Factors associated with switching and combination use of antidepressants in young Swedish adults.

AIMS: Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20-34 years. METHODS: Individuals, aged 20-34 years, who purchased an antidepressant in January-June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. RESULTS: A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93-2.57), and lower in individuals with high education: 0.64 (0.54-0.75), and shorter length of follow-up: 0.73 (0.62-0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05-2.49), and lower among individuals with short university education: 0.58 (0.43-0.78), those starting on mirtazapine: 0.78 (0.62-0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63-0.88). CONCLUSIONS: One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase patterns were associated with socioeconomic characteristics, in particular level of education, type of first purchased antidepressant, and level of care initiating treatment.

The use of complementary and alternative medicine in outpatients with inflammatory rheumatic diseases in Sweden.

OBJECTIVES: To study the use of complementary and alternative medicine (CAM) drugs and methods in patients with inflammatory rheumatic diseases, at rheumatology clinics in western Sweden, and to investigate possible associations between CAM-using habits and other characteristics of the patients. METHODS: Randomly selected rheumatology outpatients were asked to complete questionnaires about CAM usage, diagnoses, medication, quality of life (using the 36-item Short Form Health Survey, SF-36), fatigue (using the 20-item Multiple Fatigue Inventory, MFI-20), the Health Assessment Questionnaire (HAQ), and visual analogue scales (VAS) for global health, pain, and fatigue. RESULT: A total of 200 patients were included, 137 women and 63 men, mean age 55+/-16 and 54+/-15 years, respectively. Ongoing CAM use was reported by 58 patients (29%): 45 (22.5%) were taking CAM drugs, 20 (10%) were using CAM methods. Altogether 130 patients (65%) had used CAM at some time of their lives; 103 patients (51%) had used CAM drugs ever and 90 patients (45%) had used CAM methods ever. Women used more CAM drugs compared with men. Younger patients used more CAM. CAM use was associated with parameters indicating poorer health, mental component score (MCS) and physical component score (PCS) of SF-36, and VAS for global health and fatigue. Ongoing CAM method was associated with less use of immunomodulatory drugs. CONCLUSION: CAM use is widespread among rheumatology patients in Sweden. A total of 65% of the patients had experience of CAM treatment. Female sex, younger age, and poor health were associated with CAM utilization.

Haplotype association analysis of the polymorphisms Arg16Gly and Gln27Glu of the adrenergic beta2 receptor in a Swedish hypertensive population.

The Arg16Gly and the Gln27Glu polymorphisms in the gene for the beta2-adrenergic receptor (beta2AR) have been linked to an increased risk for cardiovascular disease. The aim of the present study was to evaluate the significance of these haplotypes for development of myocardial infarction (MI) as well as other cardiovascular phenotypes. In a prospective study cohort (CAPPP), 522 hypertensive patients (174 MI and 348 matched controls) were analysed for the Arg16Gly and the Gln27Glu polymorphisms by dynamic allele-specific hybridisation. The haplotype could successfully be determined in 516 patients. Haplotype was not significantly associated with MI. Systolic blood pressure (SBP) was higher in patients with Arg16Gly+Gln27Gln and lower in patients with Arg16Gly+Gln27Glu as compared with the other haplotypes. Haplotype was not associated with body mass index, diastolic blood pressure, cholesterol, LDL, HDL triglycerides or a diagnosis of diabetes mellitus. The present study found no evidence that haplotype for the two most common polymorphisms in the beta2AR are associated with development of MI in a Swedish hypertensive population, but haplotype may be associated with SBP.

Usefulness of serial electrocardiograms for diagnosis of acute myocardial infarction.

The purpose of this study was to determine whether the automated detection of acute myocardial infarction (AMI) by utilizing artificial neural networks was improved by using a previous electrocardiogram (ECG) in addition to the current ECG. A total of 4,691 ECGs were recorded from patients admitted to an emergency department due to suspected AMI. Of these, 902 ECGs, in which diagnoses of AMI were later confirmed, formed the study group, whereas the remaining 3,789 ECGS comprised the control group. For each ECG recorded, a previous ECG of the same patient was selected from the clinical electrocardiographic database. Artificial neural networks were then programmed to detect AMI based on either the current ECG only or on the combination of the previous and the current ECGs. On this basis, 3 assessors--a neural network, an experienced cardiologist, and an intern--separately classified the ECGs of the test group, with and without access to the previous ECG. The detection performance, as measured by the area under the receiver operating characteristic curve, showed an increase for all assessors with access to previous ECGs. The neural network improved from 0.85 to 0.88 (p = 0.02), the cardiologist from 0.79 to 0.81 (p = 0.36), and the intern from 0.71 to 0.78 (p <0.001). Thus, the performance of a neural network, detecting AMI in an ECG, is improved when a previous ECG is used as an additional input.

Differential effect of propofol on sympathetic neurotransmission in isolated human omental arteries and veins.

1. The present study was undertaken to elucidate the effect of propofol on sympathetic neurotransmission in isolated human omental vessels. 2. Segments of both arteries and veins were exposed to 0, 10(-7), 10(-6), 10(-5) or 10(-4)M propofol, and studied in vitro to determine effects on: (i) isometric tension after electrical field stimulation (EFS) or after exogenous administration of noradrenaline (NA); (ii) EFS-stimulated release of [3H]-NA from vessel segments preincubated with [3H]-NA; (iii) uptake of [3H]-NA. 3. Propofol at 10(-6) M enhanced EFS-induced contraction in artery segments, 10(-7) and 10(-5) M had no effect, and 10(-4) M propofol depressed EFS-induced contraction in both artery and vein segments. 4. Propofol did not affect the response to exogenous NA in artery and vein segments. 5. EFS-stimulated release of [3H]-NA was depressed by 10(-5) and 10(-4) M propofol in artery segments, and by 10(-4) M in vein segments. 6. Uptake of [3H]-NA was depressed by 10(-6)-10(-4) M propofol in artery but not in vein segments. 7. The results suggest that sympathetic neurotransmission is enhanced at clinical concentrations (10(-6) M) of propofol in human omental arteries, but not veins. This may be due to an increased availability of NA in the neuromuscular junction resulting from a reduced presynaptic reuptake. Propofol at probably supraclinical concentrations (10(-5)-10(-4) M) impairs the sympathetic neurotransmission in both human omental arteries and veins, probably due to an inhibitory effect on the NA release from the sympathetic nerves.

Endothelium-dependent relaxation by substance P in human isolated omental arteries and veins: relative contribution of prostanoids, nitric oxide and hyperpolarization.

1. The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile effect of the thromboxane A2 analogue U46619, (ii) endothelium-dependency and mediators of the relaxing effect of substance P (SP) and acetylcholine (ACh). 2. Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP-induced relaxation was measured in the presence of indomethacin (cyclo-oxygenase inhibitor), NG-monomethyl-L-arginine (L-NMMA, nitric oxide-synthase inhibitor), KCl (inhibitor of endothelium-dependent hyperpolarization), tetraethylammonium (TEA; non-selective inhibitor of K(+)-channels, with some preference for the high conductance Ca(2+)-activated K(+)-channel, BKCa), glibenclamide (inhibitor of the ATP-sensitive K(+)-channel) and/or clotrimazole (inhibitor of the cytochrome P450-system and the intermediate conductance Ca(2+)-activated K(+)-channel, IKCa). 3. U46619 contracted both the artery and the vein segments. Endothelium removal did not alter the contraction. 4. ACh caused neither contraction nor relaxation in artery and vein segments precontracted with U46619. 5. In both artery and vein segments precontracted with U46619, SP produced endothelium-dependent relaxation. The relaxation was unaffected by indomethacin, but was incompletely reduced by L-NMMA and KCl respectively. The L-NMMA-resistent relaxation was abolished in the presence of KCl. 6. TEA inhibited the SP-induced relaxation in artery and vein segments both in the presence and absence of L-NMMA and indomethacin, while glibenclamide and clotrimazole had no effect. 7. In conclusion, the SP-induced relaxation in human omental arteries and veins seems to be mediated via NO and endothelium-dependent hyperpolarization. KATP and IKCa are probably not involved in the hyperpolarization, but activation of BKCa may contribute to the hyperpolarization. Prostanoid synthesis and the cytochrome P450-system are probably not involved in the SP-induced relaxation in this area.

Severe hepatotoxic adverse reaction in a healthy schoolgirl after treatment with flucloxacillin.

This is the first detailed description of a severe hepatotoxic reaction in a previously healthy 9-year-old schoolgirl after ingestion of some flucloxacillin tablets. She was clinically well within one week and alanine aminotransferase in serum was normalized in one month. Follow up for more than one year was normal.

Effect of propofol on isolated human omental arteries and veins.

To elucidate the effect and mode of action of propofol on human vascular smooth muscle tension, we have investigated the effect of propofol alone and the effect of propofol on contractions induced by U46619, KCl and caffeine on isolated human omental vessels. Propofol 10(-3) mol litre-1 induced contractions in both arteries and veins attenuated the contraction elicited by U46619, KCl and caffeine in a concentration-dependent manner. The threshold concentrations for the effect of propofol in the artery were: 10(-5) mol litre-1 (U46619, caffeine) and 10(-4) mol litre-1 (KCl); and in the vein, 10(-5) mol litre-1 (U46619) and 10(-4) mol litre-1 (KCl, caffeine). We conclude that propofol at lower concentrations appeared to primarily attenuate contraction involving release of cellularly sequestered calcium. At higher concentrations (> 10(-4.5) mol litre-1), propofol appeared to affect contraction involving extracellular or intracellular calcium fluxes similarly.

Effects of propofol on desipramine-sensitive [3H]-noradrenaline uptake kinetics in rat femoral artery.

BACKGROUND: The intravenous anaesthetic propofol inhibits the neuronal uptake of noradrenaline (uptake1) from the vascular sympathetic neuromuscular junction, resulting in an enhancement of the sympathetic neurotransmission. This could be important for maintenance of blood pressure during propofol anaesthesia. The aim of the present study was to determine how propofol influences the kinetics of uptake1. METHODS: Isolated segments of rat femoral arteries were incubated with [3H]-noradrenaline in the presence or absence of propofol and the radioactivity taken up was measured in a scintillation counter. The uptake1 inhibitor, desipramine, was used to delineate the specific neuronal uptake. RESULTS: Desipramine and 10 microM propofol significantly reduced the uptake in segments incubated with 0.1 microM [3H]-noradrenaline. Propofol at 1 microM and 100 microM did not affect the uptake. Non-linear regression analysis of specific uptake yielded Km 0.50 microM, Vmax 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 microM) increased the Km value and propofol (10-100 microM) increased the Vmax value concentration-dependently, while the Hill coefficient was not affected. CONCLUSION: Propofol seems to have a biphasic effect on the uptake of noradrenaline in the vascular sympathetic neuromuscular junction. At lower propofol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher propofol concentrations by an increase in the efficacy of the uptake.

Characteristics of contractile 5-HT receptors in isolated human omental arteries: presence of 5-HT1 and 5-HT2 receptors.

5-Hydroxytryptamine (5-HT) has a variety of biological effects, e.g. it induces and modulates vascular smooth muscle activity. The effects are mainly mediated via a hetergenous group of 5-HT receptor subtypes. In order to elucidate the 5-HT receptor mechanisms in the human splanchnic circulation, in vitro studies were carried out on omental arteries obtained from patients undergoing abdominal surgery. Four 5-HT receptor agonists with different selectivity all induced concentration-dependent contraction (potency and order of potency indicated): 5-HT (non-selective; 6.12 +/- 0.14)=sumatriptan (5-HT1; 6.32 +/- 0.07) > alpha-methyl-5-HT (5-HT2; 5.41 +/- 0.05) > 2-methyl-5-HT (5-HT3; < or =4.46+/-0.05). The 5-HT1/5-HT2 receptor antagonist methiothepin antagonised the contraction induced by 5-HT, sumatriptan, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT2 receptor antagonist ketanserin antagonised the contraction induced by 5-HT, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT3 receptor antagonist tropisetron did not antagonise the contraction elicited by 2-methyl-5-HT. The results suggest that 5-HT-induced conataction in human omental arteries involves both 5-HT1 and 5-HT2, but maybe not 5-HT3-receptors.

Relaxant effects of propofol on human omental arteries and veins.

We have investigated the relaxant effects of propofol on smooth muscle tension in human omental arteries and veins to determine if endothelium-related mechanisms are involved. Isolated vessel segments were precontracted with endothelin-1 and propofol was added cumulatively (10(-7)-10(-4) mol litre-1). In both artery and vein segments, propofol induced relaxation, which was not dependent on an intact endothelium. Relaxation was reduced when the extracellular K+ concentration was increased and in the presence of tetraethylammonium chloride (TEA). In intact segments, N-nitro-L-arginine methyl ester (L-NAME), indomethacin, glibenclamide, 4-aminopyridine, clotrimazole and atropine did not affect the concentration-response curve of propofol. This indicates that propofol relaxes human omental arteries and veins in an endothelium independent manner, and that hyperpolarization caused by activation of the K+ channel, BKCa, may be involved.

Effects of propofol on isolated human pial arteries.

BACKGROUND: The intravenous anaesthetic propofol has been reported to increase cerebral vascular resistance in vivo. The underlying mechanisms are not fully understood, but may include effects on metabolism and direct effects on the vascular smooth muscle. The present study was designed to evaluate the direct effects of propofol on human pial arteries. METHODS: We investigated the direct effect of propofol (10(-6)-10(-4) M) on isolated human pial arteries at basal tension as well as the influence on contractions induced by 5-hydroxytryptamine, prostaglandin F2alpha, noradrenaline and potassium chloride. RESULTS: Propofol did not change the basal tension. Propofol at 10(-6) and 10(-5) M did not affect the concentration-response curves of any of the contractile agents tested. Propofol at the supraclinical concentration 10(-4) M reduced the contractions induced by all contractile agents. CONCLUSION: Propofol reduces the tone of human pial arteries in vitro at supraclinical concentrations, but has no effect on the tone at clinically relevant concentrations.

Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins.

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.