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.

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.

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.

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.

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.

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.

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.

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.

Late-onset Ochrobactrum anthropi sepsis in a preterm neonate with congenital urinary tract abnormalities.

Recent trends in late-onset neonatal sepsis have revealed an increase in Gram-negative organisms as causative agents. Ochrobactrum anthropi is an emerging human pathogen that has been reported primarily in immunocompromised hosts, especially those with indwelling catheters or other medical devices. We report the occurrence of late-onset urosepsis secondary to O. anthropi in a preterm neonate with posterior urethral valves and review the salient features of the pathogen and its management.

Psychoactive substances in seriously injured drivers in Denmark.

This study assesses the presence of a number of psychoactive substances, including alcohol, based on blood samples from 840 seriously injured drivers admitted to five selected hospitals located in five different regions of Denmark. The study was a part of the EU 6th framework program DRUID (Driving Under the Influence of Drugs, Alcohol and Medicines). Blood samples were screened for 30 illegal and legal psychoactive substances and metabolites as well as ethanol. Danish legal limits were used to evaluate the frequency of drivers violating the Danish legislation while limit of quantification (LOQ) was used for monitoring positive drivers. Tramadol is not included in the Danish legislation therefore the general cut off, as decided in the DRUID project was used. Overall, ethanol (18%) was the most frequently identified compound (alone or in combination with other drugs) exceeding the legal limit, which is 0.53g/l in Denmark. The percentage of seriously injured drivers testing positive for medicinal drugs at levels above the Danish legal limit was 6.8%. Benzodiazepines and Z-drugs (6.4%) comprised the majority of this group. One or more illegal drugs (primarily amphetamines and cannabis) were found to be above the Danish legal limit in 4.9% of injured drivers. Young men (median age 31 years) were over-represented among injured drivers who violated Danish law for alcohol and drugs. Diazepam (4.4%), tramadol (3.2%), and clonazepam (3.0%) were the medicinal drugs most frequently detected at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and methamphetamine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%), including the metabolite benzoylecgonine, were the most frequently detected illegal drugs. A driver could be positive for more than one substance; therefore, percentages are not mutually exclusive. Poly-drug use was observed in 112 (13%) seriously injured drivers. Tramadol was detected above DRUID cutoffs in 2.1% of seriously injured drivers. This is 3.5 times that observed in a Danish survey of randomly selected drivers. Moreover, illegal and medicinal drug levels above the Danish legal limit were present more than 10 times as frequently as in injured drivers, whereas ethanol was present more than 30 times as frequently than in randomly selected drivers. The results indicate that there is an increased risk in traffic when driving under the influence of psychoactive drugs, especially alcohol in young male drivers.

Presence of psychoactive substances in oral fluid from randomly selected drivers in Denmark.

This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Oral fluid samples (n=3002) were collected randomly from drivers using a sampling scheme stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53g/l, which is the Danish legal limit. The percentage of drivers positive for medicinal drugs above the Danish legal concentration limit was 0.4%; while, 0.3% of the drivers tested positive for one or more illicit drug at concentrations exceeding the Danish legal limit. Tetrahydrocannabinol, cocaine, and amphetamine were the most frequent illicit drugs detected above the limit of quantitation (LOQ); while, codeine, tramadol, zopiclone, and benzodiazepines were the most frequent legal drugs. Middle aged men (median age 47.5 years) dominated the drunk driving group, while the drivers positive for illegal drugs consisted mainly of young men (median age 26 years). Middle aged women (median age 44.5 years) often tested positive for benzodiazepines at concentrations exceeding the legal limits. Interestingly, 0.6% of drivers tested positive for tramadol, at concentrations above the DRUID cut off; although, tramadol is not included in the Danish list of narcotic drugs. It can be concluded that driving under the influence of drugs is as serious a road safety problem as drunk driving.

Fatal poisoning in drug addicts in the Nordic countries in 2007.

The frequency of medico-legally examined fatal poisonings in 2007 among drug addicts was investigated in five Nordic countries; Denmark, Finland, Iceland, Norway, and Sweden. The number of deaths, age, sex, place of death, main intoxicant, and other drugs present in blood samples were recorded to obtain national and comparable Nordic data, as well as data to compare with earlier studies in 2002, 1997, and 1991. Norway had the highest incidence of drug addict deaths by poisoning followed by Denmark, with 8.24 and 6.92 per 100,000 inhabitants, respectively. The death rates in Finland (4.02), Iceland (4.56), and Sweden (3.53) were about half that of Norway and Denmark. Compared with earlier studies, the death rates were unchanged in Denmark and Norway, but increased in Finland, Iceland, and Sweden. In all countries, fewer deaths (29-35%) were recorded in the capital area compared with earlier studies. Females accounted for 11-19% of the fatal poisonings. Iceland deviates with a more equal distribution between men and women (40%). Deaths from methadone overdoses increased in all Nordic countries, and methadone was the main intoxicant in Denmark in 2007, accounting for 51% of the poisonings. In Norway and Sweden, heroin/morphine was still the main intoxicant with a frequency of 68% and 48%, respectively. In Iceland, 3 deaths each were due to heroin/morphine and methadone, respectively. Finland differs from other Nordic countries in having a high number of poisonings caused by buprenorphine and very few caused by heroin/morphine. The total number of buprenorphine deaths in Finland doubled from 16 in 2002 to 32 in 2007, where it constituted 25% of deaths. The general toxicological screening program showed widespread multi-drug use in all countries. The median number of drugs per case varied from 3 to 5. The most frequently detected substances were heroin/morphine, methadone, buprenorphine, tramadol, amphetamine, cocaine, tetrahydrocannabinol, benzodiazepines and ethanol.

Comparison of conventional Papanicolaou smear and SurePath liquid-based cytology in the Copenhagen population screening programme for cervical cancer.

OBJECTIVE: To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. METHODS: A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). RESULTS: After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. CONCLUSIONS: This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.

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.

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.

HFE mutations and hemochromatosis in Danish patients admitted for HFE genotyping.

Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate the efficiency with which different hospitals and general practitioners select patients for HH genotype and to determine the distribution of HFE mutations in such patients. Nine hundred unrelated patients from Danish hospitals and general practitioners (group A) and 69 consecutive patients from a specialized liver unit (group B) were examined for HFE substitutions using multiplex real-time polymerase chain reaction. In group A we found 13.0% (0%) C282Y homozygotes, 5.8% (2.6%) H63D/C282Y compound heterozygotes and 1.9% (3.1%) S65C heterozygotes. The values for 420 Danish blood donors are shown in parentheses. The distribution of genotypes in group B was similar to that of the blood donors. Serum ferritin, transferrin iron saturation and pathological data were collected from 38 randomly selected C282Y homozygotes, 36 H63D/C282Y compound heterozygotes, 19 H63D heterozygotes, 17 S65C heterozygotes and 144 wild-types. All of the C282Y homozygotes and 28% of the compound heterozygotes were diagnosed as HH patients. There was no evidence of HH in the H63D homozygotes or S65C heterozygotes. Moreover, 7 wild-type patients, 2 C282Y heterozygote patients and one H63D heterozygote patient fulfilled the criteria for HH. The significant enrichment of HH among associated genotype samples submitted for HFE testing indicates that the clinical selection is generally adequate. However, the study showed substantial deviation in the selection efficiency among the various hospitals and general practitioners.

Fatal poisoning in drug addicts in the Nordic countries.

The study includes medicolegally examined fatal poisonings among drug addicts in 1997 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden, and the results are compared to a similar investigation from 1991. A common definition of "drug addict" was applied by the participating countries. The highest death rate by poisoning in drug addicts was observed in Denmark, where it was 6.54 per 10(5)inhabitants, followed by Norway with 6.35, Sweden with 2.21, Finland with 1.63 and Iceland with 1.20 per 10(5)inhabitants. All countries showed a higher death rate in 1997 than in 1991. For all countries the distribution of deaths according to geographical regions showed a decreasing number of drug deaths in the metropolitan area and an increasing number in other cities. Heroin/morphine dominated as the cause of death and was responsible for about 90% of the cases in Norway. In Sweden and Denmark, however, heroin/morphine caused only about 70% of the fatal poisonings. About 30% of the fatal poisonings in Denmark and Sweden were caused by other group I drugs, in Denmark mainly methadone and in Sweden mainly propoxyphene. Apart from two cases in Sweden methadone deaths were not seen in the other Nordic countries. In Finland heroin/morphine deaths have increased from about 10% in 1991 to about 40% in 1997. Forty-four percent of the fatal poisonings in Finland were caused by other group I drugs, mainly codeine and propoxyphene. The two fatal poisonings in Iceland were caused by carbon monoxide. Only few deaths in this investigation were caused by amphetamine and cocaine. A widespread use of alcohol, cannabis and benzodiazepines, especially diazepam, was seen in all the countries.

[Designer drugs in Jutland]. / Designerdrugs i Jylland.

INTRODUCTION: The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. MATERIAL AND METHODS: All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. RESULTS: MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. DISCUSSION: MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

[Fatal intoxications among drug addicts in Denmark in 1997]. / Forgiftningsdødsfald blandt narkomaner i Danmark i 1997.

INTRODUCTION: The purpose of this study was to investigate fatal poisonings among drug addicts in 1997 and to compare the results to similar investigations from 1985 and 1991. MATERIAL AND METHODS: All fatal intoxications among drug addicts in Denmark in 1997, investigated at the three Institutes of Forensic Medicine in Denmark. RESULTS: The number of fatal intoxications increased by 32% from 1991 to 1997, mainly outside the metropolitan area, The average age increased from 32 to 36 years. The proportion of heroin/morphine intoxications increased from 57% to 71%. The most commonly used drugs were as in 1991 heroin/morphine, diazepam and methadone. The frequency of cocaine increased from one positive case in 1991 to 14% positive cases in 1997. DISCUSSION: This study showed an increasing number of fatal intoxications and changes in drug abuse pattern and place of death since 1991.

Circumventing multiple testing: a multilocus Monte Carlo approach to testing for association.

Advances in marker technology have made a dense marker map a reality. If each marker is considered separately, and separate tests for association with a disease gene are performed, then multiple testing becomes an issue. A common solution uses a Bonferroni correction to account for multiple tests performed. However, with dense marker maps, neighboring markers are tightly linked and may have associated alleles; thus tests at nearby marker loci may not be independent. When alleles at different marker loci are associated, the Bonferroni correction may lead to a conservative test, and hence a power loss. As an alternative, for tests of association that use family data, we propose a Monte Carlo procedure that provides a global assessment of significance. We examine the case of tightly linked markers with varying amounts of association between them. Using computer simulations, we study a family-based test for association (the transmission/disequilibrium test), and compare its power when either the Bonferroni or Monte Carlo procedure is used to determine significance. Our results show that when the alleles at different marker loci are not associated, using either procedure results in tests with similar power. However, when alleles at linked markers are associated, the test using the Monte Carlo procedure is more powerful than the test using the Bonferroni procedure. This proposed Monte Carlo procedure can be applied whenever it is suspected that markers examined have high amounts of association, or as a general approach to ensure appropriate significance levels and optimal power.