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  • Ning, Feng (Helsingin yliopisto, 2013)
    The objectives of this study were to investigate: 1) what the major risk factors are that have contributed to the rise in prevalence of type 2 diabetes in Chinese adults, and whether the joint effect of a family history of diabetes along with obesity on the risk of diabetes in the Chinese differs from that in the Finns; 2) the impact of the homeostasis model assessment of insulin resistance and beta cell function on glucose metabolism in relation to aging in people of Asian origin; 3) the relative risk for cardiovascular disease (CVD) mortality and morbidity associated with fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) within the normoglycemic range in European populations. This study was based on datasets of the Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Asia (DECODA) and in Europe (DECODE) studies comprising 10307 men and 13429 women aged 30 to 74 years from 11 Asian cohorts, and 12566 men and 10874 women aged 25 to 90 years from 19 European cohorts. Type 2 diabetes and intermediate hyperglycemia in this study were determined by a 2-h 75g oral glucose tolerance test according to the World Health Organization/International Diabetes Federation criteria of 2006. The odds ratios for the prevalence of type 2 diabetes and intermediate hyperglycemia were estimated using logistic regression analysis. Cox proportional hazards analysis was performed to estimate the association between plasma glucose and CVD mortality and morbidity, adjusting for conventional cardiovascular risk factors. Between 2001 and 2006, the age-standardized prevalence of type 2 diabetes increased from 5.2% to 14.2% in men and from 7.2% to 14.5% in women in rural areas, from 12.6% to 19.4% in men and from 10.2% to 16.6% in women in urban areas in Qingdao, China. Age, family history of diabetes and waist circumference was independent risk factors for diabetes in both sexes and in both urban and rural areas (P less than 0.01 for all). A high level of education and a high income were inversely associated with the increased prevalence in all populations except in rural men (P less than 0.05). Obesity and a family history of diabetes were major risk factors for type 2 diabetes in men and women from China and Finland. Their synergetic effect on type 2 diabetes was significant in Finnish men, but not in Finnish women or the Chinese. The prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) increased with age in populations of Asian origin except IFG in the Indians living in India and in African men living in Mauritius. The age-related increase was more prominent for IGT than for IFG in both men and women. Adjustment for insulin resistance and beta cell function reduced the differences among age groups for all ethnic groups, but the risk gradient between age groups still remained significant for IGT. Within normoglycemic range, individuals whose baseline 2hPG did not return to FPG levels (Group II, 2hPG > FPG) were older and had higher baseline body mass index (BMI), blood pressure and fasting insulin levels compared with those whose baseline 2hPG did (Group I, 2hPG ≤ FPG) in Europeans. Hazard ratios (95% confidence intervals) for CVD mortality were 1.22 (1.05-1.41) in men, and 1.40 (1.03-1.89) in women for Group II versus Group I, adjusting for age, study cohort, BMI, FPG, total serum cholesterol, smoking status and hypertension status. The corresponding hazard ratios for the incidence of coronary heart disease, ischemic stroke and composite CVD events were 1.13 (0.93-1.37), 1.40 (1.06-1.85) and 1.20 (1.01-1.42) in men, and 1.33 (0.83-2.13), 0.94 (0.59-1.51) and 1.11 (0.79-1.54) in women, respectively. The increasing trends for CVD mortality and morbidity did not change substantially after additional adjustment for fasting insulin concentrations. In conclusion, this study confirmed the impact of established risk factors of age, obesity and a family history of diabetes on the risk of diabetes among the Chinese, which is consistent with literature, but the interaction between the risk factors might be different between ethnicities and requires further investigation. This study also disclosed the deleterious effect of high normal 2hPG levels on CVD mortality and morbidity, which has not been widely investigated previously. The findings further support the view that the CVD risk extends well below the diabetes diagnostic value based on the post-challenge glucose levels, and may have certain clinical implications regarding diabetes diagnosis and glycemic management targets.
  • Lumme, Sonja (2003)
    Tutkielman tarkoituksena on tutustua tilastollisiin menetelmiin, joita käytetään arvioidessa riskiä sairastua syöpään. Tapaus-verrokkitutkimusasetelma on yksi epidemiologiassa eniten käytetyistä menetelmistä, joita käytetään riskin arvioimisessa. Tapaus-kohorttitutkimusasetelma on yksi tapaus-verrokkitutkimusasetelman versio. Työssä on tarkasteltu asetelmia tutkimuksen suunnittelun, aineistojen keräämisen ja analysoimisen näkökulmista. Tutkielma liittyy Suomen Syöpärekisterin ja NBSBCCC:n (Nordic Biological Specimen Banks working group on Cancer Causes and Control) yhteisiin projekteihin, joissa arvioidaan syöpäriskiä veripankkiaineistoja hyödyntäen. Näissä projekteissa on herännyt kysymys, voidaanko toisia tutkimuksia varten aiemmin kerätyistä tapaus-verrokkiaineistoista tehdä vertailukohortti tapaus-kohorttitutkimukselle ja millä edellytyksin se voitaisiin tehdä? Kysymys on tärkeä, sillä jos aiemmin kerätyt aineistot muodostavat luotettavan vertailukohortin, voidaan biologisia näytteitä käyttävissä hankkeissa säästää kustannuksissa. Menetelmiä sovellettiin kahteen biologiseen aineistoon. Nämä aineistot liittyvät NBSBCCC:n tutkimuksiin, joissa on tutkittu papilloomaviruksen ja eri syöpien välistä yhteyttä. Tämän työn toisessa aineistossa on tutkittu pään ja kaulan alueen syöpiä ja toisessa peräaukon ja sitä ympäröivän ihon syöpiä. Papilloomavirusta kantavilla yksilöillä havaittiin olevan tilastollisesti merkitsevästi suurempi riski sairastua kyseisiin syöpiin. Tulokset olivat samansuuntaisia riippumatta analysointimenetelmästä. Tutkielmassa on pohdittu ehtoja, jotka mahdollistavat tapaus-verrokkiaineistojen käyttämisen uudelleen tapaus-kohorttitutkimuksessa. Nämä ehdot koskevat sekä aineistojen keräämistä että aineistojen analysoimista. Tuloksena on, että aiemmin kerätyt tapaus-verrokkiaineistot voivat muodostaa tapaus-kohorttiaineistolle vertailuryhmän, jos vaadittavat ehdot otetaan huomioon tutkimuksessa. Tärkeimmät lähteet: Barlow, W. E. (1994): Robust Variance Estimation for the Case-Cohort Designs. Biometrics 50(4): 1064-72. Barlow, W. E. – Ichikawa, L. – Rosner, D. – Izumi, S. (1999): Analysis of Case-Cohort Designs. Journal of Clinical Epidemiology 52(12): 1165-72. Gail, M. H. – Benichou, J. (toim.) (2000): Encyclopedia of epidemiologic methods. John Wiley & Sons, New York. Prentice, R. L. (1986): A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73(1): 1-11.
  • Kolehmainen, Pekka (Helsingin yliopisto, 2014)
    Human parechovirus (HPeV) and Ljungan virus (LV) are non-enveloped, single-stranded RNA viruses that form the genus Parechovirus in the family Picornaviridae. The interest in these viruses has notably increased over the past 15 years because of their strengthened associations to human and animal diseases. HPeV types 1 and 3 have been associated with more severe infections in young children, such as infections of the central nervous system (CNS) and sepsis-like disease. Rodent-infecting LV has been suggested to possess zoonotic potential and induce various human diseases. However, the proof for this remains lacking. This study aimed to describe the epidemiological features of HPeVs in Finland and in the Netherlands, to examine the connection between HPeV-induced infection and human diseases and to study the circulation of LV in Finland. The epidemiological analysis of stool samples, collected from 1996 to 2007, revealed that HPeVs are highly common in healthy Finnish children. HPeV was primarily detectable in children under 2 years of age. Altogether, 39% of the study participants tested positive for HPeV at least once during the study period. HPeVs circulated throughout the year, with a distinct seasonal peak in October-November. The results indicated that not only the previously described HPeV1 but also HPeV genotypes 3 and 6 circulate in Finland. Microneutralisation assays, which were set up to detect HPeV1 to 6, the most common genotypes in Europe, provided a deeper understanding of HPeV seroprevalence in the Finnish and Dutch populations. Seropositivity for HPeV1, 2 and HPeV4 to 6 was high and moderate in adults, in contrast to seropositivity for HPeV3, which was extremely low. The serological data demonstrate that HPeV types 1 to 6 might be even more prevalent than previously assumed. All six HPeV types circulate in Finland. In addition to HPeV detection in background populations, we presented the first cases of severe infection in neonates with HPeV4 and, subsequently, the first isolation of this genotype in Finland. Five hospitalised neonates with a sepsis-like disease in the fall of 2012 were positive for HPeV. Four of these children had HPeV4, indicating a potential small epidemic of this genotype, whereas one HPeV remained untyped. In addition, we detected HPeV3 in a neonate with suspected viral sepsis in October 2011 and another untyped HPeV in a child with symptoms corresponding to acute disseminated encephalomyelitis in May 2012. Following these findings, we promoted the addition of HPeV detection to routine diagnostics of young children. To extend the knowledge regarding other parechoviruses in Finland, we studied LV antibody prevalence in both humans and rodents. The seroprevalence detected for LV was 38% in humans and 18% in bank voles (Myodes glareolus). The observation of LV antibodies in humans is relatively high because LV has never been isolated from humans. These results suggest that an LV or LV-like virus, in addition to HPeVs, circulates frequently among human populations in Finland.
  • Kirchner, Sascha (Helsingin yliopisto, 2014)
    Background: The control of Potato virus Y (PVY, genus Potyvirus, family Potyviridae) is one of the greatest challenges in seed potato production worldwide. PVY can cause substantial economic losses. It reduces the growth of potato plants and the quality and quantity of yield. Therefore, when virus incidence exceeds set thresholds, the potatoes cannot be sold as seed but have to be sold at a lower price for consumption. PVY is transmitted in a non-persistent manner by winged forms of many aphid species. This mode of transmission is characterised by short probing activity, which is sufficient for acquisition and transmission of the virus. Because of these underlying epidemiological factors, PVY is difficult to control. Around 2005, the High grade (HG) seed potato production area in Finland, which is one of the northernmost intensive crop production areas of the world, saw a marked increase in the incidence of PVY in potato seed lots. Therefore, it became necessary to investigate the epidemiology of PVY and establish measures of PVY control in this region. ----- Aims: 1) To characterise the species composition and phenology of the aphid fauna. 2) To determine the incidence of aphid species with documented ability to transmit PVY and to use a modelling approach to determine their relative importance as vectors including timing of virus transmission. 3) To compare the application of straw mulch, mineral oil and birch extract with chemical practices for control of PVY vectors. Methods: The area under study was Tyrnävä-Liminka (latitude 64°) in Finland. Studies were carried out in the potato growing seasons from 2007 to 2012. Aphid flight activity was monitored by yellow pan traps (YPT) placed in 4 8 seed potato fields per year and by one suction trap. Aphid identification was done by morphological characteristics and by DNA barcoding based on a 658-bp long region of the mitochondrial gene for cytochrome c oxidase I (COI). A cluster analysis was used to categorise phenology of species. Incidence of PVY was measured by testing leaves collected two weeks after plant emergence and in the progeny tubers after harvest by enzyme-linked immunosorbent assay (ELISA). To determine the most important time of transmission of PVY, and the main vectors, the seasonal increase in PVY incidence was modelled using aphid counts in traps, the relative vector efficiencies of the aphids, virus resistance of cultivars, and the initial infection rate of the seed tubers as explanatory variables in generalised linear mixed modelling. In addition, small scale experiments (SSE) were conducted in three years and large scale (LSE) field trials in two years. SSE were set up to compare applications of straw mulch, mineral oil and birch extract with chemical control of PVY vectors. LSE were conducted in growers fields to test efficacy of straw mulch to control PVY at farm scale. ---- Results: A total of 58,528 winged aphid individuals were classified into 83 taxa based on morphology: Of these, 34 species were further characterised by DNA barcoding. Four phenology clusters were found. The late-peak cluster was dominated by heteroecious species and the mid-peak cluster was dominated by monoecious species feeding on herbaceous plants. Total abundance showed a recurring triennial cycle according to the catch of aphids using the suction trap in the years 2000-2010. The most abundant species was Rhopalosiphum padi. It occurred mainly at the end of the potato growing season. The highly polyphagous species, Aphis fabae and Aphis gossypii were found to peak at the beginning of the potato growing season. Results of the modelling approach showed that the incidence of seedborne PVY infection and the early-season flight of Aphis fabae are the most important factors contributing to the incidence of PVY in the yield. Other aphid species play a negligible role as vectors of PVY. In the SSEs, only straw mulch reduced of PVY incidence significantly in the progeny tubers, with the reduction ranging from 50% to 70% in all three years. Incidence of PVY was reduced by mineral oil in two years (by 43% to 58%) and by the synthetic pyrethroid insecticide esfenvalerate by 29% in one year. In the LSE, straw mulch significantly reduced PVY in the progeny tubers by 25% to 47%. Average tuber yield following the straw mulch treatment was generally but not significantly higher than that in the untreated control in all experiments. ---- Conclusion: The results demonstrate that early season flight activity of Aphis fabae determines PVY incidence in the HG seed potato production area of Finland with a generally low vector pressure. Furthermore, straw mulch emerges as a reliabe and effective measure in diminishing the spread of PVY in areas with early vector flight activity.
  • Markkula, Annukka (Helsingin yliopisto, 2013)
    Listeria monocytogenes causes potentially fatal illness to susceptible people and is found in various foods. It typically enters processed foods via a contaminated processing environment, in which it may have persisted for years. To study the role of raw material as a potential source of contamination of food processing plants by L. monocytogenes, the prevalence and genetic diversity of this species in tonsils of pigs and in raw fish was examined. A total of 14% and 4% of tonsils of pigs and raw fish, respectively, harboured L. monocytogenes. From 38 pig tonsil isolates and 11 raw fish isolates, 24 and nine different types were recovered using pulsed-field-gel electrophoresis (PFGE) typing. The results indicate that a wide variety of L. monocytogenes strains enters pork slaughterhouses and fish processing plants in the raw materials, which are thus potential sources of direct or indirect contamination of processing plants by this pathogen. Since identical PFGE types were recovered from both raw and processed fish, it is likely that raw fish are an initial source of the L. monocytogenes found in processed fish. Some strains entering a plant along with raw fish may contaminate and persist in the processing environment, causing recurrent contamination of the final products via contact surfaces. Alternatively, L. monocytogenes strains in raw fish may survive non-listericidal processes, resulting in contamination of the final product. To identify novel factors contributing to survival of L. monocytogenes in food processing environment, the roles of specific genes in stress response were investigated, using flhA and motA that encode flagellar factors involved in cold stress tolerance, and lmo0866, lmo1246, lmo1450, and lmo1722 encoding DEAD-box RNA helicases involved in cold, heat acid, alkali, osmotic, ethanol, and oxidative stress tolerance. Increased relative transcription levels of flhA, motA, lmo0866, lmo1450, and lmo1722, restricted growth of the single gene deletion mutant strains EGD-eΔflhA, EGD-eΔmotA, Δlmo0866, Δlmo1450, and Δlmo1722 at 3°C, and increased minimum growth temperatures of Δlmo0866, Δlmo1450, and Δlmo1722 revealed that FlhA, MotA, Lmo0866, Lmo1450, and Lmo1722 had roles in growth of L. monocytogenes EGD-e under cold stress conditions. The restricted growth of Δlmo0866 in 3.5% ethanol, and its increased maximum growth temperature and growth rate at 42.5°C, indicated that Lmo0866 had roles also in ethanol and heat stress tolerance of strain EGD-e. The role of Lmo1450 in the growth of strain EGD-e under heat, alkali, and oxidative stress conditions was shown by the restricted growth rate of Δlmo1450 at 42.5°C, in pH 9.4, and in 5 mM H2O2. The slightly decreased growth rate and maximum optical density of Δlmo1246 at 3°C indicated that the role of Lmo1246 in cold stress tolerance was negligible. Under all the other conditions, the growth of Δlmo1246 and the wild-type EGD-e were identical, suggesting that Lmo1246 had no role in growth of L. monocytogenes EGD-e under heat, pH osmotic, ethanol, or oxidative stress conditions. The deletion of flhA, motA, lmo0866, lmo1450, and lmo1722 impaired the motility of strain EGD-e, whereas the motility of Δlmo1246 did not differ from that of the wild type. This indicates that DEAD-box RNA helicases Lmo0866, Lmo1450, and Lmo1722 have roles in motility of strain EGD-e. Moreover, these results suggest that motility and cold stress tolerance of L. monocytogenes are linked, and that motile flagella may be needed for full cold stress tolerance of strain EGD-e.
  • Rautiainen, Henna (Helsingin yliopisto, 2008)
    Primary biliary cirrhosis (PBC) is caused by an autoimmune inflammation of the small bile ducts. It results to destruction of bile ducts, accumulation of the bile in the liver, and cirrhosis. The prevalence and incidence of PBC is increasing in the Western world. The prevalence is highest in the USA (402 per million) and incidence in Scotland (49/million/year). Our aim was to assess the epidemiology of PBC in Finland. Patients for the epidemiological study were searched from the hospital discharge records from year 1988 to 1999.The prevalence rose from 103 to 180/million from 1988 to 1999, an annual increase of 5.1%. The incidence rose from 12 to 17 /million/year, an annual increase of 3.5%. The age at death increased markedly from 65 to 76 years. The risk of liver related deaths diminished over time. The treatment of PBC is based on Ursodeoxycholic acid (UDCA). During 20 years 50% of patients end up with cirrhosis. Our treatment option was to combine budesonide, a potent corticosteroid with a high first pass metabolism in the liver, to UDCA and evaluate the liver effects and systemic effects such as bone mass density (BMD) changes. Our aim was to find out if combination of laboratory tests would serve as a surrogate marker for PBC and help reducing the need for liver biopsy. Non-cirrhotic PBC patients were randomized to receive budesonide 6 mg/day combined to UDCA 15 mg /kg/day or UDCA alone for three years. The combination therapy with UDCA and budesonide was effective: stage improved 22%, fibrosis 25%, and inflammation 32%. In the UDCA group the changes were: 20% deterioriation in stage and 70% in fibrosis, but a 10% improvement in inflammation. BMD in femoral neck decreased by 3.6% in the combination group and by 1.9% in the UDCA group. The reductions in lumbar spine were 2.8% and 0.7%. Pharmacokinetics did not differ between the stages of PBC. HA, PIIINP, bile acids, and AST were significantly different within stages I-III and could differentiate the mild fibrosis (F0F1) from the moderate (F2F3). The combination of these individual markers (PBC-score) further improved the accuracy. The area under the ROC of the PBC score, using a cut of value 66, had a sensitivity of 81.4% and a specificity of 65.2% to classify the stage of PBC. The prevalence of PBC in Finland increases, which results from increasing incidence and improved survival. The combination of budesonide and UDCA improves liver histology compared to UDCA alone in non-cirrhotic stages of PBC. The treatment may reduce BMD. Hyaluronic acid, PIIINP, AST, and bile acids may serve as tools to monitor the treatment response in the early stages of PBC. The budesonide and UDCA combination therapy is an option for those patients who do not receive full response from UDCA and are still at the non-cirrhotic stage of PBC.
  • Palo, Riikka (Helsingin yliopisto, 2013)
    Previously reported differences in transfusion practices suggest that transfusion protocols and clinical transfusion decisions may often be inappropriate. To change and monitor practices requires a follow-up system. A healthcare-integrated data-gathering system could provide the required information about blood use. The purpose of this observational study was to create a follow-up system for blood use and to gather information about transfused patients and transfusion practices in Finland. Data came from ten Finnish hospital districts (five university and five tertiary-care hospital districts) between the years 2002 and 2005. The collection process involved combining data from pre-existing electronic medical records applied for different purposes. This information was combined from these electronic systems by use of personal identification numbers and data expressed as hospital episodes. Variation in blood-use practices still existed between hospitals. For example, the percentage of red blood cell (RBC) receivers ranged in Finnish hospitals from 12% to 57% during primary knee-arthroplasty surgery. The most typical blood-transfused patient was an over 65-year-old woman receiving 2 units of RBCs. RBC products were usually transfused in pairs (such as in two-four-six units). In over 30% of FFP transfusions, plasma was given without any guidance from coagulation tests. Among moderately anemic parturients, transfusion of 0 to 2 units of RBC had no effect on length of hospitalization. Duration of hospitalization was, however, considerably longer in these anemic patients than for average Finnish mothers (5.2 days versus 3.5 days). Most of the platelet (PLT) products were transfused to hematological patients (43%). Only 1% of surgical patients received PLTs. Severity of underlying condition in surgical patients had an effect on prevalence of blood transfusions. Variability in blood-use practices suggests inappropriate blood use. Moreover, RBC transfusion in paired units is a questionable practice. FFP transfusions, not based on coagulation tests, suggest inappropriate use of plasma as well. In parturients, mild anemia treated with 1 to 2 units of RBCs does not shorten hospitalization time. This supports the current recommended thresholds for RBC transfusion. Improvement efforts concerning PLT-use practices may be directed to users of high doses of PLTs; to hematological patients, but also to digestive tract surgery and cardiac surgery patients. Knowledge of severity of the underlying disease as affecting the transfusion requirement may facilitate optimization of blood use.
  • Poikonen, Eira (Helsingin yliopisto, 2011)
    Candida species are an important cause of nosocomial bloodstream infections in hospitalized patients worldwide, with associated high mortality, excess length of stay and costs. Main contributors to candidemias is profound immunosuppression due to serious underlying condition or intensive treatments leading to an increasing number of susceptible patients. The rank order of causative Candida species varies over time and in different geographic locations. The aim of this study was to obtain information on epidemiology of candidemia in Finland, to identify trends in incidence, causative species, and patient populations at risk. In order to reveal possible outbreaks and assess the value of one molecular typing method, restriction enzyme analysis (REA), in epidemiological study, we analyzed C. albicans bloodstream isolates in Uusimaa region in Southern Finland during eight years. The data from the National Infectious Disease Register were used to assess the incidence and epidemiological features of candidemia cases. In Helsinki University Central Hospital (HUCH) all patients with blood culture yielding any Candida spp. were identified from laboratory log-books and from Finnish Hospital Infection Program. All the patients with a stored blood culture isolate of C. albicans were identified through microbiology laboratory logbooks, and stored isolates were genotyped with REA in the National Institute for Health and Welfare (former KTL). The incidence of candidemia in Finland is globally relatively low, but increased between between 1990s and 2000s. The incidence was highest in males >65 years of age, but incidence rates for patients <1-15 years were lower during 2000s than during 1990s. In HUCH the incidence of candidemia remained low and constant during our 18 years of observation, but a significant shift in patient-populations at risk was observed, associated with patients treated in intensive care units, such as premature neonates and surgical patients. The predominating causative species in Finland and in HUCH is C. albicans, but the proportion of C. glabrata increased considerably. The crude one-month case fatality was constantly high between 28-33%. REA differentiated efficiently between C. albicans blood culture isolates and no clusters were observed in the hospitals involved, despite of abundant transfer of patients among them. Candida spp. are an important cause of nosocomial blood stream infections in Finland, and continued surveillance is necessary to determine the overall trends and patient groups at risk, and reduce the impact of these infections in the future. Molecular methods provide an efficient tool for investigation of suspected outbreak and should be available in the future in Finland, also.
  • Kerola, Anne (Helsingin yliopisto, 2015)
    Rheumatoid arthritis (RA) is associated with a substantially increased risk for cardiovascular (CV) morbidity and mortality. Along with their CV burden, RA patients are at increased risk for other comorbidities such as hypothyroidism and depressive symptoms. The aim of this work was to evaluate the prevalence of CV comorbidities and hypothyroidism among RA patients in comparison to those of the general population at the time of RA diagnosis. We also aimed to determine, among patients with early RA, the contribution of psychiatric and CV comorbidities as causes of long-term work disability (WD). Lastly, we assessed CV mortality rates in early RA. Between 2000 and 2007, all patients diagnosed with RA in Finland were possible to identify from a Finnish nationwide register on special reimbursements for medicine expenses. The same register provided information on the presence of comorbidities antedating RA diagnosis. From the pension registers, we retrieved data on permanent or temporary disability pensions. Causes of death were obtainable until the end of 2008. We compared the main outcomes, that is, the prevalence of comorbidities at RA diagnosis, the incidence of comorbidity-related disability pensions, and CV mortality rates to those of the age- and sex-specific Finnish population, and calculated standardized rate, incidence and mortality ratios (SRRs, SIRs, and SMRs). In a population of 7,209 RA patients, the risk of having coronary heart disease (CHD) at RA diagnosis was slightly elevated, the SRR (95% CI) being 1.10 (1.01 1.20). The SRR for levothyroxine-treated hypothyroidism at RA diagnosis was 1.51 (1.35 to 1.67). SRR was highest, almost 2.5, among women with RA aged 20 to 49, the excess prevalence of hypothyroidism decreasing steadily and fading in older age groups. From 2000 to 2008, of 7,831 RA patients, 1,095 were granted a disability pension. The 9-year cumulative incidence of WD resulting from RA was 11.9%, from a psychiatric comorbidity 1.3%, and from a CV disease 0.5%. SIR of WD resulting from CV disease was 1.75 (1.23 to 2.51) and SIR of WD resulting from psychiatric disorders was 0.99 (0.80 to 1.23). By the end of 2008, of 14,878 RA patients, 1,157 had died, 501 (43%) from CV causes. The SMR in the entire RA cohort was 0.57 (0.52 0.62). To conclude, the risks for CHD and hypothyroidism were already higher among RA patients at RA diagnosis, highlighting the importance of CV risk detection and management and of vigilance for hypothyroidism. Psychiatric and CV comorbidities were the primary causes of long-term WD much less frequently than was RA itself; the risk for WD due to CV disease, however, was higher in RA than in the general population. During the era of modern treatment regimens for RA, the risk of CV death during the early years of RA was not elevated. All these findings together stress the importance of recognizing, preventing, and targeting comorbidities in RA, already in the early years of the disease.
  • Blomqvist, Soile (Helsingin yliopisto, 2004)
  • Perälä, Jonna (Helsingin yliopisto, 2013)
    Abstract: Schizophrenia and other psychoses are among the most severe mental disorders. There are few general population surveys of psychotic disorders. Most epidemiological studies have focused on schizophrenia and bipolar I disorder, while data of many other specific psychotic disorders are scarce. This study investigated the lifetime prevalence and epidemiological features of different psychotic disorders in the adult Finnish general population. The data were derived from the Health 2000 Study, a comprehensive general population survey of Finnish adults aged 30 years and over (N=8028). In the Psychoses in Finland study, the Health 2000 Study sample was screened for psychotic disorders. Those selected by the screens were invited for a mental health interview. Final best-estimate DSM-IV diagnoses were based on systematic evaluation of the interview and the case note data. The lifetime prevalence 3.5% of psychotic disorders was higher than has been estimated in most recent general population studies. The most common disorder was schizophrenia with lifetime prevalence 1%. Substance-induced psychotic disorders were common among working aged men and psychotic disorder due to general medical condition among women aged 65 years or over. Psychotic disorders were generally associated with socioeconomic disadvantage like being unmarried, pensioned or unemployed; having low income or education level. The highest lifetime prevalence of psychotic disorders was found in northern and eastern parts of Finland. The region of birth was a more important determinant of the risk of psychotic disorders than the region of residence, and most marked in schizophrenia. Alcohol-induced psychotic disorders were common in middle-aged men and associated with high morbidity and mortality. Clinical features of delusional disorder were different from schizophrenia. Disorganized schizophrenia was a schizophrenia subtype associated with poor outcome. With a high lifetime prevalence exceeding 3%, psychotic disorders are a major public health concern. The high and unevenly distributed prevalence should be taken into account when resources are allocated to health care.
  • Leino, Timo (Helsingin yliopisto, 2001)
  • Virtanen, Sonja (Helsingin yliopisto, 2014)
    Yersinia enterocolitica is a foodborne zoonotic pathogen. Among domestic animals, pigs are considered the major reservoir of Y. enterocolitica bioserotype 4/O:3. The pathogen is found in pig carcasses and pluck sets at slaughterhouses. Carcass contamination at the slaughterhouse originates from pigs that are already infected on farms. Considerable variation exists in the prevalence of Y. enterocolitica between different pig farms. The aim of this study was to determine the factors in farm management that can be used to prevent the presence and spread of this pathogen within and between farms. Multiple-locus variable-number tandem repeat analysis (MLVA) has been developed and used for genotyping of Y. enterocolitica strains of human origin. This genotyping method was used here to investigate its discriminatory ability, advantages and limitations, and use in genotyping Y. enterocolitica strains isolated from pigs. Among Y. enterocolitica 4/O:3 strains that originated from humans, pigs, and pork products from four European countries, the use of MLVA was found to have high discriminatory power. Similar MLVA types were detected among humans and pigs, human clinical isolates from limited geographical locations indicating the presence of past unidentified epidemics and also from pigs that originated from the same farms. MLVA proved to be able to detect farm-specific genotypes, but mild variation was common in strains originating from the same farms. Sampling of the farms revealed the spread of similar MLVA types among farms that had previously transported pigs between each other. Pigs were found to be a major source of transmission of this pathogen between all production types, including farrowing, farrow-to-finish, and fattening farms. Piglets from certain breeding farms served as a major source of infection for fattening pigs. These piglets carried farrowing farm-specific MLVA types of Y. enterocolitica to the fattening farm, and the infection spread throughout the fattening unit. Farm management practices and their association with carriage and shedding of Y. enterocolitica in pigs were studied by a purpose-designed questionnaire for farms whose pigs were previously sampled at slaughterhouses. The use of municipal water, organic production, and purchase of feed from a certain feed company were found to be protective factors against the carriage of Y. enterocolitica. In contrast, snout-to-snout contacts between pens and buying feed from another company were discovered as risk factors for fecal shedding of the pathogen. In total, 30 farms were further visited and sampled for enteropathogenic Yersinia, and the management practices and conditions were recorded during each sampling visit. The use of municipal water, the use of an all-in all-out system in the units of weaned piglets and fattening pigs, buying piglets from no more than one supplier at a time, and generous use of bedding were associated with lower prevalence of Y. enterocolitica on farms.
  • Ruotsalainen, Eeva (Helsingin yliopisto, 2006)
    Staphylococcus aureus is the second most common bloodstream isolate both in community- and hospital-acquired bacteremias. The clinical course of S. aureus bacteremia (SAB) is determined by its complications, particularly by the development of deep infections and thromboembolic events. Despite the progress of antimicrobial therapy, SAB is still associated with high mortality. However, injection drug users (IDUs) tend to have fewer complications and better prognosis than nonaddicts, especially in endocarditis. The present study was undertaken to investigate epidemiology, treatment and outcome of S. aureus bacteremia and endocarditis in Finland. In particular, differences in bacterial strains and their virulence factors, and host immune responses were compared between IDUs and nonaddicts. In Finland, 5045 SAB cases during 1995-2001 were included using the National Infectious Disease Register maintained by National Public Health Institute. The annual incidence of SAB increased, especially in elderly. While the increase in incidence may partly be explained by better reporting, it most likely reflects a growing population at risk, affected by such factors as age and/or severe comorbidity. Nosocomial infections accounted for 51% of cases, with no change in their proportion during the study period. The 28-day mortality was 17% and remained unchanged over time. A total of 381 patients with SAB were randomized to receive either standard antibiotic treatment or levofloxacin added to standard treatment. Levofloxacin combination therapy did not decrease the mortality, lower the incidence of deep infections, nor did it speed up the recovery during 3 months follow-up. However, patients with a deep infection appeared to benefit from combination therapy with rifampicin, as suggested also by experimental data. Deep infections were found in 84% of SAB patients within one week after randomization, and they appeared to be more common than previously reported. Endocarditis was observed in 74 of 430 patients (17%) with SAB, of whom 20 were IDUs and 54 nonaddicts. Right-sided involvement was diagnosed in 60% of addicts whereas 93% of nonaddicts had left-sided endocarditis. Unexpectedly, IDUs showed extracardiac deep infections, thromboembolic events and severe sepsis with the same frequency as nonaddicts. The prognosis of endocarditis was better among addicts due to their younger age and lack of underlying diseases in agreement with earlier reports. In total, all 44 IDUs with SAB were included and 20 of them had endocarditis. An equal number of nonaddicts with SAB were chosen as group matched controls. Serological tests were not helpful in identifying patients with a deep infection. No individual S. aureus strain dominated in endocarditis among addicts. Characterization of the virulence factors of bacterial strains did not reveal any significant differences in IDUs and nonaddicts.
  • Hakonen, Elina (Helsingin yliopisto, 2014)
    Pancreatic beta cells produce and secrete insulin into circulation in order to control blood glucose levels. The amount of beta cells is tightly controlled throughout life. If the number or function of beta cells is compromised, glucoregulation does not function properly, leading to dysglycemia. In the case of type 1 diabetes, beta cells are selectively targeted by an autoimmune attack, and die through apoptosis. Type 2 diabetes develops due to peripheral insulin resistance, combined with pancreatic beta cell failure. Individuals with type 2 diabetes show a reduced beta cell mass and increased beta cell apoptosis, leading to a relative lack of insulin. Treatments that replenish beta cell mass in diabetic patients could enable restoration of normal glycemic control and represent a potentially curative therapy. A better understanding of the factors that regulate or protect beta cell mass and function is important for the development of new treatments for all forms of diabetes. The major aim of the present study was to elucidate the role of epidermal growth factor receptor (EGFR) in beta cell mass regulation and protection against diabetogenic insults. Two mouse models were generated for these studies: one with downregulated EGFR signaling in beta cells through expression of a dominant-negative EGFR mutation, and the other with increased EGFR signaling through expression of constitutively active EGFR in beta cells. In the dominant-negative EGFR mouse model beta cell mass failed to expand during obesity and gestation, suggesting that EGFR signaling is crucial in beta cell mass regulation during these metabolic challenges. Subsequent mechanistic studies identified survivin as a candidate EGFR-regulated target mediating beta cell mass expansion during gestation. EGFR activation during the neonatal period led to increased beta cell proliferation and mass. In contrast, in adults EGFR activation had only a minor effect on beta cell proliferation and mass. Furthermore, EGFR activation protected beta cells against apoptosis in vivo during diabetogenic insults and in vitro when challenged with inflammatory cytokines. Mechanistic studies suggested that EGFR signaling protected isolated islets from cytokine-mediated beta cell death by repressing the proapoptotic protein Bim. In conclusion, EGFR signaling appears to be important in beta cell mass expansion during metabolic challenges. The observation that EGFR stimulation protects against experimental diabetes suggests that enhancing EGFR signaling could prevent or revert beta cell loss in diabetes.
  • Mezrar, Sari (nyk. Sari Wagner) (Helsingin yliopisto, 2010)
    Tämän tutkimuksen tarkoituksena on tarkastella epikleesirukouksia Sveitsin saksankielisten evankelis-reformoitujen kirkkojen ehtoollisliturgioissa. Tarkastelun kohteena on erityisesti kaksi asiaa: ensinnäkin tutkitaan epikleesirukousten kielellisiin rakenteisiin sisältyviä teologisia teemoja, toiseksi selvitetään epikleesirukousten teologianhistoriasta nousevia keskeisiä aiheita. Tutkimuksen metodina on systemaattinen analyysi. Tutkimuksen lähteenä käytetään Sveitsin saksankielisten evankelis-reformoitujen kirkkojen kirkkokäsikirjaa. Tutkimuksen historiallisessa taustaluvussa tarkastellaan eukaristisen rukouksen ja ehtoollisen syntyhistoriaa, eukaristisen rukouksen osia, epikleesin paikkaa, merkitystä ja roolia historiallisessa kontekstissa sekä erilaisia ehtoollisteologioita, ekumeenista liikettä ja liturgista uudistusta. Kolmannessa luvussa esitellään lyhyesti saksankielisen Sveitsin evankelis-reformoituja kirkkoja, niiden kirkkokäsikirjan syntyä ja rakennetta. Pääpaino on epikleeseissä, jotka ovat työssä sekä alkuperäisellä kielellään että työn tekijän laatimina suomennoksina. Neljäs ja viides luku liittyvät tutkimustehtävän ensimmäiseen osaan. Neljännessä luvussa Sveitsin saksankielisten evankelis-reformoitujen kirkkojen käsikirjan epikleesejä tarkastellaan objektin näkökulmasta ja verrataan muihin työssä esiin tuotuihin epikleeseihin. Viidennessä luvussa Sveitsin saksankielisten evankelis-reformoitujen kirkkojen epikleesien verbit ovat huomion keskipisteessä. Epikleesejä tarkastellaan niiden sisältäminen verbien näkökulmasta. Epikleesirukousten sisältämien verbien kirjoa tarkastellaan sekä määrällisesti että laadullisesti. Verbit luokitellaan kahteen luokkaan intentionsa perusteella. Epikleesien verbejä tarkastellaan myös niiden monipaikkaisuuden näkökulmasta. Kuudes luku liittyy tutkimustehtävän toiseen osaan. Kuudennessa luvussa epikleesejä tarkastellaan niiden sisältäminen teemojen näkökulmasta. Konsekraatio- ja kommuunioteemojen sisältö esitellään ja niiden esiintymistä tarkastellaan kaikissa työssä esiin tuoduissa epikleeseissä verraten Sveitsin saksankielisten evankelis-reformoitujen kirkkojen käsikirjan epikleesejä muissa työssä esiin tuotuihin epikleeseihin. Lisäksi nostetaan muutamia Sveitsin saksankielisten evankelis-reformoitujen kirkkojen käsikirjan epikleesien sisältämiä teemoja esiin. Loppukatsauksessa pyritään kokoamaan ja tiivistämään tutkimuksen olennaisimmat tulokset. Tutkimuksen tuloksena on, että Sveitsin saksankielisten evankelis-reformoitujen kirkkojen kirkkokäsikirja sisältää useita erilaisia ehtoollisliturgioita. Käsikirjan epikleesirukoukset poikkeavat toisistaan paljon niin rakenteellisesti kuin sisällöllisestikin. Kun sveitsiläisiä epikleesejä vertaa muiden kirkkojen epikleeseihin, niin joidenkin piirteiden suhteen kirjo on suurin piirtein yhtä laaja kuin muiden kirkkojen epikleeseissä yhteensä. On kuitenkin löydettävissä joitakin sveitsiläisille epikleeseille tyypillisiä piirteitä, kuten esimerkiksi, että sveitsiläiset epikleesit sisältävät aina selkeän puhuttelun kohteen tai että ehtoollisen koituminen hyödyksi ja siunaukseksi esiintyy teemana äärimmäisen harvoin. Sveitsin saksankielisten evankelis-reformoitujen kirkkojen kirkkokäsikirja antaa yksiselitteisesti kuvan rikkaasta ja monipuolisesta liturgisesta perinteestä, jossa liturgiaa ja liturgisia tekstejä ei pyritä mahduttamaan yhteen ainoaan muottiin, vaan erilaisuudelle löytyy tilaa.
  • Tarkiainen, Virpi (Helsingin yliopisto, 2013)
    Goals: The purpose of the study was to describe and analyse the content of online discussions and shared experiences among parents of children who suffer from epilepsy as well as parents' experiences with online peer support and its development. The goal was to deepen understanding of online peer support and the experiences of parents, and to develop the online activities of the Finnish Epilepsy Foundation based on the information gained. Previous studies about peer support have included group manifestations, personal experiences and peer support in community discussions. More and more peer support is available online, which has been seen in peer support studies from 2000 2009. Online peer support has been reported as both supporting and hindering empowering experiences. Previous studies have highlighted the significance of personal experiences. In this study, the concept of "experience" is defined from the standpoint of Dewey. Peer support is approached in the framework of empowerment. The study addresses four research questions. 1) What do parents of children with epilepsy write in online discussions? 2) What kind of experiences do they share in it? 3) What kind of experiences have parents had with online peer support, and which experiences further parents' empowerment? 4) How should online discussions be developed among parents? Methods: Study data was drawn from online discussions written by parents of children with epilepsy (the first message posted and the following message chain) and interviews with six (N = 6) parents who agreed to theme interviews. Web materials were written 15 June 13 December 2012. Data from theme interviews were gathered in February 2013 by interviewing parents by phone or in person. Web postings and interview content were handled using abductive content analysis, such that high rankings in the analysis utilised concepts of Siitonen's empowerment model (1999). Results and conclusions: The Internet offered parents of ill children an opportunity to share their experiences with other parents in similar life situations. In online discussions, parents shared their experiences about their children becoming ill, epilepsy treatments, support they had experienced as well as their emotions and mental images of the future. The significance of experiential data was highlighted in what parents wrote. Parents experienced the discussion environment as friendly, open, matter-of-fact and empathetic. From the standpoint of empowerment, it was significant that parents had the strength to support one another even in very difficult everyday life situations. The significance of experiences was affected by the environment of the online discussion, its content, parents' pre-conceived expectations as well as sharing emotional experiences and mental images of the future. Factors in the development of online discussions were related to briefing of the service, improved availability as well as active facilitation.