26% antidepressants and anxiolytics, respectively). Females had a 3.3 times higher risk for suicide than males (OR: 3.3; CI95% : 3.2–3.4; p < 0.001). It was noted that between 2006 and 2015 the incidence of suicide attempts increased from 23% to 28%. Conclusions: Intentional poisoning represents a public health concern in Chile. The highest percentage of cases corresponds to suicide attempts. Pharmaceutical products were the main cause specially those active at central nervous system level the main risk group was females. http://dx.doi.org/10.1016/j.toxlet.2016.07.595 PP12.1 Suicides and suicide attempts by antidepressant drug poisonings reported in Costa Rica from 2007 to 2014 M.M. Castillo-Guerrero 1 , M. Gómez-Vargas 1 , B. Scarpa 2 , F. Arias-Mora 1 1 Department of Pharmacology, Toxicology and Pharmacodependence Universidad de Costa Rica, San José, Costa Rica 2 Department of Statistical Sciences, University of Padua, Padua, Italy
Introduction: According to information from the World Health Organization, more than 800,000 people in the world die each year from suicide and many more make suicide attempts. 2012 data, place suicide as the second leading cause of death worldwide among the population aged 15–29 years old. According to the PanAmerican Health Organization, in Central America there has been
Abstracts / Toxicology Letters 259S (2016) S73–S247
an increase in suicide rates. Medications are the main causes of poisoning in Costa Rica, followed by pesticides. Antidepressants are one of the main groups of drugs related to poisonings. Objective: This work aims to analyze the suicides and suicide attempts between 2007 and 2014 in Costa Rica. Materials and methods: Assessment of the protocols was conducted by means of a tabular database as to the following criteria: province, canton, gender, age, type of antidepressant, and type of intoxication. For statistical analysis, a logistic regression analysis was conducted to determine the probability of a person to die because of a suicide attempt by antidepressant drug poisoning. Results: Most cases of poisoning with antidepressant drugs were caused by suicide attempts. Selective serotonin reuptake inhibitors antidepressants (SSRIs) were reported in 1156 cases (52%) of suicide attempts by antidepressant drug poisonings in Costa Rica from 2007 to 2014. The highest number of suicide attempts occurred in females between 15 and 29 years old. Most deaths occurred similarly in women, but mainly in the age range of 30–44 years old. There is a higher probability of committing suicide with an SSRI antidepressant poisoning given all other relevant variables, than with other types of antidepressants. The probability of suicide by poisoning with antidepressants given all other relevant variables, is higher in males than in females. Furthermore, given all other variables, the likelihood of suicide increases with age. Conclusions: It was found that men have a higher probability of dying from a suicide attempt by antidepressant drug poisoning. The risk of dying from a suicide attempt by antidepressant drug poisoning increases with age and it tends to be lower if the poisoning occurs with an antidepressant of the selective serotonin reuptake inhibitors (SSRIs) type. Financial support: Universidad de Costa Rica, Costa Rica. http://dx.doi.org/10.1016/j.toxlet.2016.07.596 PP12.2 Reduced exposure to harmful and potentially harmful constituents after 90 days of use of tobacco heating system 2.2 in Japan: A comparison with continued combustible cigarette use or smoking abstinence P. Picavet 1 , C. Haziza 1 , N. Lama 1 , A. Donelli 1 , G. Baker 1 , J. Ancerewicz 1 , M. Benzimra 1 , Franzon M 1 , M.D. Masahiro Endo 2 , F. Lüdicke 1 1 2
Philip Morris International R&D, Neuchatel, Switzerland Osaki Hospital Tokyo Heart Center, Tokyo, Japan
Introduction: This study is part of a clinical program to assess the Tobacco Heating System (THS), a candidate modified risk tobacco product. Objective: The study was designed to assess exposure reduction to selected harmful and potentially harmful constituents (HPHC) after 5 days of ad libitum use of THS 2.2 menthol (mTHS) in confinement and 85 days in an ambulatory setting compared to continued smoking of conventional menthol cigarettes (mCC) and smoking abstinence (SA). Materials and methods: Biomarkers of exposure (BoExp) to sixteen HPHCs were evaluated and selected Clinical Risk Endpoints (CRE) were monitored. Twenty-four hour urine and blood samples were collected to evaluate levels of BoExp and CRE using validated analytical methods. Results: After 2 days of baseline (BL) (mCC), 160 healthy smokers, aged 23 to 65 years, were randomized to continue to smoke mCC (n = 40), to switch to mTHS (n = 80), or to stop smoking (n = 40)
S141
for 90 days in this open-label, randomized, controlled, 3-arm parallel group study. The study was conducted in Japan according to GCP and is registered in ClinicalTrials.gov (NCT01970995). The average daily product use was stable in the mTHS arm (BL = 13.1 mCC; Day 90 = 12.7 mTHS) and slightly increased in the mCC arm (BL = 12.5 mCC; Day 90 = 15.2 mCC) over the exposure period. Nicotine exposure measured as nicotine equivalents were comparable in both arms (mTHS:mCC ratio of 104% [95% CI: 66, 163]). The levels of BoExp, except S-BMA, were significantly reduced at Day 5 in the mTHS arm compared to mCC, approaching results obtained in the SA arm and were sustained throughout the exposure period (Day 5: −49% to −94%; Day 90: −41% to −94%). Initial shifts of monitored CREs in the direction of SA were observed. Conclusions: mTHS showed significant, sustained reduction in exposure to HPHCs after 90 days of mTHS use, as compared to CC, approaching levels observed upon smoking abstinence. Initial favorable shifts of monitored CREs were observed. Financial support: Philip Morris Products S.A., Neuchâtel, Switzerland. http://dx.doi.org/10.1016/j.toxlet.2016.07.597 PP12.3 Sharing systems toxicology data for inhalation toxicology S. Boué 1 , B. Hardy 2 , W. Hayes 3 , V. Belcastro 1 , T. Exner 2 , J. Dokler 2 , J. Hoeng 1 , M.C. Peitsch 1 1
PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland Douglas Connect GmbH, Zeiningen, Switzerland 3 Selventa, 1 Alewife Center, Cambridge, MA, USA 2
Introduction: Large international programs (e.g., Tox21, ToxCast in USA; EUToxRisk, SEURAT in Europe, and TG-GATEs in Japan) increasingly generate large and complex toxicology-relevant data sets. These data sets are analyzed by the scientific community with the aim to develop new hypotheses, predictive models and testing strategies. Moreover, industrial R&D endeavors may generate even larger amounts of data but are not as proactive in the area of data sharing. Therefore, data and results sharing by industries represent a great opportunity for the scientific community as a whole. Data science is crucial in extracting mechanistic knowledge from these data sets, which are often generated with diverse methods and standards. It is therefore of utmost importance that the data sets and the methods used for their production are both traceable and well described. Objective: Develop a Systems Toxicology Data Repository for Tobacco Harm Reduction. Material and methods: Building on the experience gained by Douglas Connect during the OpenTox project (www.opentox.net), a proof of concept database and website (‘the SysTox Portal’) have been developed to share results from in vivo inhalation studies as well as in vitro studies conducted by Philip Morris International R&D that assess candidate Modified Risk Tobacco Products (MRTP). Data modeling took into account the latest standards in terms of data sharing and reproducible research. Results: The data and methods used to generate it have been curated and prepared in ISA-TAB format which are stored in a database that can be accessed via a “search portal” in the SysTox portal website. Moreover, the portal allows to browse the data either by study or by mechanism (e.g. inflammation, oxidative stress) and to get the relevant information related to study design, material and methods used, as well as a view of the most important results obtained in the study. The established infrastructure and standards used will be summarized in the poster.