Estonian Patients Research Articles

Genetic susceptibility to temporomandibular joint involvement in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long-term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions. Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ-JIA, a condition not previously studied in this context. The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank. We identified six loci as being associated with the risk of TMJ-JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10-6), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10-6), NLRP3 rs2056795 (P = 8.91 × 10-6) and MAP2K4 rs7225328 (P = 1.64 × 10-5). This study provides first insights into the risk-associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients.

Reduced ovarian cholesterol and steroid biosynthesis along with increased inflammation are associated with high DEHP metabolite levels in human ovarian follicular fluids

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples.Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at “high” (mean 7.7 ± SD 2.3 nM, N = 48) and “low” (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing.Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05).In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP.

The Current State and Usage of European Electronic Cross-border Health Services (eHDSI)

Introduction: European Union intends to enable cross-border health services through a program referred to as “MyHealth@EU”. The first main service is the dispensation of medicine by interlinking national electronic prescription systems. The second one is the Patient Summary, which enables providing the basic set of patients’ medical data. Methods: The contemporary technical documentation of the project was studied and selected published Key Performance Indicators of the project were analyzed. Where necessary, data were acquired directly from the European Commission. Results: Data from the start of the project (fourth quarter of 2019) until the second quarter of 2022 were analyzed. During this time both the overall number of EU countries with operational cross-border healthcare and their particular abilities in both services have risen. At present, there are eleven countries with capabilities in at least one of the services, of which nine have reported transactions. More countries are in the test phase now and will join the operational phase of the project shortly. Discussion and Conclusion: Nevertheless, the program is still used mostly for testing purposes. It seems that only electronic prescription and dispensation are commonly and widely used so far and only Estonian and Finnish patients usually get their medication dispensed abroad. The rest of the operational countries is still at present missing country pairs with a strong cross-border use case.

The prevalence of germline pathogenic variants in Estonian colorectal cancer patients: results from routine clinical setting 2016-2021.

Background: Colorectal cancer (CRC) is the third most common cancer in Estonia in both women and men. According to the Estonian National Institute for Health Development, in 2017, there were 357 new colon cancer only cases in women and 282 in men. For colorectal cancer, the number for men and women altogether was 1040 in the same year. In 2018, there were over 1.8 million new cases worldwide. The Mayo Clinic found in a prospective, two-year multi-site study of CRC patients that 15.5% of patients carried pathogenic germline variants (PGV), using an >80 gene Next Generation Sequencing (NGS) panel. Material and methods: This retrospective study aimed to analyse the estimated prevalence of pathogenic/likely pathogenic germline variants in Estonian colorectal cancer patients using NGS in a routine clinical setting. We gathered five-year data (July 2016-July 2021) of colorectal cancer patients (mostly not selected for age or family history) tested with either Illumina TruSight Cancer (94 genes) or TruSight Hereditary Cancer (113 genes) NGS panels. Results: Three hundred and fourteen NGS analyses were performed due to either CRC or polyposis in anamnesis and/or family anamnesis, including 126 CRC cases and 44 colorectal polyposis cases, while 144 were either healthy family members or had other types of cancers. While a known disease-causing variant was identified in 16.4% of all cancer patients tested, we found that 21.4% of CRC patients had such a variant. Among the 44 colorectal polyps cases MLH1, gene was the most affected one (25%), the second and third most affected genes were MSH2 and CHEK2. Other genes with disease-causing variants found in CRC patients included APC, BLM, BMPR1A, BRCA1, FANCM, MSH6, MUTYH, PMS2, SMAD4, SPINK1 and VHL. Conclusion: Our result give an overview of genetic testing of CRC patients, the prevalence of disease-causing variants and their landscape in Estonia. According to Estonian data, only 2.7-6.1% of CRC patients are genetically tested, which is around ten times less frequently than breast cancer patients and their family members. The diagnostic yield of CRC patients is 21.4%, suggesting that genetic testing will likely improve timely diagnosis and outcomes.

Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

BackgroundJuvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients.MethodsWe performed genome-wide association analyses in an entire JIA case–control sample (All-JIA) and in a case–control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls.ResultsWe demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10−6), LTBP1 (P = 9,45 × 10−6), and ELMO1 (P = 1,05 × 10−5). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10−6), LTBP1 (P = 9,95 × 10−6), MX1 (P = 1,65 × 10−5), and CD200R1 (P = 2,59 × 10−5).ConclusionThis study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients.Key Points• Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition.• Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe.• The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci.• The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.

Changes in the quality of care of colorectal cancer in Estonia: a population-based high-resolution study

ObjectivesLarge disparities in colorectal cancer (CRC) management and survival have been observed across Europe. Despite recent increases, the survival deficit of Estonian patients with CRC persists, particularly for rectal cancer....

Community-based genetic study of Parkinson's disease in Estonia.

To examine the genetic variability of Estonian Parkinson's disease (PD) patients using an ongoing epidemiological study in combination with a genetic analysis. This study was a community-based genetic screening study of 189 PD patients, and 158 age- and sex-matched controls screened for potential mutations in 9 PD genes using next-generation sequencing and multiplex ligation-dependent probe amplification method. Different clinimetric scales and questionnaires were used to examine PD patients and assess clinical characteristics and severity of the disease. The overall frequency of pathogenic PD-causing variants was 1.1% (2/189), and any rare genetic variant was present in 21.2% (40/189) of the patients and in 8.2% (13/158) of the controls (P<.05). Variants of unknown significance accounted for 10.6% (20/189). Frequency of any GBA variant among PD patients was 10.1% (19/189) and in controls 3.8% (6/158). The frequency of any GBA variant in PD compared to controls was significantly higher (P=.035; OR 2.82; CI 95% 1.05-8.87). Burden of rare variants was not different between patients and controls. Also, a novel GBA pathogenic variant p.E10X was detected. Among different genetic variants identified in Estonian PD patients, GBA variants are the most common, while an overall pathogenic variant frequency was 1.1%.

A retrospective analysis of the prevalence of imprinting disorders in Estonia from 1998 to 2016.

Imprinting disorders (ImpDis) represent a small group of rare congenital diseases primarily affecting growth, development, and the hormonal and metabolic systems. The aim of present study was to identify the prevalence of the ImpDis in Estonia, to describe trends in the live birth prevalence of these disorders between 1998 and 2016, and to compare the results with previously published data. We retrospectively reviewed the records of all Estonian patients since 1998 with both molecularly and clinically diagnosed ImpDis. A prospective study was also conducted, in which all patients with clinical suspicion for an ImpDis were molecularly analyzed. Eighty-seven individuals with ImpDis were identified. Twenty-seven (31%) of them had Prader-Willi syndrome (PWS), 15 (17%) had Angelman syndrome (AS), 15 (17%) had Silver-Russell syndrome (SRS), 12 (14%) had Beckwith-Wiedemann syndrome (BWS), 10 (11%) had pseudo- or pseudopseudohypoparathyroidism, four had central precocious puberty, two had Temple syndrome, one had transient neonatal diabetes mellitus, and one had myoclonus-dystonia syndrome. One third of SRS and BWS cases fulfilled the diagnostic criteria for these disorders, but tested negative for genetic abnormalities. Seventy-six individuals were alive as of January 1, 2018, indicating the total prevalence of ImpDis in Estonia is 5.8/100,000 (95% CI 4.6/100,000-7.2/100,000). The minimum live birth prevalence of all ImpDis in Estonia in 2004-2016 was 1/3,462, PWS 1/13,599, AS 1/27,198, BWS 1/21,154, SRS 1/15,866, and PHP/PPHP 1/27,198. Our results are only partially consistent with previously published data. The worldwide prevalence of SRS and GNAS-gene-related ImpDis is likely underestimated and may be at least three times higher than expected.

Stable level of HIV transmitted drug resistance in Estonia despite significant scale-up of antiretroviral therapy

BackgroundDue to the widespread use of non-nucleoside reverse transcriptase inhibitors (NNRTI) as part of first-line therapies to curb the human immunodeficiency virus (HIV) epidemic in Eastern-European countries, transmitted drug resistance (TDR) is of serious concern in this region. Therefore, TDR and its associated risk factors were investigated among newly diagnosed HIV-1 subjects in Estonia. MethodsThis nationwide observational study included all newly diagnosed HIV-1 subjects from January 1 until December 31, 2013. Demographic and clinical data were collected using the national surveillance system and the Estonian HIV-positive patient database (E-HIV). Starting from RNA, the HIV-1 protease (PR) and reverse transcriptase (RT) region was sequenced and surveillance drug resistance mutations (SDRM) were determined. Sequences from previous studies in Estonia and from public databases were included to study epidemic trends and to determine TDR clusters by phylogenetic analysis. ResultsOut of 325 newly diagnosed HIV-1 infections, 224 were successfully sequenced (68%). As in previous studies from Estonia, the circulating recombinant form CRF06_cpx was the most prevalent HIV subtype (164/224, 74%). Fifteen strains displayed SDRM, giving a TDR rate of 6.7% (95% CI 3.9; 11.0). The most common SDRMs were associated with NNRTI (10/15, 4.5%), followed by PI (3/15, 1.3%) and NRTI (2/15, 0.9%). K103 N (8/15, 53%) was the most common SDRM. The level of TDR and mutational patterns were comparable to previous years. Twenty-six transmission clusters containing Estonian sequences were observed, of which 23/26 belonged to CRF06_cpx and 2/26 displayed evidence of TDR. The only risk factor associated with the presence of TDR was imprisonment (OR 5.187, CI 1.139–25.565, p = 0.034). ConclusionsTDR remained stable at a moderate level in Estonia, K103N is the main SDRM with only one transmission-pair detected. We suggest screening for TDR at the time of diagnosis or prior to antiretroviral treatment initiation to tailor first-line regimens accordingly. SummaryThe third consecutive transmitted drug resistance (TDR) study demonstrated a stable TDR in Estonia. TDR reached 6.7% (moderate level) in 2013, with imprisonment being the only associated risk factor. Few drug resistance-associated transmission clusters were identified.

The evaluation of phenylalanine levels in Estonian phenylketonuria patients during eight years by electronic laboratory records

Blood phenylalanine (Phe) values from the dried blood spots of all Estonian phenylketonuria (PKU) patients have been deposited into a unified electronic laboratory database for eight years, providing an opportunity to assess the adherence of the patients to dietary recommendations over time and to observe patient practices both individually and collectively. Our results demonstrate generally good adherence to clinical and dietary recommendations during the first six years of life, as the percentage of patients with median Phe values fitting under the national recommendation levels were 95%, 84% and 70% in age groups 0–1, 1–2 and 2–6 years, respectively. Conversely, significant deviations occur in the group of 6 to 12 year-olds, mildly decreasing in adolescence and increasing in adulthood (43%, 53% and 57%, respectively). Wide individual differences occurred in all groups, especially in patients with a classical PKU phenotype caused by PAH variants that fully abolish phenylalanine hydroxylase activity. Surprisingly, some of the best dietary adherence was seen in the late-diagnosed PKU patients with poor cognitive functioning. As a rule, the median of Phe values crosses the recommended thresholds in approximately one third to one half of the patients of each age group after the first two years of life.

Adaption and validation of the Mississippi Aphasia Screening Test to Estonian speakers with aphasia.

ObjectivesThe Mississippi Aphasia Screening Test (MAST) is a brief screening tool for assessing the expressive and receptive language abilities of patients with aphasia. The goal of this study was to adapt and validate the MAST into the Estonian language. The discriminant validity and internal consistency of the test were examined, as well as its sensitivity and specificity.MethodsThe MASTest was administered in 50 left hemisphere stroke patients with aphasia (LHA+ group) in the acute phase after the stroke and 126 healthy volunteers in a control group (CG), stratified by age and level of education. Nonparametric tests were used to get normative values, compare the values of the MASTest scores between the LHA+ group and the CG, and to assess the discriminant validity, internal consistency, sensitivity, and specificity of the MASTest.ResultsThe summary scores: total score (MASTest‐T), expressive score (MASTest‐E), and receptive score (MASTest‐R) correlated with age and educational level, and the normative values were adjusted accordingly. The LHA+ group showed more impairment than the CG in all subtests and summary scores. The internal reliability of the MASTest was high for the whole sample and LHA+ group. The sensitivity and specificity of the MASTest using the 5th percentile were 74% and 94%, respectively, but using receiver operating characteristic (ROC) analysis, it was 89% and 80%.ConclusionThe MASTest is a valid screening tool for evaluating expressive and receptive language abilities in Estonian patients with aphasia in early stroke. The MASTest is the first validated aphasia screening test for Estonian‐speaking people, who number less than one million worldwide.

Antimicrobial resistance and multilocus sequence types of Campylobacter jejuni isolated from Baltic broiler chicken meat and Estonian human patients.

Genotypes of Campylobacter jejuni in Baltic fresh broiler chicken meat and in Estonian human origin samples were determined by using MLST. We observed associations between clonal complexes, sequence types, and antibiotic resistance of C. jejuni isolates. The detection of high proportions of fluoroquinolone resistance among Latvian (100.0%) and Lithuanian (84.6%) origin broiler chicken meat C. jejuni isolates, found in this study, suggests the wide use of these antibiotics in poultry in these countries. MLST of 48 Baltic origin C. jejuni isolates revealed a total of 22 sequence types belonging to 13 clonal complexes. From the 13 assigned CCs and 22 STs, the most prevalent were ST-353 CC and ST-5 consisting of human, Latvian and Lithuanian chicken meat isolates. Among human and chicken meat isolates the resistance rate was 63.6 and 62.2%, respectively. ST-353 isolated from humans were more often resistant to nalidixic acid and ciprofloxacin than the other STs. Strain types ST-5, ST-50, ST-353, ST-354, and ST-429 isolated from poultry were more often resistant to both nalidixic acid and ciprofloxacin than the other STs. Furthermore, ST-353 and ST-354 isolated from poultry were more often resistant against tetracycline than the other STs. Fluoroquinolone resistance was significantly (P < 0.01) associated with ST-353 CC and ST-5 in comparison with all other CCs, STs. We found that three Estonian broiler isolates belonged to the novel ST-8188.The study indicates the potential public health concern posed by the very high fluoroquinolne resistance in Campylobacter jejuni found in Latvian and Lithuanian poultry meat.

Nasolabial aesthetics of patients with repaired unilateral cleft lip and palate: A comparison of three rating methods in two countries

ObjectivesThe study aimed to compare nasolabial aesthetics of patients with unilateral cleft lip and palate (UCLP) treated in Vietnam and Estonia using three rating methods: five-point aesthetic index, a visual analogue scale (VAS), and reference scores method. MethodsA total of 56 patients with repaired UCLP (23 from Vietnam and 33 from Estonia) were included in this cross-sectional study. Patients' facial and profile photographs were cropped to reveal the nasolabial region and coded. Five examiners rated nasolabial aesthetics of the patients using three methods: five-point aesthetic index, 100 mm VAS, and reference scores method. Intraclass correlation coefficients were used to evaluate intrarater and interrater reliabilities. ResultsThe five-point aesthetic index had a higher reliability than VAS and reference scores method. The least aesthetic feature among Vietnamese and Estonian patients was nasal symmetry and nasolabial profile respectively. No differences in nasolabial aesthetics were found between Vietnamese and Estonian patients regardless of the rating methods (p > 0.05) except for nasal symmetry. ConclusionsThe five-point aesthetic index seems to produce more reproducible results. There were no significant differences in nasolabial aesthetics between the two countries. Overall average nasolabial appearance results were obtained using different treatment protocols in the two countries.

Hepatitis E virus infection in different groups of Estonian patients and people who inject drugs

BackgroundPreviously we demonstrated a high prevalence of hepatitis E virus (HEV) in domestic pigs and wild boars, the main reservoir and possible source of HEV infections in humans. But so far there are no reports about spread of HEV in Estonian human population. ObjectivesThe present study aimed to determine the prevalence and genotyping of HEV in different groups of the Estonian adult population. Study designTotally 1426 human serum samples were tested (763 patients with clinically diagnosed nonA/B/C hepatitis, 176 hemodialysis patients, 282 patients with suspected HEV infection and 205 people who injected drugs (PWID)). Presence of anti-HEVantibodies was assessed by ELISA and confirmed by immunoblotting. All anti-HEV positive sera were analyzed for RNA by qPCR. Amplified ORF2 region was sequenced and used for phylogenetic analysis. ResultsAntibody assay revealed 49 samples from 1426 (3.4%) with acute (17) or past (32) HEV infection. HEV RNA was detected in 10 anti-HEV IgM positive samples, including 9 samples from patients with suspected HEV infection and 1 hemodialysis patient. Anti-HEV IgG were found in 7.8% patients with suspected HEV infection, in 4% hemodialysis patients, in 2.4% PWID and in 1.96% patients with nonA/B/C hepatitis. All groups demonstrated a trend to share of anti-HEV seroprevalence increasing with age. Phylogenetic analysis of 9 HEV RNA sequences revealed that 3 sequences belonged to HEV genotype 1; 6 ones to genotype 3 (1 sequence belonged to sub-genotype 3a, two ones – sub-genotype 3e, and three ones – to sub-genotype 3f). ConclusionsDespite the high seroprevalence among domestic pigs, no evidence of HEV transmission from Estonian pigs to humans was found. The results of our study suggest that HEV infections in Estonia are most likely associated with travel or with consumption of imported food products.

The Prevalence of Helicobacter pylori in Estonian Bariatric Surgery Patients.

Helicobacter pylori (Hp) is one of the most important human pathogens that can cause duodenal and gastric ulcers, gastritis and stomach cancer. Hp infection is considered to be a cause of limiting access to bariatric surgery. The aim of this study was to determine the prevalence of Hp in patients with obesity going into bariatric surgery and to reveal the relationship between Hp and clinical data. The study group was formed of 68 preoperative bariatric surgery patients (body mass index (BMI) 44.7 ± 4.8). Gastric biopsies (antrum and corpus) were used for histological and molecular (caqA and glmM genes) examinations. The PCR method revealed Hp infection in 64.7% of obese patients that is higher in comparison with histological analysis (55.9%). The prevalence of cagA and glmM genes in antrum mucosa was 45.6% and 47.0% while in the corpus it was 41.2% and 38.3%, respectively. The coincidence of both cagA and glmM virulence genes in the antrum and corpus mucosa was 33.8% and 22.1%, respectively. Either of the genes was found in 58.8% of antrum and 57.3% of corpus mucosa. Presence of caqA and glmM genes was in association with active and atrophic chronic gastritis. In conclusion, our study demonstrated that two thirds of morbidly obese patients undergoing bariatric surgery are infected with Hp and have a high prevalence of cagA and glmM virulence genes that points out the necessity for diagnostics and treatment of this infection before surgery.

Prevalence of depressive symptoms and their association with brainstem raphe echogenicity in patients with Parkinson's disease and non-PD controls

Despite advances in diagnostics and clinical recognition, depressive symptoms in Parkinson's disease (PD) exceeding normal limits remain effectively untreated. In this study, we report on the prevalence and severity of depressive symptoms as well as their association with brainstem raphe echogenicity in patients with PD and non-PD controls. The study included 266 Estonian PD patients and 168 age- and education-matched controls. Demographic and clinical data was documented. Brainstem raphe (BR) was visualized by transcranial sonography (TCS). The prevalence of depressive symptoms in the patient sample was found to be significantly higher than in controls. BR echogenicity in both patients and controls was directly related to their total BDI score, although we found a significantly greater reduction of BR echogenicity in patients with PD and depressive symptoms compared to depressed non-PD controls. The present results corroborate the hypothesis that morphological alteration of the BR is involved in the pathogenesis of depressive disorders. TCS of BR could be used as a non-invasive biomarker to improve detection of depressive symptoms in early PD stages where clinicians may not recognize affective disturbances in the context of PD phenomena.

Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients

BackgroundOsteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country.MethodsWe performed mutational analysis of peripheral blood gDNA of 30 unrelated Estonian OI patients using Sanger sequencing of COL1A1 and COL1A2 genes, including all intron-exon junctions and 5′UTR and 3′UTR regions, to identify causative OI mutations.ResultsWe identified COL1A1/2 mutations in 86.67% of patients (26/30). 76.92% of discovered mutations were located in the COL1A1 (n = 20) and 23.08% in the COL1A2 (n = 6) gene. Half of the COL1A1/2 mutations appeared to be novel. The percentage of quantitative COL1A1/2 mutations was 69.23%. Glycine substitution with serine was the most prevalent among missense mutations. All qualitative mutations were situated in the chain domain of pro-α1/2 chains.ConclusionOur study shows that among the Estonian OI population, the range of collagen I mutations is quite high, which agrees with other described OI cohorts of Northern Europe. The Estonian OI cohort differs due to the high number of quantitative variants and simple missense variants, which are mostly Gly to Ser substitutions and do not extend the chain domain of COL1A1/2 products.

HIV incidence in the Estonian population in 2013 determined using the HIV-1 limiting antigen avidity assay.

Estonia has one the highest number of new HIV diagnoses in the European Union, mainly among injecting drug users and heterosexuals. Little is known of HIV incidence, which is crucial for limiting the epidemic. Using a recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV incidence in 2013. All individuals aged ≥18years newly-diagnosed with HIV in Estonia January- December 2013, except blood donors and those undergoing antenatal screening, were included. Demographic and clinical data were obtained from the Estonian Health Board and the Estonian HIV-positive patient database. Serum samples were tested for recent infection using the LAg-avidity EIA assay. HIV incidence was estimated based on previously published methods. Of 69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age of 33years (IQR: 28-42) and 65% male. Self-reported routes of HIV transmission were mostly heterosexual contact (n=157, 53%) and injecting drug use (n=62, 21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new infections in 2013 among the non-screened population. Incidence was highest (1.48%) among people who inject drugs. These high HIV incidence estimates in Estonia call for urgent action of renewed targeted public health promotion and HIV testing campaigns.

Adherence to osteoporosis medicines in Estonia-a comprehensive 15-year retrospective prescriptions database study.

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. 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 1year. 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 1year with MPR ≥80% and 19.8% persisted for 3years. Forty percent of expenditure on osteoporosis medication was made for treatment courses with insufficient adherence. 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.

Risk Factors and Etiology of Young Ischemic Stroke Patients in Estonia.

Objectives Reports on young patients with ischemic stroke from Eastern Europe have been scarce. This study aimed to assess risk factors and etiology of first-ever and recurrent stroke among young Estonian patients. Methods We performed a retrospective study of consecutive ischemic stroke patients aged 18–54 years who were treated in our two hospitals from 2003 to 2012. Results We identified 741 patients with first-ever stroke and 96 patients with recurrent stroke. Among first-time patients, men predominated in all age groups. The prevalence of well-documented risk factors in first-time stroke patients was 83% and in the recurrent group 91%. The most frequent risk factors were hypertension (53%), dyslipidemia (46%), and smoking (35%). Recurrent stroke patients had fewer less well-documented risk factors compared to first-time stroke patients (19.8 versus 30.0%, P = 0.036). Atrial fibrillation was the most common cause of cardioembolic strokes (48%) and large-artery atherosclerosis (LAA) was the cause in 8% among those aged <35 years. Compared to first-time strokes, recurrent ones were more frequently caused by LAA (14.3 versus 24.0%, P = 0.01) and less often by other definite etiology (8.5 versus 1.0%, P = 0.01). Conclusions The prevalence of vascular risk factors among Estonian young stroke patients is high. Premature atherosclerosis is a cause in a substantial part of very young stroke patients.