Health consequences of androgenic anabolic steroid use.

BACKGROUND: The lifetime prevalence of androgenic anabolic steroid abuse is estimated to be around 6% for men, but there is limited knowledge about the side effects of these drugs. OBJECTIVE: To investigate mortality and morbidity amongst users of androgenic anabolic steroids (AAS). METHODS: In this retrospective matched cohort study, 545 male subjects tested positive for AAS in Danish fitness centres during the period 3 January 2006 to 1 March 2018. Subjects were matched with 5450 male controls. In addition, 644 men who were sanctioned because they refused to submit to a doping test and 6440 controls were included as a replication cohort. RESULTS: Mortality was three times higher amongst users of AAS than amongst nonuser controls (hazard ratio 3.0, 95% CI 1.3-7.0). The median annual number of hospital contacts was 0.81 in the cohort of AAS users and 0.36 in the control cohort (P < 0.0001). Acne, gynaecomastia and erectile dysfunction affected more than 10% of the androgenic anabolic steroid users, and the prevalence of these disorders was significantly higher than in the control group (P < 0.0001). The results could be replicated in a similar cohort. CONCLUSION: Androgenic anabolic steroid users have an increased risk of dying and significantly more hospital admissions than their nonuser peers. Side effects of AAS and their metabolites were highly prevalent. Given the high rate of androgenic anabolic steroid abuse, these side effects are of public health concern.

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants.

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.

Paracetamol poisoning among immigrants in a department of hepatology.

INTRODUCTION: An increased incidence of suicides and suicidal behaviour among immigrants has been described in other countries. In Denmark, misuse of paracetamol is suspected in some foreign-born minority groups, although no data have been produced to substantiate this suspicion. METHODOLOGY: A retrospective study of the incidence of paracetamol poisoning in patients admitted to a specialised department of hepatology from 1994 to 1999 was carried out. RESULTS: Of a total of 580 patients, 56 (9.7%; 95%-confidence interval 7.2-12.1%) were immigrants, among whom a significant overrepresentation was found of immigrants from Turkey, Iran, Pakistan, and Lebanon (Observed/Expected-ratios of 1.95, 4.14, 2.67, and 2.45 respectively; p < 0.05). The immigrants differed from the Danish-born patients being younger (21 vs 35 years of age; p < 0.05), having a lower level of alcohol consumption (3% vs 30% with regular alcohol abuse; p < 0.05), and in general being less severely intoxicated (3% vs 22% developing hepatic encephalopathy; p < 0.05). Compared to the Danish-born patients, the immigrants more frequently stated socio-economic problems as the reason for their self-poisoning (29% vs 10%; p < 0.05). CONCLUSIONS: The study demonstrates an overrepresentation of immigrants among patients admitted with paracetamol poisoning in Denmark.

[Therapeutic monitoring by blood concentrations with the focus on cyclosporin A]. / Terapistyring efter blodkoncentrationer med fokus på ciclosporin A.

Cyclosporin A therapeutic drug monitoring with through concentrations results in a high frequency of toxicity or therapeutic failure. There is no simple relation between the through and the mean concentration, and thus the therapeutic effect. Estimation of the AUC on sparse sampling or population pharmacokinetic analysis and the Bayesian fit of the parameters are discussed.

[Paracetamol poisoning among immigrants in a department of hepatology]. / Indvandrere med paracetamolforgiftning på en hepatologisk afdeling.

INTRODUCTION: An increased incidence of suicides and suicidal behaviour among immigrants has been described in other countries. In Denmark, misuse of paracetamol is suspected in some foreign-born minority groups, although no data have been produced to substantiate this suspicion. MATERIALS AND METHODS: A retrospective study of the incidence of paracetamol poisoning in patients admitted to a specialised department of hepatology from 1994 to 1999 was carried out. RESULTS: Of a total of 580 patients, 56 (9.7%) were immigrants, among whom a significant overrepresentation was found of immigrants from Turkey, Iran, Pakistan, and Lebanon (observed/expected ratios of 1.95, 4.14, 2.67, and 2.45 respectively). The immigrants differed from the Danish-born patients in that they were younger (21 vs 35 years of age), had a lower level of alcohol consumption (3% vs 30% with regular alcohol abuse), and were in general less severely intoxicated (3% vs 22% developing hepatic encephalopathy). Compared to the Danish-born patients, the immigrants more frequently stated socio-economic problems as the reason for their self-poisoning (29% vs 10%). DISCUSSION: The study demonstrates an overrepresentation of immigrants among patients admitted with paracetamol poisoning in Denmark.

[Side-effects of N-acetylcysteine treatment in patients with paracetamol poisoning]. / Bivirkninger ved N-acetylcystein-behandling af paracetamolforgiftede patienter.

Treatment of paracetamol intoxication with N-acetylcysteine (NAC) is standard in Denmark. NAC is considered safe with relatively few side effects. It is recommended that all patients be treated irrespective of paracetamol dose or time from intoxication to treatment start. Consequently a higher number of patients will be treated with NAC than with previous regimens based on plasma concentrations of paracetamol. In this retrospective study we evaluated the incidence of side effects of NAC in 310 patients admitted to the Department of Hepatology, Rigshospitalet, Copenhagen, over a four-year period (1.1.1994-31.12.1997). Twenty-six (8.4%) patients developed side effects. Side effects were anaphylactoid, mainly from skin (25 rash, pruritus or flushing), in rare cases more serious (four bronchospasm, three angioedema, one hypotension). None were life-threatening and all patients received the full course of NAC. In all cases the recommended treatment with antihistamine or steroids against adverse effects was administered. We conclude that treatment with NAC is safe. Accordingly we find no reason to change the recommendation for treatment of paracetamol intoxication in Denmark.

[Recommendations for treatment of paracetamol poisoning. Danish Medical Society, Study of the Liver]. / Rekommandation for behandling af paracetamolforgiftning.

Based on recent reports concerning the efficacy of N-acetylcysteine (NAC) in paracetamol (acetaminophen) poisoning, guidelines for treatment and control of these patients are reviewed by a study group under the Danish Association for the Study of the Liver. It is recommended that NAC-treatment is initiated immediately after referral and continued for 36 hours in all cases. Further NAC-treatment should not be discontinued before a decrease in INR has been observed.

[Consumption of, overdose and fatal poisoning with analgesics in Denmark 1979-1986]. / Analgetikaforbrug, -overdosering og -dødsfald i Danmark 1979-1986.

During 1978-1987 the annual sale of analgetics increased by 28% to 164 millions defined daily doses (mDDD) per year. Paracetamol changed status to over-the-counter drug by 1.1.1984 as did combinations of acetylicsalicylic acid and codein 14.5.1984. The consumption of paracetamol increased rapidly to 47 mDDD/-year, the mortality steadily decreasing to 0.07 deaths/mDDD in 1986. The consumption of salicylics decreased from 113 to 94 mDDD, of which the salicylic/codein combination constituted an increasing fraction. The mortality of salicylics increased from 0.05 death/mDDD in 1983 to 0.27/mDDD in 1986. Opoids except dextropropoxyphene increased three times during the period, while the risk of fatal poisoning decreased from 10 to 5 deaths/mDDD. Dextropropoxyphene consumption was stable 1978-86 while mortality doubled from 59 to 121 per year. After a National Board of Health initiative, 66 dextropropoxyphene deaths were seen in 1987. Paracetamol mortality was 10 times lower than in England and Wales, where a dextropropoxyphene/paracetamole combination (not available in Denmark) was often involved. From a toxicological point of view over the counter status for combinations of strong and weak analgetics are not desirable.