Ulf Bergman

Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

Objective To assess the risk of attempted suicide before, during, and after treatment with isotretinoin for severe acne. Design Retrospective cohort study linking a named patient register of isotretinoin users (1980-9) to hospital discharge and cause of death registers (1980-2001). Setting Sweden, 1980-2001. Population 5756 patients aged 15 to 49 years prescribed isotretinoin for severe acne observed for 17 197 person years before, 2905 person years during, and 87 120 person years after treatment. Main outcome measures Standardised incidence ratio (observed number divided by expected number of suicide attempts standardised by sex, age, and calendar year), calculated up to three years before, during, and up to 15 years after end of treatment. Results 128 patients were admitted to hospital for attempted suicide. During the year before treatment, the standardised incidence ratio for attempted suicide was raised: 1.57 (95% confidence interval 0.86 to 2.63) for all (including repeat) attempts and 1.36 (0.65 to 2.50) counting only first attempts. The standardised incidence ratio during and up to six months after treatment was 1.78 (1.04 to 2.85) for all attempts and 1.93 (1.08 to 3.18) for first attempts. Three years after treatment stopped, the observed number of attempts was close to the expected number and remained so during the 15 years of follow-up: standardised incidence ratio 1.04 (0.74 to 1.43) for all attempts and 0.97 (0.64 to 1.40) for first attempts. Twelve (38%) of 32 patients who made their first suicide attempt before treatment made a new attempt or committed suicide thereafter. In contrast, 10 (71%) of the 14 who made their first suicide attempt within six months after treatment stopped made a new attempt or committed suicide during follow-up (two sample test of proportions, P=0.034). The number needed to harm was 2300 new six month treatments per year for one additional first suicide attempt to occur and 5000 per year for one additional repeat attempt. Conclusions An increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin, which motivates a close monitoring of patients for suicidal behaviour for up to a year after treatment has ended. However, the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established. As patients with a history of suicide attempts before treatment made new attempts to a lesser extent than did patients who started such behaviour in connection with treatment, patients with severe acne should not automatically have isotretinoin treatment withheld because of a history of attempted suicide.

Erratum to: Adverse Drug Reactions and Impaired Renal Function in Elderly Patients Admitted to the Emergency Department

Background Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk.

Differences in drug utilisation between men and women: a cross-sectional analysis of all dispensed drugs in Sweden

Objectives Ascertain the extent of differences between men and women in dispensed drugs since there is a lack of comprehensive overviews on sex differences in the use of prescription drugs. Design Cross-sectional population database analysis. Methods Data on all dispensed drugs in 2010 to the entire Swedish population (9.3 million inhabitants) were obtained from the Swedish Prescribed Drug Register. All pharmacological groups with ambulatory care prescribing accounting for >75% of the total volume in Defined Daily Doses and a prevalence of >1% were included in the analysis. Crude and age-adjusted differences in prevalence and incidence were calculated as risk ratios (RRs) of women/men. Results In all, 2.8 million men (59%) and 3.6 million women (76%) were dispensed at least one prescribed drug during 2010. Women were dispensed more drugs in all age groups except among children under the age of 10. The largest sex difference in prevalence in absolute numbers was found for antibiotics that were more common in women, 265.5 patients (PAT)/1000 women and 191.3 PAT/1000 men, respectively. This was followed by thyroid therapy (65.7 PAT/1000 women and 13.1 PAT/1000 men) and antidepressants (106.6 PAT/1000 women and 55.4 PAT/1000 men). Age-adjusted relative sex differences in prevalence were found in 48 of the 50 identified pharmacological groups. The pharmacological groups with the largest relative differences of dispensed drugs were systemic antimycotics (RR 6.6 CI 6.4 to 6.7), drugs for osteoporosis (RR 4.9 CI 4.9 to 5.0) and thyroid therapy (RR 4.5 CI 4.4 to 4.5), which were dispensed to women to a higher degree. Antigout agents (RR 0.4 CI 0.4 to 0.4), psychostimulants (RR 0.6 CI 0.6 to 0.6) and ACE inhibitors (RR 0.7 CI 0.7 to 0.7) were dispensed to men to a larger proportion. Conclusions Substantial differences in the prevalence and incidence of dispensed drugs were found between men and women. Some differences may be rational and desirable and related to differences between the sexes in the incidence or prevalence of disease or by biological differences. Other differences are more difficult to explain on medical grounds and may indicate unequal treatment.

Pulmonary embolism associated with the use of anabolic steroids

We present the case of a 56-year-old man with deep vein thrombosis (DVT) and pulmonary embolism (PE). He had been given intramuscular injections of testosterone and the anabolic-androgenic steroid nandrolone, due to a muscle injury, a total of three times prior to manifestation of the symptoms. An ultrasonographic examination of the right leg revealed a DVT and computed tomography of the pulmonary arteries showed PE. The thromboembolic episodes in this previously healthy patient were in all probability associated with intramuscular injections of testosterone and nandrolone, to which there is a clear correlation in time.

Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study.

To undertake a multi‐country study to investigate the risk of acute hyperglycaemia with antipsychotic use.

Outpatient antibiotic use and assessment of antibiotic guidelines in Chinese children’s hospitals

PurposeOur aim was to investigate outpatient antibiotic use and assess the impacts of intervention in five Chinese children’s hospitals from 2002 to 2006.MethodsThe Anatomical Therapeutical Chemical Classification/Defined Daily Doses and Drug Utilization 90% methodologies were used. We also analyzed the relationship between antibiotic consumption and resistant rate in one of the hospitals.ResultsThe overall antibiotic consumption decreased during the intervention period in some hospitals, and the variation in use between hospitals was also reduced. A decrease in penicillins and first-generation cephalosporins, and an increase in third-generation cephalosporins as well as in the combinations of penicillins and β-lactamase inhibitors were observed. In addition, an increasing resistance to antibiotics was a concern due to antibiotic overconsumption.ConclusionsThe intervention had effects on the overall antibiotic use in outpatients. However, over the span of 5 years, there was a decrease in the use of narrow-spectrum antibiotics and an increase in broad-spectrum antibiotics.

Drug utilisation 90% (DU90%) profiles of antibiotics in five Chinese children's hospitals (2002-2006).

This study surveyed the pattern of inpatient antibiotic use in five Chinese childrens hospitals between 2002 and 2006, focusing on the antibiotics accounting for 90% of the volume utilised as well as the level of adherence to guidelines. The Anatomical Therapeutical Chemical Classification/Defined Daily Doses (ATC/DDD) and the drug utilisation 90% (DU90%) methodologies were used. In October 2004, national antibiotic guidelines were issued that divided antibiotics into non-restricted, restricted and special use grades. In five childrens hospitals, a total of 56 different systemic antibiotics were used during the study period. Antibiotics that could be injected accounted for 59.0-99.8%. beta-Lactam antibacterials (ATC codes J01C and J01D) were the most used subgroups. The numbers of antimicrobial agents and non-restricted antibiotics within the DU90% segment were 11-20 and 5-9, respectively. The proportion of non-restricted antibiotic consumption was ca. 40% in 2006 in four hospitals, which varied among hospitals during the period 2002-2005. There was considerable variation both in the pattern and amount of antibiotics used in the five hospitals, with amoxicillin/clavulanic acid, cefuroxime and cefazolin being the most commonly used substances. We also observed a decrease in the ranks of some restricted and special use antibiotics after the guidelines were issued in one hospital. The DU90% profiles were proven to be useful in studying the pattern of antibiotic use in hospitals. Finally, the study observed the effectiveness of guidelines for antibiotic use in some hospitals, although injectable antibiotics were widely used in childrens hospitals in China.

Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9

PurposeThe cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported.MethodsWe present a patient with Behçet’s disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed.ResultsThe patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls.ConclusionsOur finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.

Quality use of medicines: a new method of combining antibiotic consumption and sensitivity data—application in a Russian hospital†

Antibiotic use and resistance is subject of great concern. There is a need for internationally comparable and locally useful data collection and reporting. We developed a new method to combine and present data on antibiotic use and resistance in a figure in a Russian 1300 bed‐hospital.

Impact of restricted amoxicillin/clavulanic acid use on Escherichia coli resistance--antibiotic DU90% profiles with bacterial resistance rates: a visual presentation.

High use of amoxicillin/clavulanic acid (AMC) at the University Hospital Osijek (Croatia) contributed to high rates of resistance in Enterobacteriaceae, in particular Escherichia coli (50%). Thus, in order to decrease bacterial resistance, AMC use was restricted. We present results of the restriction on resistance amongst antibiotics accounting for 90% of antibiotic use [drug utilisation 90% (DU90%)]. Data were analysed on antibiotic use and microbiological susceptibility of E. coli during two 9-month periods, before and after the restriction of AMC use. Drug use was presented as numbers of defined daily doses (DDDs) and DDDs/100 bed-days. Resistance of E. coli to antibiotics was presented as percentages of isolated strains in the DU90% segment. Use of AMC was 16 DDDs/100 bed-days or 30% of all antibiotics before the intervention. Use of AMC fell to 2 DDDs/100 bed-days or 4% after the intervention, and resistance of E. coli fell from 37% to 11%. In conclusion, restricted use of AMC resulted in a significant decrease of E. coli resistance. DU90% resistance profiles are simple and useful tools in highlighting problems in antibiotic use and resistance but may also be useful in long-term follow-up of antibiotic policy.