Publications by authors named "Knut E Hovda"

10 Publications

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Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

Clin Toxicol (Phila) 2021 Mar 16:1-13. Epub 2021 Mar 16.

Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.

Objective: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata.

Methods: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Descriptive data by age and sex are presented and compared among age/sex categories and among drug families.

Results: Of 17,371 patients were included during the 39-month period, 17,198 (99.0%) had taken at least one of the investigated drugs (median age: 31 years; 23.9% female; ethanol co-ingestion recorded in 41.5%, unknown in 31.2%; multiple drug use in 37.9%). Opioids (in 31.4% of patients) and amphetamines (23.3%) were the most frequently involved and hallucinogens (1.9%) and ketamine (1.7%) the least. Overall, female patients were younger than males, both in the whole cohort (median age 29 vs. 32 years;  < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years;  = 0.83). The relative proportion of each drug group was different at every age strata and some patterns could be clearly described: cannabis, NPS and hallucinogens were the most common in patients <20 years; amphetamines, ketamine and cocaine in the 20- to 39-year group; GHB/GBL in the 30- to 39-year group; and opioids and benzodiazepines in patients ≥40 years. Ethanol and other drug co-ingestion was more frequent at middle-ages, and multidrug co-ingestion was more common in females than males.

Conclusion: Differences in the drugs involved in acute drug toxicity presentations according to age and sex may be relevant for developing drug-prevention and education programs for some particular subgroups of the population based on the increased risk of adverse events in specific sex and/or age strata.
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http://dx.doi.org/10.1080/15563650.2021.1884693DOI Listing
March 2021

MDMA-related presentations to the emergency departments of the European Drug Emergencies Network plus (Euro-DEN Plus) over the four-year period 2014-2017.

Clin Toxicol (Phila) 2021 02 17;59(2):131-137. Epub 2020 Jul 17.

Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Context: 3,4-Methylenedioxymethamphetamine (MDMA) remains one of the most commonly used recreational drugs in Europe. Monitoring of Emergency Department (ED) presentations with acute toxicity associated with MDMA is important to determine trends in MDMA use and harms.

Methods: Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all ED presentations with acute toxicity involving MDMA use, alone or in combination with other substances, between 1 January 2014 and 31 December 2017. Geographical distribution, time trends, patient demographics, clinical features, management and outcome were analysed.

Results: Out of 23,947 presentations, 2013 (8.4%) involved MDMA, used alone (88, 4.4%) or with other substances (1925, 95.6%). The proportion of MDMA presentations varied by country, from over 15% in France to less than 5% in Norway. For the 15 sentinel centres where data were available for all four years, MDMA-related presentations peaked in 2016 (10.4% 8.1% in 2015,  < 0.0001), thereafter decreasing in 2017 (8.2%,  = 0.0002). 1436 (71.3%) presentations involved males. Females were significantly younger than males (median 23 years, interquartile range, IQR, 20-27 years, median 25 years, IQR 21-30 years,  < 0.0001). Compared to presentations of acute toxicity with lone-use cocaine, presentations with lone-use MDMA occurred more frequently during the weekend (58.0% 43.9%,  = 0.02), were more frequently medically discharged directly from the ED (74.7% 62.4%,  = 0.03), and less frequently received sedation (43.5% 66.5%,  = 0.003).

Conclusions: This large multicentre series of MDMA presentations to EDs showed geographical variation and changes in time trends and in patient demographics. Triangulation with data from complementary sources including seizures, prevalence of use and wastewater analysis, will enable a greater understanding of the public health implications of MDMA use in Europe.
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http://dx.doi.org/10.1080/15563650.2020.1784914DOI Listing
February 2021

Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas.

Emergencias 2018 Dic;30(6):385-394

Área de Urgencias, Hospital Clínic, Barcelona; Grupo de Investigación "Urgencias: Procesos y Patologías", IDIBAPS, Barcelona, España.

Objectives: To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe.

Material And Methods: Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe.

Results: A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe.

Conclusion: The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition.
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July 2019

Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse.

Toxicol Lett 2017 Aug 1;277:84-91. Epub 2017 Jun 1.

Department of Clinical Toxicology, Klinikum rechts der Isar, Technical University of Munich, Germany.

Objective: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse.

Method: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes.

Results: We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01).

Conclusions: The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse.
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http://dx.doi.org/10.1016/j.toxlet.2017.05.030DOI Listing
August 2017

Five-year mortality after acute poisoning treated in ambulances, an emergency outpatient clinic and hospitals in Oslo.

Scand J Trauma Resusc Emerg Med 2013 Aug 21;21:65. Epub 2013 Aug 21.

Department of Acute Medicine, Oslo University Hospital Ullevaal, Kirkeveien 166, Oslo 0450, Norway.

Background: The long-term mortality after prehospital treatment for acute poisoning has not been studied previously. Thus, we aimed to estimate the five-year mortality and examine the causes of death and predictors of death for all acutely poisoned patients treated in ambulances, the emergency outpatient clinic, and hospitals in Oslo during 2003-2004.

Methods: A prospective cohort study included all adults (≥16 years; n=2045, median age=35 years, male=58%) who were discharged after treatment for acute poisoning in ambulances, the emergency outpatient clinic, and the four hospitals in Oslo during one year. The patients were observed until the end of 2008. Standardized mortality rates (SMRs) were calculated and multivariate Cox regression analysis was applied.

Results: The study comprised 2045 patients; 686 treated in ambulances, 646 treated in the outpatient clinic, and 713 treated in hospitals. After five years, 285 (14%) patients had died (four within one week). The SMRs after ambulance, outpatient, and hospital treatment were 12 (CI 9-14), 10 (CI 8-12), and 6 (CI 5-7), respectively. The overall SMR was 9 (CI 8-10), while the SMR after opioid poisoning was 27 (CI 21-32). The most frequent cause of death was accidents (38%). In the regression analysis, opioids as the main toxic agents (HR 2.3, CI 1.6-3.0), older age (HR 1.6, CI 1.5-1.7), and male sex (HR 1.4, CI 1.1-1.9) predicted death, whereas the treatment level did not predict death.

Conclusions: The patients had high mortality compared with the general population. Those treated in hospital had the lowest mortality. Opioids were the major predictor of death.
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http://dx.doi.org/10.1186/1757-7241-21-65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846782PMC
August 2013

Outpatient treatment of acute poisonings in Oslo: poisoning pattern, factors associated with hospitalization, and mortality.

Scand J Trauma Resusc Emerg Med 2012 Jan 4;20. Epub 2012 Jan 4.

Department of Acute Medicine, Oslo University Hospital Ullevaal, Norway.

Background: Most patients with acute poisoning are treated as outpatients worldwide. In Oslo, these patients are treated in a physician-led outpatient clinic with limited diagnostic and treatment resources, which reduces both the costs and emergency department overcrowding. We describe the poisoning patterns, treatment, mortality, factors associated with hospitalization and follow-up at this Emergency Medical Agency (EMA, "Oslo Legevakt"), and we evaluate the safety of this current practice.

Methods: All acute poisonings in adults (> or = 16 years) treated at the EMA during one year (April 2008 to April 2009) were included consecutively in an observational study design. The treating physicians completed a standardized form comprising information needed to address the study's aims. Multivariate logistic regression analysis was used to identify the factors associated with hospitalization.

Results: There were 2348 contacts for 1856 individuals; 1157 (62%) were male, and the median age was 34 years. The most frequent main toxic agents were ethanol (43%), opioids (22%) and CO or fire smoke (10%). The physicians classified 73% as accidental overdoses with substances of abuse taken for recreational purposes, 15% as other accidents (self-inflicted or other) and 11% as suicide attempts. Most (91%) patients were treated with observation only. The median observation time until discharge was 3.8 hours. No patient developed sequelae or died at the EMA. Seventeen per cent were hospitalized. Gamma-hydroxybutyric acid, respiratory depression, paracetamol, reduced consciousness and suicidal intention were factors associated with hospitalization. Forty-eight per cent were discharged without referral to follow-up. The one-month mortality was 0.6%. Of the nine deaths, five were by new accidental overdose with substances of abuse.

Conclusions: More than twice as many patients were treated at the EMA compared with all hospitals in Oslo. Despite more than a doubling of the annual number of poisoned patients treated at the EMA since 2003, there was no mortality or sequelae, indicating that the current practice is safe. Thus, most low- to intermediate-acuity poisonings can be treated safely without the need to access hospital resources. Although the short-term mortality was low, more follow-up of patients with substance abuse should be encouraged.
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http://dx.doi.org/10.1186/1757-7241-20-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285081PMC
January 2012

Outpatient treatment of acute poisonings in Oslo: poisoning pattern, factors associated with hospitalization, and mortality.

Scand J Trauma Resusc Emerg Med 2012 Jan 4;20. Epub 2012 Jan 4.

Department of Acute Medicine, Oslo University Hospital Ullevaal, Norway.

Background: Most patients with acute poisoning are treated as outpatients worldwide. In Oslo, these patients are treated in a physician-led outpatient clinic with limited diagnostic and treatment resources, which reduces both the costs and emergency department overcrowding. We describe the poisoning patterns, treatment, mortality, factors associated with hospitalization and follow-up at this Emergency Medical Agency (EMA, "Oslo Legevakt"), and we evaluate the safety of this current practice.

Methods: All acute poisonings in adults (> or = 16 years) treated at the EMA during one year (April 2008 to April 2009) were included consecutively in an observational study design. The treating physicians completed a standardized form comprising information needed to address the study's aims. Multivariate logistic regression analysis was used to identify the factors associated with hospitalization.

Results: There were 2348 contacts for 1856 individuals; 1157 (62%) were male, and the median age was 34 years. The most frequent main toxic agents were ethanol (43%), opioids (22%) and CO or fire smoke (10%). The physicians classified 73% as accidental overdoses with substances of abuse taken for recreational purposes, 15% as other accidents (self-inflicted or other) and 11% as suicide attempts. Most (91%) patients were treated with observation only. The median observation time until discharge was 3.8 hours. No patient developed sequelae or died at the EMA. Seventeen per cent were hospitalized. Gamma-hydroxybutyric acid, respiratory depression, paracetamol, reduced consciousness and suicidal intention were factors associated with hospitalization. Forty-eight per cent were discharged without referral to follow-up. The one-month mortality was 0.6%. Of the nine deaths, five were by new accidental overdose with substances of abuse.

Conclusions: More than twice as many patients were treated at the EMA compared with all hospitals in Oslo. Despite more than a doubling of the annual number of poisoned patients treated at the EMA since 2003, there was no mortality or sequelae, indicating that the current practice is safe. Thus, most low- to intermediate-acuity poisonings can be treated safely without the need to access hospital resources. Although the short-term mortality was low, more follow-up of patients with substance abuse should be encouraged.
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http://dx.doi.org/10.1186/1757-7241-20-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285081PMC
January 2012

Fatal poisonings in Oslo: a one-year observational study.

BMC Emerg Med 2010 Jun 6;10:13. Epub 2010 Jun 6.

Department of Acute Medicine, Oslo University Hospital Ulleval, Kirkeveien 166, N-0407 Oslo, Norway.

Background: Acute poisonings are common and are treated at different levels of the health care system. Since most fatal poisonings occur outside hospital, these must be included when studying characteristics of such deaths. The pattern of toxic agents differs between fatal and non-fatal poisonings. By including all poisoning episodes, cause-fatality rates can be calculated.

Methods: Fatal and non-fatal acute poisonings in subjects aged > or =16 years in Oslo (428 198 inhabitants) were included consecutively in an observational multi-centre study including the ambulance services, the Oslo Emergency Ward (outpatient clinic), and hospitals, as well as medico-legal autopsies from 1st April 2003 to 31st March 2004. Characteristics of fatal poisonings were examined, and a comparison of toxic agents was made between fatal and non-fatal acute poisoning.

Results: In Oslo, during the one-year period studied, 103 subjects aged > or =16 years died of acute poisoning. The annual mortality rate was 24 per 100 000. The male-female ratio was 2:1, and the mean age was 44 years (range 19-86 years). In 92 cases (89%), death occurred outside hospital. The main toxic agents were opiates or opioids (65% of cases), followed by ethanol (9%), tricyclic anti-depressants (TCAs) (4%), benzodiazepines (4%), and zopiclone (4%). Seventy-one (69%) were evaluated as accidental deaths and 32 (31%) as suicides. In 70% of all cases, and in 34% of suicides, the deceased was classified as drug or alcohol dependent. When compared with the 2981 non-fatal acute poisonings registered during the study period, the case fatality rate was 3% (95% C.I., 0.03-0.04). Methanol, TCAs, and antihistamines had the highest case fatality rates; 33% (95% C.I., 0.008-0.91), 14% (95% C.I., 0.04-0.33), and 10% (95% C.I., 0.02-0.27), respectively.

Conclusions: Three per cent of all acute poisonings were fatal, and nine out of ten deaths by acute poisonings occurred outside hospital. Two-thirds were evaluated as accidental deaths. Although case fatality rates were highest for methanol, TCAs, and antihistamines, most deaths were caused by opiates or opioids.
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http://dx.doi.org/10.1186/1471-227X-10-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889934PMC
June 2010

Pre-hospital treatment of acute poisonings in Oslo.

BMC Emerg Med 2008 Nov 24;8:15. Epub 2008 Nov 24.

Department of Acute Medicine, Ullevaal University Hospital, Oslo, Norway.

Background: Poisoned patients are often treated in and discharged from pre-hospital health care settings. Studies of poisonings should therefore not only include hospitalized patients.

Aims: To describe the acutely poisoned patients treated by ambulance personnel and in an outpatient clinic; compare patients transferred to a higher treatment level with those discharged without transfer; and study the one-week mortality after pre-hospital discharge.

Methods: A one-year multi-centre study with prospective inclusion of all acutely poisoned patients > or = 16 years of age treated in ambulances, an outpatient clinic, and hospitals in Oslo.

Results: A total of 3757 health service contacts from 2997 poisoning episodes were recorded: 1860 were treated in ambulances, of which 15 died and 750 (40%) were discharged without transfer; 956 were treated in outpatient clinic, of which 801 (84%) were discharged without transfer; and 941 episodes were treated in hospitals. Patients discharged alive after ambulance treatment were mainly poisoned by opiates (70%), were frequently comatose (35%), had respiratory depression (37%), and many received naloxone (49%). The majority of the patients discharged from the outpatient clinic were poisoned by ethanol (55%), fewer were comatose (10%), and they rarely had respiratory depression (4%). Among the hospitalized, pharmaceutical poisonings were most common (58%), 23% were comatose, and 7% had respiratory depression. Male patients comprised 69% of the pre-hospital discharges, but only 46% of the hospitalized patients. Except for one patient, who died of a new heroin overdose two days following discharge from an ambulance, there were no deaths during the first week after the poisonings in the 90% of the pre-hospital discharged patients with known identity.

Conclusion: More than half of the poisoned patients treated in pre-hospital treatment settings were discharged without transfer to higher levels. These poisonings were more often caused by drug and alcohol abuse than in those who were hospitalized, and more than two-thirds were males. Almost half of those discharged from ambulances received an antidote. The pre-hospital treatment of these poisonings appears safe regarding short-term mortality.
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http://dx.doi.org/10.1186/1471-227X-8-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605443PMC
November 2008

Increased serum formate in the diagnosis of methanol poisoning.

J Anal Toxicol 2005 Sep;29(6):586-8

Department of Acute Medicine, Ullevaal University Hospital, NO-0407 Oslo, Norway.

Early diagnosis is essential for successful treatment in methanol poisoning. Methanol detection by gas chromatography is not available in most hospitals. Methanol increases the osmolal gap in serum and its metabolite formate increases the anion gap. The sensitivity of these indirect diagnostic methods is not good at low concentrations of methanol or formate. We therefore studied the usefulness of formate measurement in diagnosing methanol poisoning. In 15 patients poisoned with methanol, serum formate was measured enzymatically on a Cobas Mira analyzer using formate dehydrogenase and nicotinamid adenine dinucleotid. Day-to-day coefficient of variation was 5%, and the upper reference limit was 2 mg/dL (0.4 mmol/L). Methanol was detected in all 15 patients of whom 14 had elevated serum formate concentrations. Anion gap was increased in 11 of 11, and osmolal gap in 11 patients of 15 examined. Metabolic acidosis was present in 12 of 15 patients, but pH was below 7.30 in only 9 of them. Four patients with no symptoms had formate concentrations in the range 2-38 mg/dL (0.5-8.3 mmol/L), indicating that increased serum formate was a sensitive indicator of methanol poisoning. Our results proved formate analyzes to be a simple, sensitive, and specific way of diagnosing methanol poisoning. Confounders are patients admitted early, or concomitant ethanol ingestion, and therefore no acidosis. This problem may, however, be omitted by repeated formate analysis in patients developing metabolic acidosis.
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http://dx.doi.org/10.1093/jat/29.6.586DOI Listing
September 2005