Sickness benefit cuts mainly affect blue-collar workers.

AIMS: To analyse the impact of sick-pay cuts on the use of sickness absence by employees of different socioeconomic groups. In 2009 cuts in sick pay were implemented in reaction to an economic crisis in Estonia. METHODS: Nationwide health survey data from the years 2004, 2006, 2008, and 2010 were used to evaluate sickness absence among blue-collar and white-collar workers. The dataset comprised 7,449 employees of 20-64 years of age. Difference in prevalence of absentees before and after the reform was assessed using the chi-squared test. Odds ratios (OR) for sickness absence were calculated in a multivariate logistic regression model. RESULTS: After the reform, the proportion of blue-collar workers who had been on sick leave decreased from 51% to 40% (p<0.001) and among white-collar employees from 45% to 41% (p=0.026). This reduction had a similar pattern in all the subgroups of blue-collar employees as stratified according to gender, age, self-rated health, and presence of chronic disease, especially among those with low incomes; in white-collar employees it reached statistical significance only in those with good self-rated health (p=0.033). In a multivariate model the odds of having lower sickness absence were highly significant only in blue-collar employees (OR 0.63; 95% confidence interval 0.51-0.77, p<0.001). CONCLUSIONS: The cuts in sickness benefits had a major impact on the use of sickness absence by blue-collar employees with low salaries. This indicates that lower income was a major factor hindering the use of sick leave as these employees are most vulnerable to the loss of income.

Risk factors for sickness absence among Estonian employees.

BACKGROUND: During the last decade, sickness absence rates in Estonia have reached the level of Nordic countries. This places Estonia in a group of countries with the highest absence rate in the European Union. Unlike Nordic countries, factors associated with sickness absence have not been studied in Estonia. AIMS: To investigate which work-related, individual and health factors, other than current illness, influence sickness absence among Estonian paid employees. METHODS: The study population consisted of 2941 employees who completed an Estonian Health Interview Survey conducted in 2006. Multiple logistic regression analysis was performed to explore associations between individual, health and work-related factors and recent sickness absence. RESULTS: Sickness absence was significantly associated with poor self-rated general health (OR = 1.82; 95% CI = 1.34-2.48), presence of chronic disease (OR = 1.66; 95% CI = 1.21-2.27), lower education (OR = 1.59; 95% CI = 1.20-2.12) and job dissatisfaction (OR = 1.74, 95% CI = 1.23-2.26) in the final multivariate model after adjustment for age and gender conclusions: Most sickness absence risk factors revealed by previous studies were only moderately associated with sickness absence in the Estonian working population. In contrast to Nordic countries, there was no gender difference or age gradient. Among workplace risk factors, job dissatisfaction was most strongly associated with sickness absence.

Measuring burden of disease in Estonia to support public health policy.

BACKGROUND: Many countries have an overview on mortality and morbidity but few have performed contextualized national burden of disease studies. The objective of the present study is to provide a first set of national and sub-national burden of disease estimates for Estonia. Further, we present the causes and age-gender distribution of the burden. We conclude with the description of result uptake and impact of the study in Estonian public health policy arena. METHODS: A burden of disease estimation procedure modified for best fit to country situation was used. That included disease classification reflecting Estonian disease profile, national disease severity assessments, mortality and morbidity prevalence data. Calculations were performed on national and sub-national levels. RESULTS: Estonian population lost 446 361 (327/1000 persons) disability adjusted life-years in 2002. Premature mortality caused majority of the burden and cardiovascular diseases, external causes (e.g. suicide and injuries) and cancers were main sources of burden. Working age population (16-64 years) shouldered 60% of the burden. Sub-national levels of burden range from 114 to 725 disability adjusted life-years per 1000 persons and are correlated to regional socioeconomic development. CONCLUSION: Cardiovascular disease and injuries, premature mortality, working age population, male and people from economically less developed regions should be the priority targets for public health interventions. Estonian main public health strategies now address burden of disease concerns highlighted by our study.

Costs of asthma treatment in Estonia.

BACKGROUND: The aim of this study was to describe the distribution of the direct costs of asthma in Estonia by the type of treatment received and to differentiate the costs by age of patients. METHODS: Data were obtained from the databases of national health insurance offices. Persons who had been in a hospital or visited a doctor because of asthma and who also purchased anti-asthmatic drugs during 1997 were identified. The bills of all direct costs of health insurance for each asthma patient could thus be summarised. The data on all purchases of drugs were used to follow the patterns of drug treatment of asthma. RESULTS: The mean annual treatment costs of one asthma patient were 118 EUR. The costs of hospital care accounted for 27%, costs of ambulatory care for 20% and costs of pharmacotherapy for 53% of all treatment costs. Beta-agonists and corticosteroids for inhalation accounted for more than 80% of prescriptions and 90% of pharmacotherapy costs in patients under 45 years. The users of oral corticosteroids had twice as high per capita annual asthma treatment costs as compared to non-users. CONCLUSIONS: The frequency of out-patient visits, hospital admissions, number of prescriptions, total costs and costs of pharmaceuticals increased in parallel with age. The total estimated direct costs of asthma diagnosis and treatment during 1997, as extrapolated from the study population, were 2.1 million EUR, and accounted for 1.4% of direct health care costs in Estonia.

Comparative bioavailability of three different preparations of rifampicin.

OBJECTIVE: To study the relative bioavailabilities of two generic rifampicin preparations with Rimactane. METHOD: Each of nineteen healthy volunteers received a single oral dose of 600 mg of rifampicin in an open cross-over randomised three-way single-dose design with a washout period of 7 days between each doses. Plasma concentrations of rifampicin were determined by HPLC. In vitro dissolution profiles of the same drugs were determined and compared with human bioavailability study results. RESULTS: No statistically significant difference was found in main bioavailability parameters between Rimactane and generic preparations studied. Both generic preparations also fulfilled the bioequivalence criteria based on the 90% confidence intervals. There was a good correlation between in vivo and in vitro results: faster dissolution time corresponded to the lower Tmax value; lower percentage of released compound to the lower AUC value. Significant intersubject variations were found in main bioavailability parameters; significant negative correlation was found between average AUC values and body weight of the volunteer. CONCLUSION: All three products were bioequivalent. Our results also suggest the suitability of one-compartmental model with lag time, first order input and first order output to describe the kinetics of rifampicin.

Antibiotic use in 3 European university hospitals.

The use of antibiotic drugs was studied in university teaching hospitals in Tartu, Estonia, Huddinge, Sweden and Badajoz, Spain. Data on drug deliveries to hospital wards during 1992 are presented in defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days). In addition, the time trends of antibiotic use in Tartu University Hospital from 1992 to 1995 are shown. The total amount of antibiotic drugs used for systemic treatment in 1992 was similar in the 3 hospitals, 41 DDD/100 bed-days in Tartu vs. 51 DDD/100 bed-days in Badajoz and 47 DDD/100 bed-days in Huddinge. The antibiotics used most frequently were tetracyclines and aminoglycosides in Tartu, broad-spectrum penicillins and cephalosporins in Badajoz and narrow-spectrum penicillins and cephalosporins in Huddinge. Injectable preparations accounted for one-half of the antibiotics used. Among the medical departments, the total use of antibiotics varied up to 3-fold (from 19 to 61 DDD/100 bed-days), less than among the surgical departments (18-94 DDD/100 bed-days). The frequency of antibiotic use was very similar in departments of similar profile in the 3 hospitals (i.e. in departments of neurology, urology, etc.). The use of antibiotic drugs in intensive care units was twice as high in Huddinge (243 DDD/100 bed-days) as in Badajoz (106 DDD/100 bed-days) and Tartu (135 DDD/100 bed-days) in 1992. In conclusion, the international differences in the use of antibiotics in hospital were not in the frequency of use, but in the predominant prescription preferences in the hospital.

Drug use in Estonia in 1994-1995: a follow-up from 1989 and comparison with two Nordic countries.

OBJECTIVE: To determine the patterns of drug use in Estonia for the years 1989 and 1994 1995, i.e. for the years before and after the pharmaceutical services in the country changed from a state monopoly to a competitive market. METHODS: The wholesale data from Estonia and the defined daily doses methodology were used. For comparison, national statistics on medicines from Finland and Sweden for the years 1994-1995 are shown. RESULTS: The general sales of drugs in Estonia decreased almost twofold in all major pharmacological groups from 1989 to 1994 and subsequently increased by 10%-30% in 1995. Substantial differences in patterns of drug use between Estonia and the two Nordic countries were observed. The amount of prescription-only medicines used in Estonia was approximately 25% of that used in Finland and Sweden. The amount of over-the-counter drugs used was 61% of that used in Finland and 58% of that used in Sweden. In the drug use patterns in Estonia, some common trends can be noted: (1) persistent traditions, such as the low use of diuretics, beta-blockers, antithrombotics and inhalant anti-asthmatic drugs; (2) changes in prescription preferences--central anti-adrenergic drugs, pyrazolones, aminoglycosides and barbiturates are being replaced by calcium channel blockers and angiotensin-converting-enzyme inhibitors, propionic acid derivatives, cephalosporins and benzodiazepines, respectively; (3) rapidly increasing use of drugs not prescribed in the 1980s, such as hormonal contraceptives, opioids and antiulcer drugs, which strongly improves the quality of pharmacotherapy in Estonia. CONCLUSION: The general trends in Estonia and the two Nordic countries are similar--the use of newer and more effective drugs is increasing and that of older ones decreasing. The changes are more rapid in Estonia than in Finland and Sweden, but, because of a short observation period, the use of newer drugs not yet prevailing. The international differences in drug utilization observed in this study may possibly be related mainly to the prescription preferences (e.g. therapeutic traditions) and less dependent on the respective health care systems (e.g. reimbursement schemes) and economic state of the country.

Debrisoquin and S-mephenytoin hydroxylation phenotypes and CYP2D6 genotypes in an Estonian population.

The polymorphisms of debrisoquin (CYP2D6) and S-mephenytoin (CYP2C19) hydroxylation were studied in 210 unrelated healthy native Estonians by coadministration of mephenytoin and debrisoquin or dextromethorphan. Among the 210 volunteers 21 (10%) were poor metabolizers of debrisoquin/dextromethorphan and two (0.95%) were poor metabolizers of S-mephenytoin. By pooling these data with an earlier study on 156 Estonians, the prevalences of poor metabolizers of debrisoquin/dextromethorphan and poor metabolizers of S-mephenytoin were 7.6% and 2.2%, respectively. The CYP2D6 genotype of 151 subjects was analysed by allele-specific PCR amplification for the defect alleles CYP2D6A and CYP2D6B. All poor metabolizers of debrisoquin carried two defect CYP2D6-alleles. The phenotype (extensive or poor metabolizer) was in all subjects correctly predicted by the genotype. The frequencies of the defect alleles CYP2D6B and CYP2D6A among these 151 subjects (including 14 poor metabolizers-9.3%) were 21.5% and 2.3%, respectively. DNA from 6 subjects with very high CYP2D6 activity (debrisoquin MR < 0.1) was analysed by EcoRI RFLP to identify duplicated or amplified CYP2D6-genes. Two of the subjects were found to carry a duplicated CYP2D6L-gene. In conclusion, the distribution of genetically determined metabolic capacities of CYP2D6 and CYP2C19 in Estonian unrelated subjects did not differ significantly from that in other Caucasian populations. The CYP2D6 phenotype was predicted by PCR-based amplification for the CYP2D6A and CYP2D6B-alleles.

Patterns of drug treatment of schizophrenic patients in Estonia, Spain and Sweden.

1. Patterns of drug treatment and the use of polypharmacy in schizophrenic in-patients were compared and evaluated in the University Teaching Hospitals of Psychiatry in Badajoz, Spain, Huddinge, Sweden, and Tartu, Estonia. 2. The medical records of up to 100 consecutively admitted patients were retrospectively reviewed using a standardized data form. 3. The male patients were significantly younger than females in all study locations, but there were no age differences between the locations. The length of stay was equal for the two series in the same hospital, but considerably longer in Tartu than in Badajoz and Huddinge. 4. The neuroleptic drugs used most commonly in Badajoz and Tartu were similar in prescription frequency and in the doses prescribed, but different from those used in Huddinge. Haloperidol was the most frequently prescribed neuroleptic in Badajoz and Tartu, accounting for one third of all neuroleptic prescriptions. In Huddinge the choice of neuroleptics was more evenly spread over several compounds. Intramuscular injections other than depot preparations were commonly used in Tartu and Badajoz, but not in Huddinge. 5. At least two neuroleptics were prescribed simultaneously on 73% of treatment days in Badajoz and 46% in both Huddinge and Tartu. The average cumulative daily doses of concomitant multiple neuroleptic treatment, expressed in chlorpromazine equivalents, were lower in Huddinge than in the other study locations and higher for male patients in Badajoz and Tartu. 6. Anticholinergics were used together with neuroleptics in 42% of treatment days in Badajoz and 30% in Huddinge as compared with 75% in Tartu. The use of anticholinergics increased in parallel to the increase in the number and the cumulative dose of concomitant neuroleptics in all study locations. 7. About 15% of patients in Badajoz and Tartu, but only 1% in Huddinge, received concomitant treatment with antidepressant drugs. The simultaneous use of antidepressants and benzodiazepines was inversely related to the number and the cumulative dose of neuroleptics in Badajoz and Tartu. In contrast, the cumulative dose and number of neuroleptics were greater, when additional benzodiazepines were prescribed in Huddinge. 8. The study in schizophrenic in-patients revealed that polypharmacy with concomitant multiple neuroleptics, additional anticholinergics and other psychotropics is an international phenomenon.

Changes in the use of antibacterial drugs in the countries of central and eastern Europe.

Use of systemic antibacterial drugs in the countries of central and eastern Europe (CCEE) has been studied using the defined daily doses (DDD) methodology. For the comparison, national wholesale data from Bulgaria, the Czech Republic, Estonia, Hungary, Lithuania, Slovakia, Slovenia and Romania for the years 1989 and 1992 were used, i.e. for the years before and after the rapid sociopolitical changes in these countries. Substantial differences in the patterns of antibacterial drug use between countries as geographically and economically similar as the CCEE were observed. The general sales of antibiotics varied almost twofold among the CCEE and had decreased in most of the CCEE during the study period. The proportion of tetracyclines in the sales of 1992 ranged from 10% in Slovenia to 49% in Estonia, and that of broad-spectrum penicillins from 6% in Estonia to 40% in Slovenia. The use of narrow-spectrum penicillins varied within the range of 4% in Bulgaria to 38% in Slovakia, and had decreased during the study years in all countries. Aminoglycosides accounted for 5-12% of all antibacterials in Bulgaria, Estonia, Lithuania, Romania and Slovakia in the study period, and these countries, with the exception of Slovakia, also had a high consumption of chloramphenicol. In 1992, by far the most popular antiinfectives in the CCEE were doxycycline, ampicillin and co-trimoxazole, which ranked among the top ten drugs in all countries studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphism of debrisoquine and mephenytoin hydroxylation among Estonians.

Debrisoquine and S-mephenytoin hydroxylation polymorphisms were studied in 156 unrelated native Estonians. The hydroxylation phenotypes were assessed by coadministration of mephenytoin with debrisoquine or dextromethorphan. The frequency of the poor metaboliser phenotype of debrisoquine/dextromethorphan was 4.5% (95% confidence interval 1.2-7.8%), and that of mephenytoin was 3.9% (95% confidence interval 0.9-6.9%) among Estonians, which is very similar to what has been reported in other Caucasian populations.

Possibilities for future cooperation within the field of respiratory physiology and pharmacology.

From the viewpoint of clinical research in respiratory diseases the situation seems promising. On one hand, there are a lot of unanswered questions in pulmonology. And on the other, there are possibilities to solve these questions, by the combination of research experience, facilities, patients, and last but not least--individual initiatives. Shortage of money has the positive effect in maintaining the simple and reliable old skills in research and clinical practice as there are few sophisticated and expensive apparatus to rely on. The physicians must also be very inventive to help their patients when medical supplies are insufficient. Therefore, success in science and in scientific cooperation is determined by the persons engaged. Finding capable and dedicated people is crucial and the most vital challenge to whatever project. And such people can be found on both sides of the Baltic Sea. In conclusion, this short description of differences between the Baltic States and the Nordic countries could, give some clues for future cooperation. Based on the well known key-lock model of pharmacology, team-work between different talents will give results not attainable individually. When all think alike, nobody thinks.

Bioavailability of two Soviet sustained-release theophylline formulations in comparison with TheoDur.

The pharmacokinetic parameters of two theophylline preparations of Soviet origin (Theobiolongas and Theopaek) were compared with the reference preparation TheoDur. The three sustained-release preparations were administered in a single oral dose (400 mg) to healthy volunteers. Blood samples were drawn over 36 hr and plasma concentrations of theophylline were measured by HPLC. Significant differences in the pharmacokinetic parameters were observed between the drugs. Compared to TheoDur, the two Soviet drugs, Theobiolongas and Theopaek, had lower bioavailability (86% and 82%, respectively), and higher rate of absorption. An 8-hr dosing interval should be preferred for Theobiolongas and Theopaek while twice-daily administration appears to be appropriate for these preparations only in exceptional cases.

The use of drugs in Estonia compared to the Nordic countries.

Wholesale data from Estonia covering all drug supplies during the period 1983-1989 have been studied using the defined daily dose (DDD) methodology. The use of all major pharmacological groups was compared with the corresponding statistics from the Nordic countries. The patterns of drug use showed large differences between the Nordic countries and Estonia. Many drugs were used in large quantities in Estonia although they are no longer considered to be first-line medications in the Nordic countries because of their high risk to benefit ratio. These included the pyrazolones (phenylbutazone, aminophenazone), chloramphenicol, aminoglycoside antibiotics, and Rauwolfia alkaloids. On the other hand, several groups of effective drugs were available in Estonia only in limited amounts, including the histamine (H2) receptor antagonists, hormonal contraceptives, beta-adrenoceptor antagonists, angiotensin converting enzyme inhibitors, and cephalosporins. There were also differences in the use of non-steroidal anti-inflammatory drugs, blood pressure lowering agents, and anti-asthmatic drugs. Amongst the factors influencing drug usage it appears that economic status, the ordering and invoicing routines of the pharmaceutical services, and therapeutic traditions were the main reasons for the differences found.

Correlation between exploratory activity in an elevated plus-maze and number of central and peripheral benzodiazepine binding sites.

Two groups of rats were selected from a small animal population on the basis of their exploratory activity in an elevated plus-maze model of anxiety. One group had a considerably lower and the other one a higher exploratory activity than the average total population. These subgroups were termed "anxious" and "non-anxious", respectively. In both groups central benzodiazepine binding sites in various brain structures were labelled with 3H-flunitrazepam. Peripheral benzodiazepine binding sites labelled in vitro with different tritiated ligands were also studied in several peripheral organs including blood platelets and lymphocytes. "Anxious" animals had a significantly lower number of 3H-flunitrazepam binding sites in the cerebral cortex but not in the hippocampus and cerebellum. In this subgroup 3H-Ro 5-4864 binding to peripheral benzodiazepine recognition sites was also lower than in the other one in adrenals, kidneys, platelets and lymphocytes. In the heart no differences of 3H-Ro 5-4864 binding between subgroups studied were found. Although in "anxious" rats 3H-diazepam and 3H-PK 11195 binding was significantly lower only in lymphocytes, a somewhat decreased binding to these ligands was also present in platelets. No significant differences in the affinity were found between the two groups throughout the experiments described. The results indicate that behavioral anxiety in rats is correlated not only with the lower number of central benzodiazepine receptors but also with a lower density of peripheral benzodiazepine binding sites in several peripheral organs including platelets and lymphocytes.

Rats with anxious or non-anxious type of exploratory behaviour differ in their brain CCK-8 and benzodiazepine receptor characteristics.

Rats with high and low exploratory activity in an elevated plus-maze model of anxiety were separated into subgroups termed 'non-anxious' and 'anxious' respectively according to the number of sectors the animals crossed and the total amount of time they spent in the open part of the plus-maze. The binding parameters of benzodiazepine and cholecystokinin octapeptide (CCK-8) receptors in frontal cortex and hippocampus of selected animals were studied and compared to an animal group representing the total mean scores and to home-cage controls. It was established that anxious rats had a significantly lower number of benzodiazepine receptors in frontal cortex as compared to non-anxious animals and in hippocampus as compared to home-cage controls. There was also a decreased number of CCK-8 receptors in hippocampus of anxious rats as compared to the non-anxious and control groups. Non-anxious animals had a significantly lower number of CCK-8 receptors in frontal cortex than anxious and control rats. Acute treatment of rats with anxiogenic benzodiazepine inverse agonist FG 7142 (10 and 20 mg/kg) did not influence benzodiazepine binding in brain regions under investigation but caused upregulation of CCK-8 receptor binding in frontal cortex. On the other hand, CCK-8 analogues caerulein and pentagastrin, administered in doses which inhibit exploratory activity in plus-maze (100 or 500 ng/kg respectively), decreased the number of benzodiazepine binding sites in rat frontal cortex if injected intraperitoneally but did not affect CCK-8 binding. The present findings indicate that benzodiazepine and CCK-8 receptor binding characteristics in brain undergo rapid and behaviourally specific changes during stressful events.

Thymopentin antagonizes stress-induced changes of GABA/benzodiazepine receptor complex.

Intraperitoneal administration of thymopentin, a thymopentin II-derived pentapeptide, had no stable and evident effect in the two anxiety models (elevated plus-maze and licking-conflict test) studied. However, in the elevated plus-maze test thymopentin antagonized the behavioral effects of DMCM, a beta-carboline derivative with anxiogenic properties. Further, it was demonstrated that the licking-conflict test procedure itself produced a significant elevation of plasma corticosterone levels, increased the number of [3H]flunitrazepam and decreased the number of [3H]muscimol binding sites in rat hippocampus. The forced-swimming stress similarly to the licking-conflict test also caused an increase in hippocampal [3H]flunitrazepam binding sites. Although ineffective behaviorally in the tests for anxiety, thymopentin pretreatment effectively reversed the changes in corticosterone levels caused by the licking-conflict test. Moreover, it normalized the changed number of benzodiazepine and GABA receptors after stressful stimuli. It is well known that not all anxiolytic drugs (i.e. buspirone) are equally active in behavioral tests for anxiety. According to our data we propose that thymopentin has stress-protective activity. As in vivo and in vitro thymopentin did not change [3H]-flunitrazepam and [3H]muscimol binding, the direct effect of this peptide on the GABA-benzodiazepine-Cl- ionophore receptor complex is unlikely. The action of this peptide on GABA release and/or metabolism can be suggested.

Stress-protection action of beta-phenyl(GABA): involvement of central and peripheral type benzodiazepine binding sites.

Forced swimming stress caused a significant increase in the density of central type benzodiazepine binding sites in rat cerebral cortex and hippocampus. The number of peripheral type benzodiazepine binding sites was also enhanced on blood platelets. The affinity of neither central nor peripheral type benzodiazepine binding sites was changed considerably after swimming stress. Pretreatment of rats with beta-(phenyl)GABA (100 mg/kg), a GABAB agonist, almost completely eliminated the described changes of the both types of benzodiazepine binding sites caused by swimming stress. In an elevated plus-maze model of anxiety beta-(phenyl)GABA itself was inactive but like diazepam effectively counteracted the behavioural effects of DMCM, a beta-carboline derivative with anxiogenic properties. The possible involvement of benzodiazepine receptors in the mechanism of action of beta-(phenyl)GABA is discussed.