Yleisimmät perinnölliset verenvuototaudit ja niiden hoito

Opinnäytetyön tarkoituksena oli systemaattista kirjallisuuskatsausta soveltaen kartoittaa tietoa yleisimmistä perinnöllisistä verenvuototaudeista sekä niiden oireista ja hoidosta. Tavoitteena on kehittää perinnöllistä verenvuototautia sairastavan potilaan hoitotyötä terveydenhuollossa. Työ pohjautuu kahden eri hakuprosessin tuloksiin, tutkittavia julkaisuja oli yhteensä 32+16 (n=48). Yleisimmät perinnölliset verenvuototaudit ovat von Willebrandin tauti sekä hemofilia A ja B, jotka johtuvat hyytymistekijöiden vajeesta tai niiden toimintahäiriöstä. Hyytymistekijävajaukset aiheut-tavat vuotohäiriöitä, jolloin veren hyytyminen ei tapahdu kunnolla. Von Willebrandin taudissa tyypillisiä oireita ovat mustelmat, limakalvojen verenvuodot sekä naisien kohdalla myös runsaat kuukautiset. Hemofiliassa suuremmat verenvuodot ovat yleisempiä. Tyypillisiä hemofilian oireita ovat nivelten ja lihasten sisäiset verenvuodot spontaanisti tai vamman seurauksena. Vaikeissa tautimuodoissa yleensä annetaan suonensisäisesti hyytymistekijäkorvaushoitoa joko ennalta-ehkäisevästi tai tarvittaessa. Lievissä muodoissa voidaan käyttää myös muita hoitovaihtoehtoja. Vaikea-asteisessa sairaudessa ennaltaehkäisevä hoito on äärimmäisen tärkeää, jotta vältyttäi-siin tuki- ja liikuntaelimistön suuremmilta komplikaatioilta, joita ovat krooninen nivelkalvon tuleh-dus sekä nivelrikko. Verenvuototautien hoito on haasteellista ja kallista, ja siksi se tulisi keskittää asiantuntijayksik-köön, jossa potilaalla on mahdollisuus saada moniammatillinen yhteistyöverkosto ympärilleen. Keskittämisellä saavutetaan parempia ja kustannustehokkaampia hoitotuloksia. Verenvuototau-tien hoitoa tulisi kehittää perusterveydenhuollossa, varsinkin paikoissa, joissa potilaat tarvitsevat kiireellistä hoitoa. Näissä paikoissa henkilökunnalle tulisi järjestää lisäkoulutuksia verenvuoto-tauteihin liittyen. Hoidon toteutus on hoitohenkilökunnan vastuulla ja sen vuoksi myös näihin harvinaisiin sairauksiin tulisi perehtyä.The purpose of this systematic literature study was to obtain more information about the most common inherited bleeding disorders, their symptoms and treatment. The aim of this study was to help develop the treatment of patients with inherited bleeding disorders in public healthcare. This study was based on two different literature search processes. The number of publications used in this work was 32+16. (n=48) The most general inherited bleeding disorders are von Willebrand disease and hemophilia A and B, which are caused by deficiency of, or dysfunctional, coagulation factors. These coagula-tion factor defects cause bleeding disorders and therefor, the coagulation is abnormal. In von Willebrand disease, the most frequent symptoms are spontaneous or tissue injury-related mu-cocutaneous bleeding events. In women, the most common symptom is menorrahagia. In he-mophilia, major bleeding events are more common and the typical symptoms are spontaneous or injury-related joint and muscle bleeding. In severe disease, treatment is usually prophylactic or on-demand coagulation factor administration intravenously. In mild disease forms, also other treatments are possible. In severe disease, is necessary to avoid musculoskeletal complica-tions, such as arthrosis and synovitis. The treatment of these bleeding disorders should be im-proved especially in healthcare facilities, which are specialized in emergency treatment. These facilities should get further education about inherited bleeding disorders. The treatment of inherited bleeding disorders is both challenging and expensive. Therefore, the treatment should be focused to centers with hemophilic patients. In this way, the treatment would improve and become more cost-efficient. The patients need long-term treatment in facili-ties with expertise in many professional fields. The responsibility in the execution of the treat-ment is on the personnel and therefore, they should get proper education about these unusual diseases

Effects of lifelong ethanol consumption on brain monoamine transmitters in alcohol-preferring Alko Alcohol (AA) rats

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Thyroid function test variability and cardiovascular morbidity in hyperthyroidism

Objective: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. Design: Retrospective cohort study. Patients and Measurements: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8–2.0). The coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) -associated hospital visits were assessed with logistic regression analyses. Results: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03–1.09), male gender (OR: 2.33, 95% CI: 1.03–5.28) and fT4-CV (OR: 1.02, 95% CI: 1.01–1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14–0.61). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00–1.05). Conclusions: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs.Peer reviewe

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005–2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11–3320, vs. 45 ng/mL, range 15–529, vs. 32 ng/mL, range 3–213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers—that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005–2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11–3320, vs. 45 ng/mL, range 15–529, vs. 32 ng/mL, range 3–213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers—that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI

Insulinoomat Tampereen yliopistollisen sairaalan erityisvastuualueella 1980-2010

METHODS: Retrospective analysis of insulinomas diagnosed in Tampere University Hospital. RESULTS: We found 23 iNET cases corresponding to an incidence of 0.7/million/year. All had neuroglycopenic symptoms and 83% had autonomic ones. The median diagnostic delay (from first symptoms up to diagnosis) was 25 months. Preoperative imaging found the tumor in 87%. Twenty-one out of 22 patients who underwent surgery recovered completely. CONCLUSIONS: Despite improved imaging the diagnostic delay of iNETs remained unchanged. Hypoglycemia and insulinoma should be considered as a cause of unspecific, symptomatic attacks

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010

Objective Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. Design, patients and measurements The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as +/- 0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. Results Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 +/- 0.072 vs 0.903 +/- 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. Conclusions In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.Peer reviewe

Characteristics and Outcomes of 79 Patients with an Insulinoma : A Nationwide Retrospective Study in Finland

Objective. Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. Design and Methods. Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. Results. Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0 002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p <0 001). Seventy- one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. Conclusions. The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.Peer reviewe

Long-term morbidity and mortality in patients diagnosed with an insulinoma

Objective: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. Design: Retrospective cohort study. Methods: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. Results: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). Conclusions: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.publishedVersionPeer reviewe