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.

Sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis.

AIMS: To study sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis (PSC). METHODS: One hundred and twelve biopsy specimens (that is, 56 pairs) from 44 patients with PSC, confirmed by cholangiography, were evaluated blindly. Six different features, qualitative grading of four other features and staging according to Ludwig were assessed. RESULTS: Quantitative sampling variability was confined mainly to just one grade or stage, although 11% (six of 56) of the biopsy specimen pairs differed by more than one stage (7% (one of 15) in pairs > 2 cm in length). Qualitative sampling variabilities were between 18 and 71%. Advanced disease (stages 3 or 4) was missed in 40% (two of five) of the biopsy specimens while cirrhosis was missed in 37%. CONCLUSION: Paired liver biopsy specimens should be taken in clinical studies of PSC using liver histology for evaluation or prognosis.

Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice.

In this intervention study, we have investigated if hypertensive patients are more sensitive to liquorice-induced inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 2 than normotensive (NT) subjects and if the response depends on gender. Healthy volunteers and patients with essential hypertension (HT), consumed 100 g of liquorice daily, for 4 weeks, corresponding to a daily intake of 150 mg glycyrrhetinic acid. Office, 24-h ambulatory blood pressure (BP) and blood samples were measured before, during and after liquorice consumption. Effect on cortisol metabolism was evaluated by determining the urinary total cortisol metabolites and urinary free cortisol/free cortisone quotient (Q). The mean rise in systolic BP with office measurements after 4 weeks of liquorice consumption was 3.5 mmHg (p<0.06) in NT and 15.3 mmHg (p=0.003) in hypertensive subjects, the response being different (p=0.004). The mean rise in diastolic BP was 3.6 mmHg (p=0.01) in NT and 9.3 mmHg (p<0.001) in hypertensive subjects, the response also being different (p=0.03). Liquorice induced more pronounced clinical symptoms in women than in men (p=0.0008), although the difference in the effect on the BP was not significant. The increase in Q was prominent (p<0.0001) and correlated to the rise in BP (p=0.02). The rise in BP was not dependant on age, the change in plasma renin activity or weight. We conclude that patients with essential HT are more sensitive to the inhibition of 11 beta-HSD by liquorice than NT subjects, and that this inhibition causes more clinical symptoms in women than in men.

Liquorice-induced rise in blood pressure: a linear dose-response relationship.

To clarify the dose-response and the time-response relationship between liquorice consumption and rise in blood pressure and explore the inter-individual variance this intervention study was designed and executed in research laboratories at University hospitals in Iceland and Sweden. Healthy, Caucasian volunteers who also served as a control for himself/herself consumed liquorice in various doses, 50-200 g/day, for 2-4 weeks, corresponding to a daily intake of 75-540 mg glycyrrhetinic acid, the active substance in liquorice. Blood pressure was measured before, during and after liquorice consumption. Systolic blood pressure increased by 3.1-14.4 mm Hg (P < 0.05 for all), demonstrating a dose-response but not a time-response relationship. The individual response to liquorice followed the normal distribution. Since liquorice raised the blood pressure with a linear dose-response relationship, even doses as low as 50 g of liquorice (75 mg glycyrrhetinic acid) consumed daily for 2 weeks can cause a significant rise in blood pressure. The finding of a maximal effect of liquorice after only 2 weeks has important implications for all doctors dealing with hypertension. There does not seem to be a special group of responders since the degree of individual response to liquorice consumption followed the normal distribution curve.

Ischemic heart disease and epilepsy: two major causes of out-hospital natural death in male alcoholics.

The objectives of this research were to study the distribution of in- and out-hospital deaths and causes of death in male alcoholics and in particular to analyze obscure cases. In a population-based sample of 1123 men treated in one detoxification unit during 1986-1989, 97 patients with alcohol dependence (DSM-III-R) died < or = 1 year after in-hospital detoxification. In each case, the cause and the manner of death were assessed by scrutiny of information in hospital and autopsy records, toxicological examinations, and police reports. The results were that 71 of the 97 men died outside hospital. The overall autopsy rate was 89%. Ischemic heart disease accounted for 18 out of 41 evaluable natural out-hospital deaths. Epileptic seizures were judged to be the cause of death in five cases and could also have contributed to seven out of eight obscure out-hospital deaths. Ethanol in blood or urine was detected in 19 of the 23 deaths attributed to trauma or intoxication, whereas only four out of the 18 out-hospital deaths from ischemic heart disease were ethanol-positive. It was concluded that early detection and adequate treatment of ischemic heart disease and epilepsy might improve prognosis in patients with alcohol dependence. The use of clinical information could be of crucial importance in evaluating possible causes of death, especially in obscure cases.

Elevation of cytokines in peritoneal fluid and blood in patients with liver cirrhosis.

BACKGROUND/AIMS: Liver cirrhosis, described as the endstage of a necroinflammatory process, is often accompanied by ascites formation. The rationale for this study was the hypothesis that patients with liver cirrhosis have a low-grade chronic inflammatory response, which leads to an increased amount of proinflammatory cytokines accumulated in ascites. Twenty-five patients with liver cirrhosis complicated by ascites and twelve healthy volunteers were prospectively included in the study. METHODOLOGY: Ascites and blood samples from the patients were obtained for analysis of inflammatory cytokines using enzyme-linked immunosorbent assay methodology. Blood samples were taken from the healthy volunteers to obtain reference values. RESULTS: Plasma and ascites concentrations of interleukin-1alpha, interleukin-6, and tumor necrosis factor-alpha were significantly elevated in the patients compared with plasma levels in the group of healthy controls. Significant elevation of interleukin-10 concentrations was found in ascites but not in plasma in the patients. There was no significant difference in interleukin-10 levels between patient and control plasma. CONCLUSIONS: The findings suggest that elevated cytokine concentrations in ascites and serum could perpetuate an inflammatory reaction that may be a source of preservation of an ongoing systemic inflammatory reaction. This may contribute to the maintenance, and even progress, of the liver dysfunction, leading to exaggerated ascites development.

[Therapeutic program for ascites. Recommendations from the Swedish Society of Gastroenterology and Gastrointestinal Endoscopy]. / Behandlingsprogram vid ascites. Rekommendationer från Svensk förening för gastroenterologi och gastrointestinal endoskopi.

As ascites is related to liver cirrhosis in 80% of the patients, the present therapeutic guidelines are focused on ascites in liver cirrhosis. A combination of spironolactone and furosemide is recommended as first line therapy in patients with mild to moderate ascites and is effective in 90% of patients. In patients with pronounced or tense ascites, first line treatment is total paracentesis with intravenous infusion of human albumin as colloid replacement. Maintenance therapy for the prevention of recurrent ascites is based on spironolactone with or without furosemide. The indications for peritoneovenous shunt, or transjugular intrahepatic stent-shunt (TIPSS), are limited and only recommended in strictly selected patients with refractory ascites. Ascites in liver cirrhosis is a symptom of advanced liver disease, and liver transplantation should always be considered in eligible patients.

The epidemiology and clinical features of portal vein thrombosis: a multicentre study.

BACKGROUND: Reliable epidemiological data for portal vein thrombosis are lacking. AIMS: To investigate the incidence, prevalence and survival rates for patients with portal vein thrombosis. METHODS: Retrospective multicentre study of all patients registered with the diagnosis of portal vein thrombosis between 1995 and 2004. RESULTS: A total of 173 patients (median age 57 years, 93 men) with portal vein thrombosis were identified and followed up for a median of 2.5 years (range 0-9.7). The mean age-standardized incidence and prevalence rates were 0.7 per 100,000 per year and 3.7 per 100,000 inhabitants, respectively. Liver disease was present in 70 patients (40%), malignancy in 27%, thrombophilic factors in 22% and myeloproliferative disorders in 11%. Two or more risk factors were identified in 80 patients (46%). At diagnosis, 65% were put on anticoagulant therapy. Thrombolysis, TIPS, surgical shunting and liver transplantation were performed in 6, 3, 2 and 8 patients, respectively. The overall survival at 1 year and 5 years was 69% and 54%. In the absence of malignancy and cirrhosis, the survival was 92% and 76%, respectively. CONCLUSIONS: The incidence and prevalence rates of portal vein thrombosis were 0.7 per 100,000 inhabitants per year and 3.7 per 100,000 inhabitants, respectively. Concurrent prothrombotic risk factors are common. The prognosis is variable and highly dependent on underlying disease.