Genomic landscape of treatment refractory metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. MATERIAL AND METHODS: Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. RESULTS: A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (n = 72) of the patients. A total of 31.3% (n = 25) of the patients received therapy either as targetable therapy outside an available trial (n = 2), FDA approved therapy (n = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (n = 21). CONCLUSION: Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.

Perspectives in allergen immunotherapy: 2017 and beyond.

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.

Novel approaches and perspectives in allergen immunotherapy.

In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients.

Claims for compensation after injuries related to airway management: a nationwide study covering 15 years.

BACKGROUND: Securing the airway is one of the most important responsibilities in anaesthesia. Injuries related to airway management can occur. Analysis from closed claims can help to identify patterns of injury, risk factors and areas for improvement. METHODS: All claims to The Norwegian System of Compensation to Patients from 1 January 2001 to 31 December 2015 within the medical specialty of anaesthesiology were studied. Data were extracted from this database for patients and coded by airway management procedures. RESULTS: Of 400 claims for injuries related to airway management, 359 were classified as 'non-severe' and 41 as 'severe'. Of the severe cases, 37% of injuries occurred during emergency procedures. Eighty-one claims resulted in compensation, and 319 were rejected. A total of €1,505,344 was paid to the claimants during the period. Claims of dental damage contributed to a numerically important, but financially modest, proportion of claims. More than half of the severe cases were caused by failed intubation or a misplaced endotracheal tube. CONCLUSION: Anaesthesia procedures are not without risk, and injuries can occur when securing the airway. The most common injury was dental trauma. Clear patterns of airway management that resulted in injuries are not apparent from our data, but 37% of severe cases were related to emergency procedures which suggest the need for additional vigilance. Guidelines for difficult intubation situations are well established, but adherence to such guidelines varies. Good planning of every general anaesthesia should involve consideration of possible airway problems and assessment of pre-existing poor dentition.

The incidence of psychoactive substances and alcohol among impaired drivers in Denmark in 2015-2019.

This study examines the presence of psychoactive drugs and alcohol in blood from apprehended drivers driving under the influence of drugs (DUID) and alcohol in Denmark in a five-year period from 2015 to 2019. Data were analysed with respect to gender, age, substances with concentrations above the Danish legal limit, arresting time of day and repeat arrest. By request of the police, the blood samples were subjected to analysis for alcohol and/or tetrahydrocannabinol (THC) alone, for "other drugs" (covering all drugs including new psychoactive substances (NPS), except THC, listed in the Danish list of narcotic drugs) or for both THC and other drugs. About the same number of alcohol traffic cases (37,960) and drug traffic cases (37,818) were submitted for analysis for the five-year period. The number of drug traffic cases per year increased from 5660 cases in 2015 to 9505 cases in 2019, while the number of alcohol traffic cases per year (average, 7600) was unchanged. Ethanol (89.2%) was the overall most frequent single substance, followed by THC (68.2%). CNS stimulants (46.8%) were the second most prevalent group of non-alcoholic drugs. Cocaine (23.8%) and amphetamine (22.9%) were the most frequent CNS stimulants. The proportion of CNS-stimulant positive drivers more than doubled in ten years. Benzodiazepines/z-hypnotics (12.7%) were the third most prevalent drug group detected, with clonazepam (8%) as the most frequent drug. Opioids were above the legal limit in 9.8% of the cases. NPS was above the legal limit in 128 cases (0.6%). Poly-drug use occurred in 40% of the DUID cases in the requested groups: other drug or other drug/THC. Young males dominated the DUID cases (median age 26). Drink-drivers (median age 39) were also mainly men, but the age distribution was equally spread over the age groups. Re-arrest occurred more often in DUID drivers (18-29%) than in drinking drivers (6-12%). DUID was evenly spread over the week, while drink-driving was most frequent on weekends. This study is an important supplement to the knowledge of drug use in Denmark. It was the well-known psychoactive substances that were detected. Only a few NPS occurred. However, the abuse pattern has changed, and CNS stimulants now account for a much higher proportion than earlier. Our results indicate a drug use problem among DUID drivers. This gives rise to concern because of a risk of traffic accidents. Treating the underlying abuse problem is therefore recommended, rather than focusing solely on prosecuting.

Fatal poisoning in drug addicts in the Nordic countries in 2017.

This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012. The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7-23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14-70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years. Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland. Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4-6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland.

Association studies of genetic scores of serum vitamin B12 and folate levels with symptoms of depression and anxiety in two danish population studies.

BACKGROUND/OBJECTIVES: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety. SUBJECTS/METHODS: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety. RESULTS: An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302-0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331-2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101-3.602)), anxiety (pooled OR 0.619 (95%CI 0.110-3.495)), combined score or history of doctor-diagnosed depression or anxiety. CONCLUSION: Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.

Adding confidence to gene expression clustering.

It has been well established that gene expression data contain large amounts of random variation that affects both the analysis and the results of microarray experiments. Typically, microarray data are either tested for differential expression between conditions or grouped on the basis of profiles that are assessed temporally or across genetic or environmental conditions. While testing differential expression relies on levels of certainty to evaluate the relative worth of various analyses, cluster analysis is exploratory in nature and has not had the benefit of any judgment of statistical inference. By using a novel dissimilarity function to ascertain gene expression clusters and conditional randomization of the data space to illuminate distinctions between statistically significant clusters of gene expression patterns, we aim to provide a level of confidence to inferred clusters of gene expression data. We apply both permutation and convex hull approaches for randomization of the data space and show that both methods can provide an effective assessment of gene expression profiles whose coregulation is statistically different from that expected by random chance alone.

Properties of statistical tests of neutrality for DNA polymorphism data.

A class of statistical tests based on molecular polymorphism data is studied to determine size and power properties. The class includes Tajima's D statistic as well as the D* and F* tests proposed by Fu and Li. A new method of constructing critical values for these tests is described. Simulations indicate that Tajima's test is generally most powerful against the alternative hypotheses of selective sweep, population bottleneck, and population subdivision, among tests within this class. However, even Tajima's test can detect a selective sweep or bottleneck only if it has occurred within a specific interval of time in the recent past or population subdivision only when it has persisted for a very long time. For greatest power against the particular alternatives studied here, it is better to sequence more alleles than more sites.

Fatal poisoning in drug addicts in the Nordic countries in 2012.

This report is a follow-up to a study on fatal poisoning in drug addicts conducted in 2012 by a Nordic working group. Here we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on sex, number of deaths, places of death, age, main intoxicants and other drugs detected in the blood were recorded. National data are presented and compared between the Nordic countries and with data from similar studies conducted in 1991, 1997, 2002 and 2007. The death rates (number of deaths per 100,000 inhabitants) increased in drug addicts in Finland, Iceland and Sweden but decreased in Norway compared to the rates in earlier studies. The death rate was stable in Denmark from 1991 to 2012. The death rate remained highest in Norway (5.79) followed by Denmark (5.19) and Iceland (5.16). The differences between the countries diminished compared to earlier studies, with death rates in Finland (4.61) and Sweden (4.17) approaching the levels in the other countries. Women accounted for 15-27% of the fatal poisonings. The median age of the deceased drug addicts was still highest in Denmark, and deaths of addicts >45 years old increased in all countries. Opioids remained the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin/morphine, medicinal opioids, cocaine, amphetamines, benzodiazepines and alcohol were the main abused drugs. However, less widely used drugs, like gamma-hydroxybutyric acid (GHB), methylphenidate, fentanyl and pregabalin, appeared in all countries. New psychotropic substances emerged in all countries, with the largest selection, including MDPV, alpha-PVP and 5-IT, seen in Finland and Sweden.

Dose-response relationship and incidence of adverse drug reactions with isradipine in patients with essential hypertension.

Based on pooled data from three randomized placebo-controlled dose-finding studies in a total of 489 patients, the dose-response relationship for efficacy and adverse events was estimated, using the Michaelis-Menten equation: Effect = maximal effect multiplied by dose/constant plus dose. Three conclusions were derived from the pooled data: (1) A marked increase in efficacy is seen when the reduction in diastolic blood pressure after one week of treatment is compared with that seen after five weeks of treatment, with both placebo and active treatment. Thus, dose increases should preferably be made at intervals of at least four weeks to avoid unnecessarily high doses. (2) Isradipine 2.5 mg twice daily offers an efficacy of approximately 80 percent of the maximum with an incidence of adverse events which, statistically, is not significantly different from the incidence seen in the placebo groups. (3) With continued treatment, a marked decrease in the incidence of adverse drug reactions is seen between the first and fifth weeks, especially with doses at 1.25 and 2.5 mg twice daily. However, with doses above 10 mg per day, this effect is no longer evident.

Role of hypercholesterolemia in accelerated transplant coronary vasculopathy: results of surgical therapy with partial ileal bypass in rabbits undergoing heterotopic heart transplantation.

BACKGROUND: We tested the hypothesis that plasma cholesterol lowering action of partial ileal bypass (PIB) is beneficial in mitigating accelerated transplantation coronary vasculopathy. METHODS: Forty-one New Zealand white rabbits were randomized to receive a normal (n = 21) or 1% cholesterol diet (n = 20). They underwent heterotopic heart transplantation with sham-PIB (n = 19) or PIB (n = 22) and immunosuppression with cyclosporine A (CyA). RESULTS: CyA increased plasma cholesterol of rabbits receiving a normal diet. This effect was mitigated by PIB (101 +/- 50 mg/dl CyA vs baseline 24 +/- 8, p < 0.001; vs 54 +/- 25 mg/dl with PIB, p < 0.05). In cholesterol-fed rabbits, PIB decreased plasma cholesterol levels (520 +/- 236 mg/dl PIB vs baseline 720 +/- 359, p < 0.05; vs 1502 +/- 253 mg/dl with sham PIB, p < 0.00001). Coronary arteries (CA) of 21 5-week survivors were evaluated by light microscopy and digital morphometry. No rejection was noted. Histologic study revealed vasculopathy in 3% of 705 native and 18% of 654 transplant CA (p < 0.05). Graft vasculopathy (GV) was present in 25% of 365 CA of sham-PIB and 10% of 289 CA of PIB rabbits (p = 0.07). In cholesterol-fed rabbits, GV was characterized by fatty proliferative lesions in 75% of 91 pathologic CA of sham and 21% of 28 pathologic CA of PIB rabbits (p < 0.05). Graft intimal hyperplasia was not correlated with cholesterol intake or PIB and was present in 18 of 119 pathologic CA. CONCLUSIONS: GV was characterized by fatty intimal proliferation, fibrous intimal hyperplasia, and a "mixed type." Fibrous intimal hyperplasia developed in native and transplanted hearts, and CyA seemed to promote this state. Hypercholesterolemia promoted fatty proliferative lesions, worsening GV. PIB significantly decreased total cholesterol and retarded fatty proliferation of CA of native and transplanted hearts but did not prevent intimal hyperplastic vasculopathy. Therapy of hypercholesterolemia is recommended to at least mitigate the fatty intimal proliferation of GV.

Recycling with nicotine patches in smoking cessation.

The aim was to evaluate if recycling of failures from a smoking cessation study may be of value. The study comprised 126 smokers (50%) of 252 failures, from a double-blind smoking cessation trial with nicotine patch, who accepted recycling after 1 year. Subjects were allocated nicotine patches delivering 15, 20 or 25 mg of nicotine (over 16 hours) according to their base-line saliva cotinine concentrations in an open trial. The treatment period was 12 weeks followed by tapering over 6 weeks. The percentage of quitters after 3, 12, 26, and 52 weeks was 44, 20, 7 and 6%, respectively. After 26 weeks, all subjects had relapsed in the group previously treated with active nicotine patch compared with 12% abstainers in the previous placebo subjects. The sustained abstinence rate without slips after one year was 2%. Recycling does not seem to be of long-term clinical relevance in our set-up for subjects initially treated with nicotine, but of some value in subjects quitting without nicotine therapy initially.

A randomized comparison of isradipine slow release given once daily with isradipine twice daily on 24 hour blood pressure in hypertensive patients.

Isradipine, a new calcium channel blocker, was given to 32 patients with mild to moderate essential hypertension. After a run-in period of three weeks, 32 patients were randomized double-blindly to six weeks' treatment with either isradipine 2.5 mg twice daily or isradipine 5.0 mg once daily in a modified release formulation. Based on conventional 'clinic' BP measurements 12 or 24 hours postdose, the two treatments resulted in clinically relevant BP reduction (16/11 and 19/15 mmHg) without reflex tachycardia. No differences were seen between the groups. Efficacy increased throughout the study period. By determination of the 24 hour BP profile with a noninvasive method, the two groups were comparable during the placebo period, and no differences were seen between the two treatments. Both treatments resulted in satisfactory BP reduction during 24 hours (daily reduction of 4/6 and 12/9 mmHg twice daily and once daily dosing respectively). One third of the patients had 'white-coat' hypertension based on ambulatory daytime mean BPs, compared with conventional measurements. No relationship was found between the initial BP lowering effect and the effect after long-term treatment with isradipine in either dose.

Renal myoglobin in drug addicts: occurrence and significance in a postmortem study.

In a 3-year period (1989-1991) a non-selected, consecutive series of 62 deaths in drug addicts was autopsied at the Forensic Institute in Odense. The kidney sections from these addicts were examined for the presence of renal myoglobin using immunohistochemical methods. A reference group consisting of a non-selected, non-consecutive series of 58 autopsied non-addicts was likewise investigated for the presence of renal myoglobin. No major differences were demonstrated between the two groups. The presence of renal myoglobin probably indicates a prolonged course of events prior to death (unconsciousness, immobilization, hypovolemia). In sufficient amounts, renal myoglobin may be of importance as a cause of death or a contributing factor to death in both drug addicts and non-addicts.

A prospective toxicology analysis in alcoholics.

A prospective and comprehensive investigation was done on 73 medico-legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis was found to be the cause of death in 7%. Altogether toxicology analyses were necessary for determining the cause of death in 51% of the cases. In four cases the cause of death would not have been found, had this investigation not been made. It is concluded that toxicology analyses should be the rule rather than the exception in deaths in alcoholics.

Narcotics at street level in Denmark. A prospective investigation from 1995 to 2000.

This article describes an investigation of illicit drugs at street level in six selected police districts in different regions of Denmark. The investigation was carried out during a 6-year period from 1995 to 2000. During the period, a total of 1244 samples were examined, as about 200 samples were seized each year. A total of 94% of the seized samples were familiar drugs: heroin base, heroin hydrochloride, cocaine hydrochloride and amphetamine sulphate. Only 2% of the samples contained designer drugs. From having constituted 53% of the samples in 1995, the frequency of heroin base fell during the period to 27% of the samples in 2000. The frequency of heroin hydrochloride was unchanged. In the same period, the frequency of cocaine hydrochloride increased from 10% of the samples in 1995 to about 25% of the samples in 2000. Apart from a few exceptions, cocaine had the same extension in all regions of Denmark after 1996. Amphetamine was more frequent in the west of Denmark, while heroin hydrochloride was more frequent in central Denmark. The purity of heroin base was lower in the period 1997-1999 than in the other years. During the entire period, the purity of cocaine hydrochloride and amphetamine sulphate fell, while the purity of heroin hydrochloride was unchanged. No significant differences between the various regions of Denmark were detected during the period in the purity of heroin hydrochloride, heroin base, cocaine hydrochloride or amphetamine sulphate. MDMA was the most frequent designer drug, but other types of designer drugs such as MDA and MDE and the less common PMA, PMMA and MBDB were also found.

Deaths among drug addicts in Denmark in 1987-1991.

In the period 1987-1991 a total of 739 fatalities among drug addicts was investigated at the three University Institutes of Forensic Medicine in Denmark. The annual number rose from 130-140 in the first 4 years to 192 in 1991, and 80% were males. The mean and median age for both males and females increased by 1 year in the period. The main drug of abuse was heroin, in most cases supplemented by various other drugs, and in almost all cases taken intravenously. In about one-third of the cases each year there was information of abuse of alcohol in addition. In the poisoning cases, the main drug of poisoning was morphine/heroin, constituting 35-55% of the cases each year. As regards methadone-poisoning cases, the number increased significantly in 1991 compared to the first 4 years. Furthermore, the number and proportion of addicts dying while in methadone treatment increased during the 5-year period. In about half of the methadone poisoning cases, there was information of methadone treatment at the time of death. The other half obviously obtained the methadone completely illegally. Ketobemidone was the third most frequent drug of poisoning, while propoxyphene and barbituric acid only were found in a very few cases each. The results are compared to those from an earlier investigation concerning drug deaths in Denmark in 1968-1986. The importance of registering drug deaths is emphasized.

Drug addict deaths in the Nordic countries: a study based on medicolegally examined cases in the five Nordic countries in 1991.

The study includes medicolegally examined deaths among drug addicts in 1991 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition of 'drug addict' was applied by the participating countries. The greatest number of drug addict deaths per 10(5) inhabitants was observed in Denmark followed, in descending order by Norway, Sweden, Finland and finally Iceland with only four deaths. The main difference between the countries was found in the number of fatal poisonings. The distribution according to geographical regions showed that about half of all drug addict deaths occurred in the metropolitan areas. Of the capitals, the greatest number of fatal poisonings per 10(5) inhabitants was seen in Oslo, followed by Copenhagen with a similar number, Stockholm with only the half, and Helsinki with a quarter. Heroin/morphine dominated as cause of death in fatal poisonings in Norway and Sweden. In Denmark, heroin/morphine caused about half of the fatal poisonings only, and nearly one third of the fatal poisonings was caused by methadone. Except for two cases in Sweden, methadone deaths were not seen in the other Nordic countries. Amphetamine caused one tenth of the fatal poisonings in Sweden. In Finland only one tenth of the deaths were caused by heroin/morphine and more by codeine, ethylmorphine and different drugs and poisons not classified in Single Convention on Narcotic Drugs 1961 or the International Convention on Psychotropic Substances 1971. A widespread use of alcohol, cannabis and benzodiazepines, diazepam especially, was seen in all the countries.

Fatal poisonings in young drug addicts in the Nordic countries: a comparison between 1984-1985 and 1991.

Fatal poisonings among young drug addicts (15-34 years) in the five Nordic countries, Denmark, Finland, Iceland, Norway and Sweden in 1991 were investigated and compared to a similar investigation for 1984-1985 (Sweden for 1984 only). A common definition of 'drug addict' has been applied by the participating countries. In both investigations, the greatest number of drug addict deaths was seen in Denmark calculated per 10(5) inhabitants, followed in descending order by Norway, Sweden, Finland and Iceland. An increased number of deaths was observed from 1984-1985 to 1991 in all five countries. The increase in Denmark and Sweden was small while the number of deaths was more than doubled in Norway and Finland. The increased number of cases in Norway and Sweden in 1991 is mainly due to a greater number of deaths in the age group 25-34 years. In Finland, the increased number was seen mainly in the age group 15-24 years. In the two investigations heroin/morphine caused most of the fatal poisonings in Norway and Sweden. In Denmark, heroin/morphine caused about half of the fatal poisonings only, and strong analgesics other than heroin/morphine caused about one third of the deaths. In 1984-1985 it was methadone, propoxyphene and ketobemidone and in 1991 mostly methadone. The number of heroin/morphine related deaths in Finland increased from 1984-1985 to 1991, but other drugs and poisons caused a much higher proportion of the deaths. Pentobarbital caused the only fatal poisoning in Iceland in 1991.