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Abstract Background The aim of our study was to investigate and control an outbreak and identify risk factors for colonization and infection with Serratia marcescens in two departments in Tartu University Hospital. Methods The retrospective case–control study was conducted from July 2005 to December 2006. Molecular typing by pulsed field gel electrophoresis was used to confirm the relatedness of Serratia marcescens strains. Samples from the environment and from the hands of personnel were cultured. Results The outbreak involved 210 patients, 61 (29%) developed an infection, among them 16 were invasive infections. Multivariate analysis identified gestational age, arterial catheter use and antibiotic treatment as independent risk factors for colonization and infection with Serratia marcescens. Molecular typing was performed on 83 Serratia marcescens strains, 81 of them were identical and 2 strains were different. Conclusions Given the occasionally severe consequences of Serratia marcescens in infants, early implementation of aggressive infection control measures involving patients and mothers as well as the personnel is of utmost importance.

Abstract Background About 10-20% of neonates with suspected or proven early onset sepsis (EOS) fail on the empiric antibiotic regimen of ampicillin or penicillin and gentamicin. We aimed to identify clinical and laboratory markers associated with empiric antibiotic treatment failure in neonates with suspected EOS. Methods Maternal and early neonatal characteristics predicting failure of empiric antibiotic treatment were identified by univariate logistic regression analysis from a prospective database of 283 neonates admitted to neonatal intensive care unit within 72 hours of life and requiring antibiotic therapy with penicillin or ampicillin and gentamicin. Variables, identified as significant by univariate analysis, were entered into stepwise multiple logistic regression (MLR) analysis and classification and regression tree (CRT) analysis to develop a decision algorithm for clinical application. In order to ensure the earliest possible timing separate analysis for 24 and 72 hours of age was performed. Results At 24 hours of age neonates with hypoglycaemia ≤ 2.55 mmol/L together with CRP values > 1.35 mg/L or those with BW ≤ 678 g had more than 30% likelihood of treatment failure. In normoglycaemic neonates with higher BW the best predictors of treatment failure at 24 hours were GA ≤ 27 weeks and among those, with higher GA, WBC ≤ 8.25 × 109 L-1 together with platelet count ≤ 143 × 109 L-1. The algorithm allowed capture of 75% of treatment failure cases with a specificity of 89%. By 72 hours of age minimum platelet count ≤ 94.5 × 109 L-1 with need for vasoactive treatment or leukopaenia ≤ 3.5 × 109 L-1 or leukocytosis > 39.8 × 109 L-1 or blood glucose ≤ 1.65 mmol/L allowed capture of 81% of treatment failure cases with the specificity of 88%. The performance of MLR and CRT models was similar, except for higher specificity of the CRT at 72 h, compared to MLR analysis. Conclusion There is an identifiable group of neonates with high risk of EOS, likely to fail on conventional antibiotic therapy.

Abstract Background With the exception of sexual functioning and weight, social and behavioural effects of postmenopausal hormone therapy (HT) have not been reported from trials. This paper reports such results from the EPHT-trial in Estonia. Methods A randomized trial, with a blind and non-blind sub-trial in Estonia. From 1999–2001, 1778 women were recruited. The mean follow-up was 3.6 years. Women's experiences were asked in the first and final study year by mailed questionnaires (74 and 81% response rates). Comparisons of the groups were made by cross-tabulation and logistic regression, adjusting for age. Results There were no differences between the HT and non-HT groups in regard to being employed, the extent of social involvement or marital status or opinions on aging. There was no difference in the frequency of free-time exercise, or overweight. Some of the indicators suggested less sexual inactivity, but the differences were small. Conclusion In a trial setting, postmenopausal hormone therapy did not influence work or social involvement or health behaviour. Trial registration ISRCTN35338757

Proportion of normal deliveries is decreasing worldwide. This study analysed operative vaginal deliveries (OVD) and Caesarean sections (CS) with some background factors in Estonia and Finland from 1992 to 2016. Data on all deliveries from 1992 to 2016 were obtained from the Finnish Medical Birth Registry (1 481 160 births) and the Estonian Medical Birth Registry (356 063 births). Time trends were analysed by joinpoint regression, and factors associated with OVD and CS by logistic regression. Odds ratios with 95% CIs were calculated, adjusted for year, maternal age, foetal birthweight, and use of epidural/spinal anaesthesia. One out of four deliveries were operative in Estonia and in Finland by 2016. By 2016, the Estonian CS rate had tripled to 20.9% and the OVD rate had increased by nine times to 5.6%. In Finland, the CS rate increased slightly to 16.4% while the OVD rate nearly doubled to 9.4%. In Estonia, the incidence of OVD was 24% lower (aOR 0.76, 95% Cl 0.74-0.78) and the incidence of CS 9% higher (aOR 1.09, 95% Cl 1.07-1.10) than in Finland. Use of epidural/spinal anaesthesia and foetal birthweight increased the risk of OVD in both countries, maternal age increased the risk of CS in both countries. Even if the CS and OVD rates are different, operative delivery rates may be similar in different countries. Combined analysis of operative deliveries together with background factors gives a better understanding of the trends in birthcare than monitoring CS rates alone., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

A large proportion of the world's population has some form of immunity against SARS-CoV-2, through either infection ('natural'), vaccination or both ('hybrid'). This retrospective cohort study used data on SARS-CoV-2, vaccination, and hospitalization from national health system from February 2020 to June 2022 and Cox regression modelling to compare those with natural immunity to those with no (Cohort1, n = 94,982), hybrid (Cohort2, n = 47,342), and vaccine (Cohort3, n = 254,920) immunity. In Cohort 1, those with natural immunity were at lower risk for infection during the Delta (aHR 0.17, 95%CI 0.15-0.18) and higher risk (aHR 1.24, 95%CI 1.18-1.32) during the Omicron period than those with no immunity. Natural immunity conferred substantial protection against COVID-19-hospitalization. Cohort 2-in comparison to natural immunity hybrid immunity offered strong protection during the Delta (aHR 0.61, 95%CI 0.46-0.80) but not the Omicron (aHR 1.05, 95%CI 0.93-1.1) period. COVID-19-hospitalization was extremely rare among individuals with hybrid immunity. In Cohort 3, individuals with vaccine-induced immunity were at higher risk than those with natural immunity for infection (Delta aHR 4.90, 95%CI 4.48-5.36; Omicron 1.13, 95%CI 1.06-1.21) and hospitalization (Delta aHR 7.19, 95%CI 4.02-12.84). These results show that risk of infection and severe COVID-19 are driven by personal immunity history and the variant of SARS-CoV-2 causing infection., (© 2023. The Author(s).)

Introduction: The number of cesarean sections (CSs) has grown steadily, but the underlying factors driving this increase remain unknown. Data from Medical Birth Registries were retrieved to analyze CS trends in Estonia and Finland during the period 1992-2016., Material and Methods: All births in Estonia (n = 356 063) and Finland (n = 1 437 234) were included. The differences between Estonia and Finland in five-year time periods for the total CS rate, and rates in Robson 1, 2, and 5 groups (R1, R2, R5) were analyzed by logistic regression. Total CS rates were adjusted for birthweight, parity, previous CS, gestational age, singleton pregnancy, cephalic position, induction, mother's age. R1; R2; R5 rates were adjusted for birthweight and mother's age., Results: In Estonia, the proportion of CSs increased from 6.5% to 21.0% and in Finland from 15.1% to 16.8% between 1992 and 2016. In 2016, Estonia and Finland remained within the target value with their R1 + 2 (Estonia 18%; Finland 16%) and R5 (Estonia 59%; Finland 42%) values., Conclusions: Comparing Robson groups in different countries can shed light on divergent CS rates and to improve the quality of perinatal and obstetric care., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

SARS-CoV-2 vaccination is currently the mainstay in combating the COVID-19 pandemic. However, there are still people among vaccinated individuals suffering from severe forms of the disease. We conducted a retrospective cohort study based on data from nationwide e-health databases. The study included 184,132 individuals who were SARS-CoV-2 infection-naive and had received at least a primary series of COVID-19 vaccination. The incidence of BTI (breakthrough infection) was 8.03 (95% CI [confidence interval] 7.95⎼8.13/10,000 person-days), and for severe COVID-19 it was 0.093 (95% CI 0.084⎼ 0.104/10,000 person-days). The protective effect of vaccination against severe COVID-19 remained constant for up to six months, and the booster dose offered an additional pronounced benefit (hospitalization aHR 0.32, 95% CI 0.19⎼0.54). The risk of severe COVID-19 was higher among those ≥ 50 years of age (aHR [adjusted hazard ratio] 2.06, 95% CI 1.25⎼3.42) and increased constantly with every decade of life. Male sex (aHR 1.32, 95% CI 1.16⎼1.45), CCI (The Charlson Comorbidity Index) score ≥ 1 (aHR 2.09, 95% CI 1.54⎼2.83), and a range of comorbidities were associated with an increased risk of COVID-19 hospitalization. There are identifiable subgroups of COVID-19-vaccinated individuals at high risk of hospitalization due to SARS-CoV-2 infection. This information is crucial to driving vaccination programs and planning treatment strategies., (© 2023. The Author(s).)

Aims: The aim of this study was to evaluate the effect of the intervention by proactively sharing a patient's high polygenic risk score (PRS) for coronary artery disease (CAD). Outcomes included: (i) reduction in cardiovascular disease (CVD) risk factors over 12 months; (ii) difference in purchased prescriptions of lipid-lowering and anti-hypertensive drugs between intervention group and control group subjects; and (iii) opinion of the participating physicians and subjects on PRS usefulness., Methods and Results: This randomized controlled trial was conducted among middle-aged subjects with a top 20% CAD PRS in a family medicine setting. Participants were selected from 26 953 Estonian Biobank cohort participants. Subjects were informed and counselled about their PRS score and CAD risk using the visual tool at baseline (Visit I), counselling session (Visit II), and on the final Visit III at 12 months. The primary endpoint was not significantly different. However, the intervention group participants had a significantly higher probability of initiating statin treatment compared with the controls. Their levels of LDL-cholesterol (LDL-C) were significantly decreased compared with baseline on Visit III and significantly lower than in the control group. The vast majority of participating family physicians believe that finding out about genetic risks will affect the subject's lifestyle and medication compliance., Conclusion: Most of our outcome measures were in favour of this intervention. Participants achieved larger changes in cholesterol and blood pressure values. The vast majority (98.4%) of family physicians are interested in continuing to use genetic risk assessment in practice., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Post-acute COVID-19 sequelae refers to a variety of health complications involving different organ systems that have been described among individuals after acute phase of illness. Data from unselected population groups with long-time follow up is needed to comprehensively describe the full spectrum of post-acute COVID-19 complications., Methods: In this retrospective nationwide cohort study, we used data obtained from electronic health record database. Our primary cohort were adults hospitalized with confirmed COVID-19 and matched (age, sex, Charlson Comorbidity Index) unaffected controls from general population. Individuals included from February 2020 until March 2021 were followed up for 12 months. We estimated risks of all-cause mortality, readmission and incidence of 16 clinical sequelae after acute COVID-19 phase. Using a frailty Cox model, we compared incidences of outcomes in two cohorts., Results: The cohort comprised 3949 patients older than 18 years who were alive 30 days after COVID-19 hospital admission and 15511 controls. Among cases 40.3% developed at least one incident clinical sequelae after the acute phase of SARS-CoV-2 infection, which was two times higher than in general population group. We report substantially higher risk of all-cause mortality (adjusted hazard ratio (aHR) = 2.57 (95%CI 2.23-2.96) and hospital readmission aHR = 1.73 (95%CI 1.58-1.90) among hospitalized COVID-19 patients. We found that the risks for new clinical sequalae were significantly higher in COVID-19 patients than their controls, especially for dementia aHR = 4.50 (95% CI 2.35-8.64), chronic lower respiratory disease aHR = 4.39 (95% CI 3.09-6.22), liver disease aHR 4.20 (95% CI 2.01-8.77) and other (than ischemic) forms of heart diseases aHR = 3.39 (95%CI 2.58-4.44)., Conclusion: Our results provide evidence that the post-acute COVID-19 morbidity within the first year after COVID-19 hospitalization is substantial. Risks of all-cause mortality, hospitalisation and majority of clinical sequelae were significantly higher in hospitalized COVID-19 patients than in general population controls and warrant targeted prevention efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tisler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: To analyze how people cope with suicide loss and the implications for primary health care., Background: Previous studies have shown that primary health care will often be an initial source of support for those bereaved by suicide., Methods: We included adult persons who were ready to talk about a suicide completed by a person they knew well (family member or close friend). Participants were recruited via mixed media (television, radio, print, social media, etc.). Altogether, we conducted 37 individual interviews, which were recorded using a dictaphone and lasted from 46 to 158 min. The interviews were transcribed verbatim and analyzed using a content analysis method. The interviewees were mostly women ( n = 27) and family members ( n = 28) of a person who had died by suicide during the years 2012-2018., Findings: We identified two main themes in the data: supporters and barriers in support. Coping with suicide takes time, and support was mostly found among friends and family. Support from GPs was mentioned in the context of diagnosing medical problems and prescribing medicines. Respondents indicated that feeling ashamed and a lack of trust impeded their willingness to seek help from their GP. Unmet needs among the bereaved may increase their risk of diminished mental health outcomes. Thus, primary health care practitioners may have a substantial opportunity to support those who are bereaved by suicide., Conclusion: Primary care providers have an opportunity to provide bereavement support among their patients. Continuing medical education regarding the needs of the bereaved and a coordinated approach among primary care practitioners may be useful to proactively identifying and supporting those in need.

Background: The objective of this study was to describe 12-month mortality following SARS-CoV-2 infection compared with a reference population with no history of SARS-CoV-2., Methods: Nationwide cohort study using electronic health care data on SARS-CoV-2 RNA positive cases (n= 66,287) and reference group subjects (n=254,969) with linkage to SARS-CoV-2 testing and death records., Findings: People infected with SARS-COV-2 had more than three times the risk of dying over the following year compared with those who remained uninfected (aHR 3·1, 95%CI 2·9-3·3). Short-term mortality (up to 5 weeks post-infection) was significantly higher among COVID-19 group (1623·0/10 000) than in the reference group (118/10 000). For COVID-19 cases aged 60 years or older, increased mortality persisted until the end of the first year after infection, and was related to increased risk for cardiovascular (aHR 2 · 1, 95%CI 1 · 8-2 · 3), cancer (aHR 1·5, 95%CI 1·2-1·9), respiratory system diseases (aHR 1·9, 95%CI 1·2-3·0), and other causes of death (aHR 1·8, 95%CI 1·4-2·2)., Interpretation: Increased risk of death from SARS-CoV-2 is not limited to the acute illness: SARS-CoV-2 infection carries a substantially increased mortality in the following 12 months. This excess death mainly occurs in older people and is driven by broad array of causes of death., Funding: Research was carried out with the support of Estonian Research Council (grants PRG1197, PRG198), European Regional Development Fund (RITA 1/02-120) and European Social Fund via IT Academy program., Competing Interests: The authors report no conflicts of interest., (© 2022 The Author(s).)

Background: COVID-19 pandemic has led to overloading of health systems all over the world. For reliable risk stratification, knowledge on factors predisposing to SARS-CoV-2 infection and to severe COVID-19 disease course is needed for decision-making at the individual, provider, and government levels. Data to identify these factors should be easily obtainable., Methods and Findings: Retrospective cohort study of nationwide e-health databases in Estonia. We used longitudinal health records from 66,295 people tested positive for SARS-CoV-2 RNA from 26 February 2020 to 28 February 2021 and 254,958 randomly selected controls from the reference population with no known history of SARS-CoV-2 infection or clinical COVID-19 diagnosis (case to control ratio 1:4) to predict risk factors of infection and severe course of COVID-19. We analysed sociodemographic and health characteristics of study participants. The SARS-CoV-2 infection risk was slightly higher among women, and was higher among those with comorbid conditions or obesity. Dementia (RRR 3.77, 95%CI 3.30⎼4.31), renal disease (RRR 1.88, 95%CI 1.56⎼2.26), and cerebrovascular disease (RRR 1.81, 95%CI 1.64⎼2.00) increased the risk of infection. Of all SARS-CoV-2 infected people, 92% had a non-severe disease course, 4.8% severe disease (requiring hospitalisation), 1.7% critical disease (needing intensive care), and 1.5% died. Male sex, increasing age and comorbid burden contributed significantly to more severe COVID-19, and the strength of association for male sex increased with the increasing severity of COVID-19 outcome. The strongest contributors to critical illness (expressed as RRR with 95% CI) were renal disease (7.71, 4.71⎼12.62), the history of previous myocardial infarction (3.54, 2.49⎼5.02) and obesity (3.56, 2.82⎼4.49). The strongest contributors to a lethal outcome were renal disease (6.48, 3.74⎼11.23), cancer (3.81, 3.06⎼4.75), liver disease (3.51, 1.36⎼9.02) and cerebrovascular disease (3.00, 2.31⎼3.89)., Conclusions: We found divergent effect of age and gender on infection risk and severity of COVID-19. Age and gender did not contribute substantially to infection risk, but did so for the risk of severe disease Co-morbid health conditions, especially those affecting renin-angiotensin system, had an impact on both the risk of infection and severe disease course. Age and male sex had the most significant impact on the risk of severe COVID-19. Taking into account the role of ACE2 receptors in the pathogenesis of SARS-CoV-2 infection, as well as its modulating action on the renin-angiotensin system in cardiovascular and renal diseases, further research is needed to investigate the influence of hormonal status on ACE2 expression in different tissues, which may be the basis for the development of COVID-19 therapies., Competing Interests: The authors have declared that no competing interests exist.

Background: Multimorbidity is associated with physical-mental health comorbidity (PMHC). However, the scope of overlap between physical and mental conditions, associated factors, as well as types of mental illness involved are not well described in Eastern Europe. This study aims to assess the PMHC burden in the Estonian population., Methods: In this population-based cross-sectional study we obtained health claims data for 55 chronic conditions from the Estonian Health Insurance Fund (EHIF) database, which captures data for all publicly insured individuals (n = 1 240 927 or 94.1% of the total population as of 31 December 2017). We assessed the period-prevalence (3 years) of chronic physical and mental health disorders, as well as associations between them, by age and sex., Results: Half of the individuals (49.1% (95% CI 49.0-49.3)) had one or more chronic conditions. Mental health disorders (MHD) were present in 8.1% (8.1-8.2) of individuals, being higher among older age groups, women, and individuals with a higher number of physical conditions. PMHC was present in 6.2% (6.1-6.2) of the study population, and 13.1% (13.0-13.2) of the subjects with any chronic physical disorder also presented with at least one MHD. Dominating MHDs among PMHC patients were anxiety and depression. The prevalence of MHD was positively correlated with the number of physical disorders. We observed variation in the type of MHD as the number of physical comorbidities increased. The prevalence of anxiety, depression, and mental and behavioral disorders due to the misuse of alcohol and other psychoactive substances increased as physical comorbidities increased, but the prevalence of schizophrenia and dementia decreased with each additional physical disease. After adjusting for age and sex, this negative association changed the sign to a positive association in the case of dementia and mental and behavioral disorders due to psychoactive substance misuse., Conclusions: The burden of physical-mental comorbidity in the Estonian population is relatively high. Further research is required to identify clusters of overlapping physical and mental disorders as well as the interactions between these conditions. Public health interventions may include structural changes to health care delivery, such as an increased emphasis on integrated care models that reduce barriers to mental health care., Competing Interests: The authors declare that they have no competing interests.

Objectives: Prevalence estimates for specific chronic conditions and multimorbidity (MM) in eastern Europe are scarce. This national study estimates the prevalence of MM by age group and sex in Estonia., Design: A population-based cross-sectional study, using administrative data., Setting: Data were collected on 55 chronic conditions from the Estonian Health Insurance Fund from 2015 to 2017. MM was defined as the coexistence of two or more conditions., Participants: The Estonian Health Insurance Fund includes data for approximately 95% of the Estonian population receiving public health insurance., Primary and Secondary Outcome Measures: Prevalence and 95% CIs for MM stratified by age group and sex., Results: Nearly half (49.1%) of the individuals (95% CI 49.0 to 49.3) had at least 1 chronic condition, and 30.1% (95% CI 30.0 to 30.2) had MM (2 or more chronic conditions). The number of conditions and the prevalence of MM increased with age, ranging from an MM prevalence of 3.5% (3.5%-3.6%) in the youngest (0-24 years) to as high as 80.4% (79.4%-81.3%) in the oldest (≥85 years) age group. Half of all individuals had MM by 60 years of age, and 75% of the population had MM by 75 years of age. Women had a higher prevalence of MM (34.9%, 95% CI 34.7 to 35.0) than men (24.4%, 95% CI 24.3 to 24.5). Hypertension was the most frequent chronic condition (24.5%), followed by chronic pain (12.4%) and arthritis (7.7%)., Conclusions: Hypertension is an important chronic condition amenable to treatment with lifestyle and therapeutic interventions. Given the established correlation between uncontrolled hypertension and exacerbation of other cardiovascular conditions as well as acute illnesses, this most common condition within the context of MM may be suitable for targeted public health interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to study the mortality and intensity of health care in patients with advanced lung cancer who received systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT)., Methods: A retrospective cohort of patients with lung cancer, who were treated at the North Estonia Medical Centre from 2015 to 2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14- and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment., Results: The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR] = 4.23, 95% CI = 3.60-5.00). During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients. Intensive EOL care in the last 30 days of life is more probable among patients in the SACT group (odds ratio [OR] = 3.58, 95% CI = 2.54-5.04, p <  0.001), especially in those with a stage IV disease (OR = 1.89, 95% CI = 1.31-2.71, p = 0.001). In the SACT group 6.7 and 14.7% of patients died within 14 days and 30 days after the last cycle, respectively., Conclusions: Significant proportion of patients with advanced lung cancer continue to receive intensive care near death. Our results reflect current patterns of EOL care for patients with lung cancer in Estonia. Availability of palliative care and hospice services must be increased to improve resource use and patient-oriented care.

Background: Medication adherence can be divided into primary and secondary adherence. Primary medication non-adherence (PMN) occurs when a patient does not obtain medicine with their initial prescription. Secondary non-adherence measures prescription refills among patients who previously filled their first prescription. While secondary non-adherence has been studied thoroughly, PMN has been assessed less extensively, due to lack of available data. Estonian ePrescription system might prove a valuable tool for this., Objectives: The aim of this study was to evaluate PMN and the interval between prescribing and dispensing of medicines using the Estonian ePrescriptions database to establish its potential use for this purpose and for other qualitative drug utilization research measures. Osteoporosis medicines were used as an example., Methods: The Estonian Prescription Centre was used to evaluate if patients purchase medicines after initial prescription of osteoporosis medicine. Prescriptions from 2012 to 2015 of all patients over 18 were included. PMN was defined as the first prescription not being dispensed before it expired (60 days). The rate of PMN was calculated., Results: Estonian ePrescription System enabled fast evaluation of PMN of osteoporosis patients based on data about prescribing, dispensing and time intervals in-between. Of patients who started osteoporosis treatment 13.1% were primary non-adherent. Of primary non-adherent patients 42% still started treatment at some point during the study. Of patients who did purchase their first prescription 80.4% did so within a week and 95% within 25 days., Conclusion: The Estonian ePrescription system is a useful tool for monitoring PMN. The PMN of osteoporosis medicines was identified as lower than previously reported. More similar type of studies about other groups of medicines would be needed to understand the pattern of PMN and give valuable information to healthcare specialists about how to increase initiation of treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Isotretinoin is an effective treatment for severe acne; no alternative treatment has an equal therapeutic effect. The teratogenic effects of isotretinoin can be avoided, and numerous recommendations and regulations are in force to minimize the risk of pregnancy during treatment., Objectives: To describe isotretinoin prescription patterns for women aged 15-45 years, assess the concomitancy of isotretinoin and contraceptive use, and determine the rate of potential isotretinoin-exposed pregnancies in Estonia., Methods: This retrospective, nationwide, population-based, cohort study derived data from national health insurance databases and included female patients aged 15-45 years in Estonia for whom one or more prescriptions for isotretinoin were dispensed between 2012 and 2016. The main outcome was the proportion of women who used systemic isotretinoin and had a concomitant record of (hormonal or intrauterine) contraception use covering the isotretinoin treatment period when pregnancy is contraindicated., Results: Of the 2792 women aged 15-45 years filling an isotretinoin prescription, 15.7% (95% CI 14.4-17.1) had full and 13.9% (95% CI 12.7-15.3) partial (not covering the whole period during which pregnancy is contraindicated) contraceptive coverage. The risk for potential isotretinoin-exposed pregnancy was 3.6 (95% CI 2.0-7.0) per 1000 treated women over the 5-year observation period. The odds for full coverage with effective contraception increased with the age of the patient, with the duration of isotretinoin treatment and over the period of observation., Conclusion: Our study adds to the existing literature documenting limited compliance with pregnancy prevention programs for isotretinoin-containing products, and calls for program assessment to identify whether new measures should be taken or whether weaknesses in policy or implementation can be corrected.

Osteoporosis medicines reduce osteoporotic fractures. There is a very strong negative correlation between the consumption of medicines and the price of an average daily dose indicating that affordability is a key factor that could increase consumption of antiosteoporotic medicines and, through that, reduce fractures., Purpose: Osteoporosis is a major cause of morbidity and mortality in the modern world. Our study aims to describe the trends in incidence of hip fractures in relation to drug utilization patterns and the average price of antiosteoporotic medicines in Estonia., Methods: Data on hip fractures was obtained from the medical claims database of Estonian Health Insurance Fund (EHIF). Consumption and price data was obtained from the Estonian State Agency of Medicines (SAM).Consumption is presented using WHO defined daily doses methodology, and the prices reflect the average wholesale price of medicines., Results: From 2004 to 2010 there was a non-significant increasing trend in standardized hip fracture incidence in Estonia, but from 2010 to 2015, the trend turned to a significant decrease of 4.5% per year. The consumption of osteoporosis medication increased significantly from 2004 to 2009 by yearly average of 41.2%. After 2009, the consumption levelled. On contrast, the average price of one daily dose of osteoporosis medication decreased significantly from 2004 to 2009 by 16.9% per year and the decrease also levelled after 2009. This gives a very strong negative correlation of -0.93 (p < 0.001) between the consumption of antiosteoporotic medication and the average price of a daily dose of medication during the study period., Conclusions: The statistically significant decline of standardized incidence of hip fractures from 2010 onward could at least in part be the result of the high increase in consumption of antiosteoporotic medicines which in turn is strongly negatively correlated with the average price of osteoporosis medicines.

Some patients do not take medicines as they are supposed to. Our research showed that in Estonia, one fifth of patients did not start treatment with osteoporosis medicines and only 20% used the medicines for at least 3 years as they should. This induces unnecessary costs to the healthcare system., Purpose: Medication non-adherence is the number one reason for not obtaining the expected clinical effect of medicines. With osteoporosis treatment, it has been shown that both implementation of treatment and persistence influence the risk of fractures significantly. Long-term adherence to medication in Estonia is to be determined with this study., Methods: A 15-year retrospective study was carried out in order to establish initiation, implementation, and persistence of Estonian patients. All new users of osteoporosis medicines were analyzed for all prescriptions they received during the study period. Sufficient adherence to treatment was defined as a patient being dispensed 80% or more prescribed doses for at least 1 year., Results: The study period was from 2001 to 2015. Patients (24,652) were included in the study. Of the patients, 93.7% (n = 23,091) were women and 6.3% (n = 1564) were men. Eighteen percent (4636) were dispensed only one prescription. Of the patients, 44.2% included in the study had medication possession ratio (MPR) ≥80% over follow-up period; 8922 (36.2%) who were prescribed from 2001 to 2015 persisted for 1 year with MPR ≥80% and 19.8% persisted for 3 years. Forty percent of expenditure on osteoporosis medication was made for treatment courses with insufficient adherence., Conclusions: There is room for improvement in Estonia with medication adherence relating to all three aspects that determine adherence-initiation, implementation, and persistence. This means further efforts are to be made to educate patients and healthcare professionals on realizing the importance of good adherence.

The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto)immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.

Aim and Methods: We conducted this case study in order to test how health system performance could be compared using the existing national administrative health databases containing individual data. In this comparative analysis we used national data set from three countries, Estonia, Israel and Finland to follow the medical history, treatment outcome and resource use of patients with a chronic disease (diabetes) for 8 years after medical treatment was initiated., Results: This study showed that several clinically important aspects of quality of care as well as health policy issues of cost-effectiveness and efficiency of health systems can be assessed by using the national administrative health data systems, in case those collecting person-level health service data. We developed a structured study protocol and detailed data specifications to generate standardized data sets, in each country, for long-term follow up of incident cohort of diabetic persons as well as shared analyzing programs to produce performance measures from the standardized data sets. This stepwise decentralized approach and use of anonymous person-level data allowed us to mitigate any legal, ownership, confidentiality and privacy concerns and to create internationally comparative data with the extent of detail that is seldom seen before. For example, our preliminary performance comparisons indicate that higher mortality among relatively young diabetes patients in Estonia may be related to considerably higher rates of cardiovascular complications and lower use of statins., Conclusions: Modern administrative person-level health service databases contain sufficiently rich data in details to assess the performance of health systems in the management of chronic diseases. This paper presents and discusses the methodological challenges and the way the problems were solved or avoided to enhance the representativeness and comparability of results., (Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

The aims of the study were to analyze the trends and characteristics of the incidence and clinical presentation of childhood celiac disease (CD) from 1976 to 2010 in Estonia. The study included all children up to 19 years of age diagnosed with small bowel biopsy proven CD. During a 35-year period, CD was diagnosed in 152 children in Estonia (68 boys, median age 2.3 years). From 1976 to 1980, the age-standardized incidence rate of CD was 0.10 per 100,000 person-years. After the introduction of gliadin and endomysium antibody screening (in conjunction with activities directed to increase the physicians awareness), the incidence rate increased from 0.48 in 1986-1990 to 1.55 per 100,000 person-years in 1991-1995. After initiating screening with anti-tissue transglutaminase antibodies in 2003 and routine screening for CD among all children with newly diagnosed type 1 diabetes in 2005, the incidence rate increased from 1.59 in 2001-2005 to 3.14 per 100,000 person-years in 2006-2010 (median age 6.8 years). Our nationwide study demonstrates a more than 30-fold increase in the incidence of childhood CD over a 35-year period in Estonia, along with changing patterns in the presentation of pediatric CD. In addition to the impact of use of novel CD screening methods, active search and rising of the awareness among doctors may have strongest effect. Both environmental and social factors could be also involved in the increase in CD incidence.

Aim: To characterize dynamics of mucosal colonization of neonates by common aerobic Gram negative species and Candida spp. and to identify independent perinatal, neonatal, and environmental factors influencing the colonization process., Study Design: The nasopharyngeal (n=1145) and rectal (n=1242) swabs were collected on admission and thereafter twice a week in neonates with risk factors of early onset sepsis (n=276) admitted within the first 72 h of life. The association between colonization by different microbes and a total of 22 predefined risk factors was assessed using univariate and multiple logistic regression analyses., Results: Throughout the study about half of the patients had rectal (55.8%) or nasopharyngeal colonization (42.8%) with common Gram-negative microorganisms. Colonization dynamics and risk factors were in general similar for a given bacterial species in both mucosal sites; nonfermentative microbes more often found in nasopharyngeal swabs and Enterobacteriaceae in rectal swabs. All organisms except Escherichia coli were influenced by the duration of intensive care unit stay but other risk factors were species specific, perhaps reflecting their mode of acquisition. While colonization by E. coli and Candida albicans was associated with perinatal factors like term birth, vaginal delivery, and breast milk feeding; colonization by Klebsiella pneumoniae, Enteribacter cloacae, Acinetobacter spp. and non-albicans Candida spp. were mostly determined by hospital environment (treatment unit and period, artificial interventions and their duration) and gestation age ≤ 28 weeks., Conclusions: The knowledge of risk factor profiles may permit the development of strategies to prevent heavy colonization and subsequent invasive disease in high risk infants., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We aimed to analyse the availability of paediatric information in Summaries of Product Characteristics (SPC) of ambulatory prescription medicines used in children and to compare the SPC information with other information sources., Methods: In a cross-sectional drug utilisation study based on national prescription database, we analysed all dispensed prescriptions to subjects of <19 years in 2007. We reviewed SPCs of drugs for paediatric information and categorised them as being labelled, off-label and unlicensed., Results: Of 467,334 prescriptions dispensed to 151, 476 children, 69% were for labelled, 31% for off-label and 0.05% for unlicensed drugs. The proportion of prescriptions for drugs being off-label because of missing data was the highest in genitourinary group (97%) and dermatologicals (74%); off-label use because of contraindication in the musculoskeletal group (69%). The highest proportion of off-label drugs was among children aged less than 2 years and the lowest for 2-6-year-olds. Contraindicated medicines were most often prescribed to adolescents. Systemic drugs were more frequently prescribed according to the label than topical agents. SPCs were found often not to be comparable with the other information sources., Conclusions: We show that one-third of Estonian children treated with prescription medicines are exposed to drugs not labelled for paediatric use. We believe that this is not only partly due to the limited number of paediatric trials but also due to lack of up-to-date information in the SPCs. We suggest that paediatric information should be regularly updated in SPCs to ensure that it is based on the best currently available evidence., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: The amount of blood that can be safely drawn from a preterm neonate for scientific purposes is poorly established., Objectives: To provide scientific evidence on the amount of blood that can be drawn from very low birth weight (VLBW) neonates for study purposes., Methods: We performed a post-hoc analysis of a pharmacokinetic (PK) study of penicillin-G, enrolling 18 neonates with a birth weight of <1,200 g, gestational age of <28 weeks and postnatal age of <5 days, with a risk of early onset sepsis. A median of 2.3 ml/kg of blood was collected from each neonate for the PK analysis. Hemoglobin (Hgb), hematocrit (Ht), basic hemodynamic parameters, total fluid intake, number of blood component transfusions and number of blood analysis for clinical indications were recorded. The control group consisted of 35 gestational age-, postnatal age- and birth weight-matched neonates who had not participated in a PK study., Results: We did not observe significant differences in any studied safety parameter, including Hgb and Ht values, between the two groups. Median number of blood component transfusions (n = 2 in both groups), median volume of transfused red blood cells (22 vs. 24 ml/kg in study vs. control group) and total daily fluid requirement were similar. The median calculated blood loss on clinical indications was 1.9 ml/24 h in the control group and 1.66 ml/24 h in the study group., Conclusions: In VLBW neonates, up to 2.3 ml/kg of blood (corresponding to 2.4% of calculated circulating blood volume) can be drawn for scientific purposes without compromising basic hemodynamic parameters, Hgb and Ht values, blood component transfusions or fluid requirements., (Copyright © 2011 S. Karger AG, Basel.)

Introduction: It is well established that severe periodontitis clusters in families, but there are no data about the relationship between mothers with chronic periodontitis and their children's periodontal status., Objective: To evaluate a risk for periodontal diseases in children of periodontally diseased and healthy mothers., Methods: Four study groups were included: (I) 20 female patients with untreated generalized severe chronic periodontitis, (II) their children (34), (III) 13 periodontally healthy mothers and (IV) their children (13). Material was collected from years 2004-2006. The clinical examination included registration of visible plaque index, modified gingival index and, bleeding sites on probing. Periodontal microbiological samples were obtained from all study subjects and the isolates were identified according to morphology and biochemical profiles; similar interfamilial pathogens were compared by PCR-technique., Results: The children of diseased mothers more frequently had periodontal diseases, especially gingivitis. In addition, clinical parameters of gingival inflammation were more expressed and oral hygiene was worse in this group of children. VPI and VPI% of the diseased and healthy mothers differed significantly. The most common oral pathogens were P. intermedia/nigrescens and A. actinomycetemcomitans. The children of healthy mothers harboured pathogens less frequently than the children of diseased mothers. The sharing of P. intermedia/nigrescens was more frequent (5 families) than A. actinomycetemcomitans (2 families)., Conclusion: Maternal indicators, such as periodontitis, hygiene habits, and periodontal microflora are risk factors for childhood periodontal diseases, and might be predictive of future childhood and adolescent periodontitis.

Background: About 10-20% of neonates with suspected or proven early onset sepsis (EOS) fail on the empiric antibiotic regimen of ampicillin or penicillin and gentamicin. We aimed to identify clinical and laboratory markers associated with empiric antibiotic treatment failure in neonates with suspected EOS., Methods: Maternal and early neonatal characteristics predicting failure of empiric antibiotic treatment were identified by univariate logistic regression analysis from a prospective database of 283 neonates admitted to neonatal intensive care unit within 72 hours of life and requiring antibiotic therapy with penicillin or ampicillin and gentamicin. Variables, identified as significant by univariate analysis, were entered into stepwise multiple logistic regression (MLR) analysis and classification and regression tree (CRT) analysis to develop a decision algorithm for clinical application. In order to ensure the earliest possible timing separate analysis for 24 and 72 hours of age was performed., Results: At 24 hours of age neonates with hypoglycaemia < or = 2.55 mmol/L together with CRP values > 1.35 mg/L or those with BW < or = 678 g had more than 30% likelihood of treatment failure. In normoglycaemic neonates with higher BW the best predictors of treatment failure at 24 hours were GA < or = 27 weeks and among those, with higher GA, WBC < or = 8.25 x 10(9) L(-1) together with platelet count < or = 143 x 10(9) L(-1). The algorithm allowed capture of 75% of treatment failure cases with a specificity of 89%. By 72 hours of age minimum platelet count < or = 94.5 x 10(9) L(-1) with need for vasoactive treatment or leukopaenia < or = 3.5 x 10(9) L(-1) or leukocytosis > 39.8 x 10(9) L(-1) or blood glucose < or = 1.65 mmol/L allowed capture of 81% of treatment failure cases with the specificity of 88%. The performance of MLR and CRT models was similar, except for higher specificity of the CRT at 72 h, compared to MLR analysis., Conclusion: There is an identifiable group of neonates with high risk of EOS, likely to fail on conventional antibiotic therapy.

Background: Identification of factors that determine quality of life is important in order to better tailor health and social care services, and thereby improve the functioning and well being of people living with HIV. The estimated number of people living with HIV in eastern Europe and central Asia is 1.6 million. Little is known about the quality of life of people living with HIV in this region. The main purpose of the present study was to identify the factors influencing quality of life in a sample of HIV-infected persons in Estonia., Methods: A convenient sample of 451 patients attending three infectious diseases clinics for routine HIV clinical care visits was recruited for a cross-sectional survey. The World Health Organization's Quality of Life HIV instrument was used to measure quality of life of the participants and medical data was abstracted from clinical records., Results: Good overall quality of life was reported by 42.6% (95% CI: 38.0-47.2%) of the study participants (53% men, 60% self-identify as injecting drug users, 82% <30 years of age, 30% with CD4+ T cell count <300 cells/mm3, and 22% on antiretroviral treatment). We identified the following variables as independent predictors of good overall quality of life: being currently employed or studying (AOR: 2.27, 95% CI: 1.18-4.38); and the absence of HIV-related symptoms (AOR: 2.31, 95% CI: 1.24-4.29)., Conclusion: A comprehensive and competent care system, including health care providers and social workers, is required for an effective response. In addition, social interventions should seek to enhance the economic and employment opportunities for people living with HIV in the region.

Objective: To assess the long-term outcome of bystander-witnessed out-of-hospital cardiac arrest victims in Estonia by using the survival rate and quality of life assay., Methods: All resuscitation attempts made from 01.01.1999 to 31.12.2002 in Estonia were retrospectively screened for bystander-witnessed adult out-of-hospital cardiac arrests of cardiac origin. The patients who survived hospital discharge were included in the study. Their long-term survival data were retrieved from Estonian Population Registry on March 15, 2004. Quality of life was assessed by RAND-36 questionnaire. Comparisons were made with population norms, and patients suffering from myocardial infarction or angina pectoris., Results: 854 bystander-witnessed resuscitation attempts were made in four years. 91 patients (10.7%) survived to hospital discharge. Their one-year survival rate was 77.0% and five-year survival rate 64.3%. 44 patients responded to quality of life questionnaire, sent 16-62 months after out-of-hospital cardiac arrest (response rate 77.2%). Respondents rated their quality of life significantly worse than general population in five out of eight categories. The out-of-hospital cardiac arrest survivors with known cardiovascular disease in history (n=30) had quality of life similar to patients suffering from myocardial infarction or angina pectoris who had not required resuscitation., Conclusion: In Estonia majority of bystander-witnessed out-of-hospital cardiac arrest victims who survive hospital discharge are alive one and also more than three years after resuscitation. Their quality of life is worse than that of general population.

Objective: To investigate treatment adherence and factors related to non-adherence in the Estonian postmenopausal hormone therapy (EPHT) trial., Methods: A total of 1823 postmenopausal women aged 50-64 years were recruited into the EPHT trial from 1999 to 2001. They were randomised into the blind group receiving continuous orally administered postmenopausal hormone therapy (PHT) or a placebo and to a non-blind group receiving open-label PHT or no drugs. A woman was classified as non-adherent, if she had stopped treatment for at least 6-month period in treatment arms or used PHT for at least 6-month period in the control group. Adherence was calculated by the Kaplan-Meier method, and factors affecting adherence were studied with Cox proportional hazard modelling., Results: The rate of adherent women declined approximately 50% during the first year in all treatment arms. Less than 10% of the control group women started taking prescribed PHT. Older women, with lower education, with only one birth, never used oral contraceptives (OC), with lower physical activity or who were dissatisfied with the information received from the trial staff, were more likely to discontinue. In treatment arms, the two most often cited reasons for non-adherence were side-effects and woman's loss of interest in participation. Control group women started PHT due to the menopausal symptoms or on doctor's recommendation., Conclusions: The adherence was similar to that found for PHT use in everyday life. Higher adherence was related to younger age, higher education, previous OC use, physical activity and satisfaction with received information.

Establishing consistency between cerebral palsy registries in reporting of new cases enables more effective collaboration in terms of researching predisposing factors. To identify antenatal and intrapartum risk factors for cerebral palsy in the Estonian population, we undertook a matched case-control study of 153 children with cerebral palsy, ascertained from a population-based survey. One hundred two maternal, antenatal, and intrapartum variables were initially retrieved from medical records. Main outcome measures were the odds ratio estimates of relative risk of cerebral palsy. As a result of the study, and considering the whole spectrum of severity, the relevant risk factors during pregnancy were bleeding after 20 weeks, anemia in the second half of pregnancy, pregnancy-induced hypertension in the second half of pregnancy, and preeclampsia. The most important intrapartum factors were premature birth, placental abruption, an acute hypoxic event during delivery, and any fetal presentation other than vertex. Predisposing factors related to neonatal condition were an Apgar score < or = 7 at the first and fifth minutes of life, hypoxic-ischemic encephalopathy, and assisted ventilation. Our findings suggest that intrapartum factors, including those hypothetically realized through hypoxic-ischemic pathways, are not of low importance in the etiology of cerebral palsy.

The aim of this prospective cohort study was to evaluate the influence of different antenatal factors on neurologic signs in the first days of life and neurodevelopmental outcome at 2 years of age. The study group consisted of 390 children drawn from a cohort of 828 consecutive live births. The data about potential antenatal risk factors, birth complications, and neonatal course were abstracted from pregnancy and delivery records and the hospital register. Odds ratio estimates with 95% confidence intervals were used to measure the associations between antenatal factors and neurologic status in newborns and at 2 years of age. Significance level was set at P < .05. At the mean age of 2 years, 49 of 390 children exhibited adverse neurodevelopmental outcome (cerebral palsy and other developmental disorders). The development of 341 children was normal. Comparative analysis of risk factors was conducted. The strongest correlation with development of hypoxic-ischemic encephalopathy during the first days of life was found in trichomoniasis during pregnancy (odds ratio 4.34; 95% confidence interval 1.32-14.23) and acute respiratory disease (temperature > or = 38 degrees C) in the second half of pregnancy (odds ratio 2.86; 95% confidence interval 1.08-7.58). Of various antenatal factors, bacterial vaginosis combined with impending abortion in the first half of pregnancy (odds ratio 4.96; 95% confidence interval 1.35-18.26) had a significant association with adverse outcome at 2 years of age. The presence of at least one complication at delivery placed the child at risk of adverse neurologic outcome (odds ratio 2.44; 95% confidence interval 1.32-4.54). The study provides supportive evidence that antenatal factors associated with maternal infections can influence the development of hypoxic-ischemic encephalopathy and later neurodevelopmental outcome. These children should be assigned to risk groups for early intervention.