Örjan Ericsson

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. Design Population based cohort study using data from the national health registers. Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. Participants More than 1.6 million infants born after gestational week 33. Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). Conclusions The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Enantioselective analysis of chloroquine and desethylchloroquine after oral administration of racemic chloroquine.

Summary: An enantioselective high-performance liquid chromatographic method for chloroquine and desethylchloroquine was developed using a chiral α1-acid glycoprotein column. This method was used to determine concentrations of chloroquine and desethylchloroquine enantiomers in plasma and urine from volunteers given single oral doses of racemic chloroquine. The disposition of the enantiomers was different. The renal clearance of the chloroquine enantiomers was indicative of stereoselective renal secretion of the drug, and evidence for stereoselective metabolism also was found.

Determination of chloroquine and its desethyl metabolite in whole blood: an application for samples collected in capillary tubes and dried on filter paper

A high performance liquid chromatography method for analysis of chloroquine and desethylchloroquine was adapted for 75 microliters aliquots of whole blood obtained by finger-prick and dried on filter paper. The precision of the method was satisfactory at whole blood concentrations of 40 nmol/L (coefficient of variation, 5%). The dried samples were stable for at least 7 weeks at 20 degrees C. The concentrations in venous whole blood and in dried samples correlated well. The correlation coefficient was 0.99 for chloroquine and 0.97 for desethylchloroquine. Chloroquine concentrations were marginally but significantly higher in venous whole blood. When fitted to a linear equation (y = bx + a) the relationship was y = 0.96x + 0.03. Desethylchloroquine concentrations did not differ significantly in venous whole blood and in finger-prick blood dried on filter paper. The method is specific and sensitive enough for pharmacokinetic studies and can be used in areas with limited technical facilities.

Education and drug use in Sweden--a nationwide register-based study.

To analyse educational variations in prescriptions dispensed in Sweden. A better knowledge of the use of drugs in the population, including socioeconomic distribution, is a prerequisite in efforts to estimate whether drugs are being prescribed and used according to need. This knowledge may also facilitate the identification of selection or confounding factors when analysing outcome or adverse side effects of drug treatment.

Equal access to treatment? Population-based follow-up of drugs dispensed to patients after acute myocardial infarction in Sweden

Background and ObjectiveThe establishment of national guidelines is one approach to creating equity in terms of access to care, and both internationally and in Sweden, guidelines have been developed for coronary heart disease. We have analysed drug treatment in Sweden according to national guidelines after acute myocardial infarction (AMI). The aim was to investigate whether there are differences between population groups according to sex, education, country of birth and diabetes.MethodsInformation was obtained from the Swedish Prescribed Drug Register on drugs dispensed between July and October 2005 for incident cases of AMI during the period 2003–2004 (n = 28,168). Data on socio-economic and demographic conditions were included. Dispensed drugs after AMI were compared to the recommended drug treatment according to Swedish and European guidelines – acetylsalicylic acid (ASA), β-blockers, lipid-lowering drugs and angiotensin-converting enzyme inhibitors (ACE inhibitors).ResultsWe found that, in general, there were only small differences between the sexes and between educational groups. The greatest differences were found in comparisons between regions of birth. In particular, foreign-born patients resident in Sweden but originally from outside the EU25 countries used fewer drugs than Swedish-born patients. The OR (odds ratio) for ASA was 0.73 [95% confidence interval (CI) 0.63–0.85], for β-blockers, 0.72 (0.63–0.83), for lipid-lowering drugs, 0.75 (0.65–0.86) and for ACE inhibitors, 0.76 (0.67–0.86).ConclusionsIn general, we found only slight differences – or none at all – between population groups in terms of drug treatment after AMI. Only among immigrants from outside the EU25 countries was there a tendency towards a lesser use of the recommended drugs according to the national guidelines.

Reversed-phase high-performance liquid chromatography determination of quinine in plasma, whole blood, urine, and samples dried on filter paper

The analysis of quinine in whole blood, plasma, urine, and samples dried on filter paper is described. Extraction was made with toluene followed by back-extraction into phosphate buffer. A reversed-phase liquid chromatography system with fluorescence detection was used. The within-day coefficient of variation of the method was 4–10% at the lower limit of determination (2 nM in plasma and 50 nM in whole blood, dried samples, and urine) and 2–4% at 10μM. The quinine concentration was found to be lower in whole blood than in plasma (mean ratio, plasma-whole blood, 1.17). The concentration in capillary blood was lower than that in venous blood (mean ratio, capillary blood-venous blood, 0.93).

Whole blood concentrations of chloroquine and desethylchloroquine during and after treatment of adult patients infected with Plasmodium vivax, P. ovale or P. malariae

Whole blood concentrations of chloroquine and desethychloroquine were determined during and after chloroquine treatment of 15 adult patients infected with P. vivax, P. ovale or P. malariae. The median of chloroquine concentrations remained practically unchanged in samples drawn three hours after initiation of treatment and in samples drawn immediately before the next dose of chloroquine. Concentrations of chloroquine remained above 1.0 mumol/litre for at least four days. The calculated sum of chloroquine and desethylchloroquine concentrations was above 1.0 mumol/litre for at least seven days. These concentrations are regarded as sufficient for treatment of P. vivax, P. ovale and P. malariae infections.

Prescription drugs Health in Sweden: The National Public Health Report 2012. Chapter 18

One of the most common medical actions performed by a doctor is to prescribe medicine for a patient [1]. In 2007, two in every three Swedes purchased at least one prescription drug at a pharmacy. The volume of drugs dispensed by pharmacies increases by 3–4 per cent every year. Recent years have seen the addition of a number of new and more effective drugs. The cost of prescription drugs rose by about 10 per cent annually in the period 1986–2002. However, the rate of increase has since slowed due to changes in the rules on pharmaceutical benefits, primarily those governing generic substitution. The combined cost of all medicines, i.e. prescription drugs, prescription-free drugs and drugs administered during hospital care, accounted for 11.6 per cent of total health and medical care costs in 2006. Pharmaceutical drug use patterns among women and men differ, as does drug use within social groups. Although these disparities are partly accounted for by variation in the disease burden across population groups, there are also gender and social disparities that cannot readily be attributed to differences in the needs of those who use prescription drugs. Examples include drugs for treating dementia and post-heart attack patients, which long-term follow-ups show are used more extensively by the highly educated than by the less well educated. People born outside the EU are less likely to use recommended medicines for heart attacks, heart failure, stroke and chronic obstructive pulmonary disease (COPD). The elderly are using prescription drugs to an increasing extent, a pattern that entails risks as well as benefits. A major proportion of the most frequently used drugs have a proven effect in treating many of the diseases and conditions common among the elderly. At the same time, use of multiple drugs, or polypharmacy, carries the risk of side effects and drug-drug interactions as different medications affect one another. The elderly are particularly vulnerable. Sensitive to drugs owing to dementia or multiple morbidity, they are among those most often exposed to polypharmacy. As a result, drug treatment is not always entirely appropriate. The Swedish National Board of Health and Welfare has accordingly developed quality indicators [2] and assessed and discussed the quality of drug treatments for the elderly in a number of reports [3–5]. According to the World Health Organization (WHO), deficiencies in drug prescribing are a principal cause of inadequate clinical treatment [6].

Determination of melarsoprol in biological fluids by high-performance liquid chromatography and characterisation of two stereoisomers by nuclear magnetic resonance spectroscopy

The analysis of melarsoprol in whole blood, plasma, urine and cerebrospinal fluid is described. Extraction was made with a mixture of chloroform and acetonitrile followed by back-extraction into phosphoric acid. A reversed-phase liquid chromatography system with ultraviolet detection was used. The relative standard deviation was 1% at concentrations around 10 mumol/l and 3-6% at the lower limit of determination (9 nmol/l in plasma, 93 nmol/l in whole blood, 45 nmol/l in urine and 10 nmol/l in cerebrospinal fluid). Melarsoprol is not a stable compound and samples to be stored for longer periods of time should be kept at -70 degrees C. Plasma samples can be stored at -20 degrees C for up to 2 months. Chromatography showed that melarsoprol contains two components. Using nuclear magnetic resonance spectroscopy the two components were shown to be diastereomers which slowly equilibrate by inversion of the configuration at the As atom.

Determination of pentamidine in whole blood, plasma, and urine by high-performance liquid chromatography.

The analysis of pentamidine in whole blood, plasma, and urine by liquid chromatography is described. Extraction was made with a mixture of acetonitrile and chloroform followed by back-extraction into phosphate buffer. A reversed-phase chromatographic system with fluorescence detection was used. The precision of the method was 5–7% at the lower limit of determination (16 nmol/L in plasma and hemolyzed whole blood, 27.7 nmol/L in urine).