The validity of rheumatoid arthritis diagnoses in Finnish biobanks

Objective The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. Method We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. Results The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. Conclusion These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.Peer reviewe

The validity of rheumatoid arthritis diagnoses in Finnish biobanks

Objective: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks.Method: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland.Results: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98.Conclusion: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.</p

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults

ObjectivesWe examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association.Materials and MethodsThis prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura.ResultsAfter adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS.ConclusionsAbdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.</p

Державне регулювання системи факторів оцінки та мінімізації ризиків легалізації коштів, одержаних злочинним шляхом в процесі фінансового моніторингу комерційних банків України

Основною ціллю данної статті є формулювання важливості впливу чітко визначених факторів, які впливають на процеси фінансового моніторингу в комерційних банків України. Виходячи з поставлених цілей, завданнями даної статті є розроблення моделі оцінки ризиків банківської установи щодо протидії легалізації коштів одержаних злочинним шляхом в системі внутрішньобанківського фінансового моніторингу, та використання в подальшому запропонованих стратегій управління наслідками даних ризиків

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient– control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

The influence of medication on the incidence, outcome, and recurrence of primary intracerebral hemorrhage

Abstract Intracerebral hemorrhage (ICH) is the most pernicious form of stroke, with high mortality. Warfarin-associated ICH (WA-ICH) carries an even higher mortality rate. The major reason for the high mortality is explained by early hematoma growth. Warfarin use has rapidly increased with the aging of the population. We investigated temporal trends in the incidence and outcome of WA-ICHs. We found that although the proportion of warfarin users almost quadrupled in our population, the annual incidence and case fatality of WA-ICHs decreased. Management of ICH is mostly supportive. Prevention of associated complications is the issue in improving outcome. Hypertension is the most important modifiable risk factor for primary ICH, but little is known of the effect of preceding hypertension on outcome. Aggressive lowering of blood pressure is suggested to be a feasible treatment option. Reversal of warfarin anticoagulation with prothrombin complex concentrate (PCC) has been implemented as an acute treatment option for patients with WA-ICH. We found that the survival of WA-ICH subjects among our population improved after implementation of reversal of warfarin anticoagulation with PCC, likely because of the introduction of PCC. Because high mean arterial blood pressure (BP) at admission is an independent predictor of early death in patients with ICH, we explored its role in survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension. We found that despite their higher BP values at admission, subjects with untreated hypertension showed better survival and more often a favorable outcome after BP-lowering therapy than other patients. Studies on recurrent ICH are scarce. Underlying comorbidities, prior strokes, and drug-induced impaired platelet function may increase the risk for primary ICH (PICH). A lobar location of primary ICH may predict recurrent ICH. We investigated whether these factors predicted recurrence of PICH. In our study the annual incidence of recurrent ICH was 1.67%. Cumulative 5- and 10-year incidences were 9.6% and 14.2%. In multivariable analyses, prior ischemic stroke and diabetes proved to be independent predictors for recurrence. Moreover, diabetes was an independent risk factor for fatal recurrent PICH. Use of aspirin and serotonergic drugs did not significantly contribute to the risk.Tiivistelmä Aivoverenvuoto (ICH) on aivoverenkiertohäiriöistä vakavin. Sille on tyypillistä korkea kuolleisuus erityisesti varfariinihoitoon liittyen, ja eloonjääneetkin vammautuvat usein vakavasti. Verenvuodon koon kasvu alkuvaiheessa selittänee korkean kuolleisuuden. Väestön ikääntymisen myötä varfariinin käyttö on lisääntynyt nopeasti. Aivoverenvuodon hoito perustuu pitkälti ennusteen parantamiseen komplikaatioita estämällä. Verenpaine on tärkein hoidettavissa oleva riskitekijä, mutta tutkimustieto akuutin vaiheen verenpainetason merkityksestä ennusteeseen on vähäistä. Tehokasta verenpaineen alentamista alkuvaiheessa pidetään lupaavana hoitomenetelmänä. Vuodon koon kasvua pyritään rajoittamaan kumoamalla varfariinin antikoaguloiva vaikutus protrombiinikompleksi-konsentraatilla (PCC). Väitöstyössäni selvitän varfariinin käyttöön liittyvien aivoverenvuotojen (WA-ICH) esiintymistiheyttä ja ennustetta ajan myötä. Tutkin myös vuodon koon kasvun rajoittamista ja alkuvaiheen korkean verenpaineen alentamista hoitomenetelminä sekä selvitän, mitkä tekijät johtavat ICH:n uusiutumiseen. Totesimme WA-ICH:n ilmaantuvuuden ja tapauskuolleisuuden pienentyneen, vaikka varfariinin käyttö miltei nelinkertaistui väestössämme. Toisaalta WA-ICH -potilaiden kuolleisuus pieneni PCC-hoidon aloittamisen jälkeen, mahdollisesti sen ansiosta. Tutkiessamme riippumattomasti varhaista kuolemaa ennustavan korkean tulovaiheen verenpaineen roolia normaaliverenpaineisilla, hoidettua ja hoitamatonta verenpainetautia sairastavilla totesimme hoitamattomien hypertonia-potilaiden selvinneen akuutin vaiheen lääkehoidon myötä muita useammin hengissä ja hyväkuntoisina korkeista tulovaiheen verenpainearvoista huolimatta. Aivoverenvuodon uusiutumiseen vaikuttavista tekijöistä on vähän tutkimustietoa. Muu sairastavuus, aiemmat aivoverenkiertohäiriöt ja trombosyyttien toimintaan vaikuttavat lääkkeet saattavat lisätä ICH:n uusiutumisriskiä. Totesimme vuosittaisen uuden ICH:n esiintymistiheyden olevan 1,67&#160;%. Aikaisempi aivoinfarkti ja diabetes osoittautuivat riippumattomiksi uusiutumista ennustaviksi riskitekijöiksi, minkä lisäksi diabetes ennusti kuolemaan johtavaa uutta ICH:a. Asetyylisalisyylihapon ja selektiivisten serotoniinin takaisinoton estäjien käyttäminen ei vaikuttanut merkittävästi uusiutumisriskiin