Browsing by Subject "EPIDEMIOLOGY"

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  • Haghighi, Mona; Johnson, Suzanne Bennett; Qian, Xiaoning; Lynch, Kristian F.; Vehik, Kendra; Huang, Shuai; TEDDY Study Grp; Knip, Mikael (2016)
    Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
  • Hayes, A.; Nguyen, D.; Andersson, M.; Anton, A.; Bailly, J-L; Beard, S.; Benschop, K. S. M.; Berginc, N.; Blomqvist, S.; Cunningham, E.; Davis, D.; Dembinski, J. L.; Diedrich, S.; Dudman, S. G.; Dyrdak, R.; Eltringham, G. J. A.; Gonzales-Goggia, S.; Gunson, R.; Howson-Wells, H. C.; Jääskeläinen, A. J.; Lopez-Labrador, F. X.; Maier, M.; Majumdar, M.; Midgley, S.; Mirand, A.; Morley, U.; Nordbo, S. A.; Oikarinen, S.; Osman, H.; Papa, A.; Pellegrinelli, L.; Piralla, A.; Rabella, N.; Richter, J.; Smith, M.; Strand, A. Söderlund; Templeton, K.; Vipond, B.; Vuorinen, T.; Williams, C.; Wollants, E.; Zakikhany, K.; Fischer, T. K.; Harvala, H.; Simmonds, P. (2020)
    Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 mu L) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 mu L) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 x 10(-5)). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
  • Deelen, Joris; Kettunen, Johannes; Fischer, Krista; van der Spek, Ashley; Trompet, Stella; Kastenmueller, Gabi; Boyd, Andy; Zierer, Jonas; van den Akker, Erik B.; Ala-Korpela, Mika; Amin, Najaf; Demirkan, Ayse; Ghanbari, Mohsen; van Heemst, Diana; Ikram, M. Arfan; van Klinken, Jan Bert; Mooijaart, Simon P.; Peters, Annette; Salomaa, Veikko; Sattar, Naveed; Spector, Tim D.; Tiemeier, Henning; Verhoeven, Aswin; Waldenberger, Melanie; Wuertz, Peter; Smith, George Davey; Metspalu, Andres; Perola, Markus; Menni, Cristina; Geleijnse, Johanna M.; Drenos, Fotios; Beekman, Marian; Jukema, J. Wouter; van Duijn, Cornelia M.; Slagboom, P. Eline (2019)
    Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.
  • JSCRG; TSRHCCG (2018)
    Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 x 10(-20); odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.
  • Rapo-Pylkkö, Susanna; Haanpää, Maija; Liira, Helena (2017)
    Background: Chronic, mostly musculoskeletal pain is common among older adults. Little is known about the prognosis of chronic pain and the neuropathic pain qualities in older adults. We studied a cohort of community-dwelling older adults, clinically assessed their pain states, classified their type of pain (nociceptive, neuropathic or combined) and followed them up for a year. Methods: At baseline, a geriatrician clinically examined all study patients and classified their type of pain in collaboration with a pain specialist. Pain, quality of life and mental health were measured by questionnaires (BPI, GDS-15, BAI and SF-36) and reassessed after 1 year. Results: Despite chronic pain, all patients from the baseline cohort continued to live independently at 1 year. A total of 92 of 106 (87%) patients returned the follow-up questionnaire. Nociceptive pain on its own was present in 48 patients, whereas 44 patients also had neuropathic pain. Most patients (96%) had several pain states at baseline, and 13 patients reported a new pain state at follow-up. On average, there were no significant changes in the pain intensity, pain interference, mood or quality of life in either group between baseline and follow-up. Changes in pain were observed at the individual level, and both intensity and interference of pain at the follow-up had a negative correlation with the baseline value. Conclusions: On average, chronic pain was persistent in our patients, but they were able to live independently despite their pain. At the individual level, both relief and exacerbation of pain were observed, supporting the notion that pain is not inevitable and unremitting among older adults.
  • Äyräväinen, Leena; Heikkinen, Anna Maria; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Peltola, Jaakko; Suomalainen, Anni; Moilanen, Eeva; Hämäläinen, Mari; Laasonen, Leena; Meurman, Jukka H.; Leirisalo-Repo, Marjatta (2018)
    To study oral health in patients with rheumatoid arthritis (RA) with emphasis on disease activity and treatment of RA. In this prospective cohort study 81 RA patients [53 early untreated RA (EURA) and 28 chronic RA (CRA) patients with inadequate response to synthetic disease modifying antirheumatic drugs (DMARDs)], underwent rheumatological [Disease Activity Score (28-joint) DAS28] and dental examinations [Total Dental Index (TDI), Decayed Missing Filled Teeth (DMFT) and Decayed Missing Filled Surfaces (DMFS)]. For controls, 43 volunteers were examined. After the examinations, EURA patients started treatment with synthetic DMARDs, oral and intra-articular glucocorticoids. CRA patients were candidates for biological DMARDs. The patients were re-examined mean 16 months later. Results were analyzed with descriptive statistics and logistic regression. TDI was higher in both RA groups at baseline compared to controls [EURA: 2 (2-3); CRA: 2 (1-3); controls 1 (1-3), p = 0.045]. DMFT [r(s) 0.561 (p = 0.002)] and DMFS [r(s) 0.581 (p = 0.001)] associated with DAS28 at baseline in CRA patients. After follow-up, DAS28 associated positively with DMFT [r(s) 0.384 (p = 0.016)] and DMFS [r(s) 0.334 (p = 0.038)] in EURA patients; as well as in CRA patients DMFT [r (s) 0.672 (p = 0.001)], DMFS [r(s) 0.650 (p = 0.001)]. RA patients already in the early phase of the disease had poorer oral health compared to controls. The caries indices associated with the activity of RA in both patient groups. Oral status may thus contribute to the development and further relate to the activity of RA.
  • Dumuid, Dorothea; Stanford, Tyman E.; Pedisic, Zeljko; Maher, Carol; Lewis, Lucy K.; Martin-Fernandez, Josep-Antoni; Katzmarzyk, Peter T.; Chaput, Jean-Philippe; Fogelholm, Mikael; Standage, Martyn; Tremblay, Mark S.; Olds, Timothy (2018)
    Background: Daily activity data are by nature compositional data. Accordingly, they occupy a specific geometry with unique properties that is different to standard Euclidean geometry. This study aimed to estimate the difference in adiposity associated with isotemporal reallocation between daily activity behaviours, and to compare the findings from compositional isotemporal subsitution to those obtained from traditional isotemporal substitution. Methods: We estimated the differences in adiposity (body fat%) associated with reallocating fixed durations of time (isotemporal substitution) between accelerometer-measured daily activity behaviours (sleep, sedentary time and light and moderate-to-vigorous physical activity (MVPA)) among 1728 children aged 9-11 years from Australia, Canada, Finland and the UK (International Study of Childhood Obesity, Lifestyle and the Environment, 2011-2013).We generated estimates from compositional isotemporal substitution models and traditional non-compositional isotemporal substitution models. Results: Both compositional and traditional models estimated a positive (unfavourable) difference in body fat% when time was reallocated from MVPA to any other behaviour. Unlike traditional models, compositional models found the differences in estimated adiposity (1) were not necessarily symmetrical when an activity was being displaced, or displacing another (2) were not linearly related to the durations of time reallocated, and (3) varied depending on the starting composition. Conclusion: The compositional isotemporal model caters for the constrained and therefore relative nature of activity behaviour data and enables all daily behaviours to be included in a single statistical model. The traditional model treats data as real variables, thus the constrained nature of time is not accounted for, nor reflected in the findings. Findings from compositional isotemporal substitution support the importance of MVPA to children's health, and suggest that while interventions to increase MVPA may be of benefit, attention should be directed towards strategies to avoid decline in MVPA levels, particularly among already inactive children. Future applications of the compositional model can extend from pair-wise reallocations to other configurations of time-reallocation, for example, increasing MVPA at the expense of multiple other behaviours.
  • Murphy, Natalie A.; Arthur, Karissa C.; Tienari, Pentti J.; Houlden, Henry; Chio, Adriano; Traynor, Bryan J. (2017)
    A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients developing disease in their twenties and a small portion of carriers surviving to their ninth decade without developing symptoms. Describing penetrance by age among C9orf72 carriers and identifying parameters that alter onset age are essential to better understanding this locus and to enhance predictive counseling. To do so, data from 1,170 individuals were used to model penetrance. Our analysis showed that the penetrance was incomplete and age-dependent. Additionally, familial and sporadic penetrance did not significantly differ from one another; ALS cases exhibited earlier age of onset than FTD cases; and individuals with spinal-onset exhibited earlier age of onset than those with bulbar-onset. The older age of onset among female cases in general, and among female bulbar-onset cases in particular, was the most striking finding, and there may be an environmental, lifestyle, or hormonal factor that is influencing these penetrance patterns. These results will have important applications for future clinical research, the identification of disease modifiers, and genetic counseling.
  • Reusken, Chantal; Boonstra, Marrit; Rugebregt, Sharona; Scherbeijn, Sandra; Chandler, Felicity; Avsic-Zupanc, Tatjana; Vapalahti, Olli; Koopmans, Marion; GeurtsvanKessel, Corine H. (2019)
    Background: Tick-borne encephalitis (TBE) is an infectious disease endemic to large parts of Europe and Asia. Diagnosing TBE often relies on the detection of TBEV-specific antibodies in serum and cerebrospinal fluid (CSF) as viral genome is mostly not detectable once neurological symptoms occur. Objectives: We evaluated the performance of TBEV IgM and IgG ELISAs in both serum and CSF of confirmed TBEV patients and discuss the role of (CSF) serology in TBEV diagnostics. Study design: For the assay evaluation we collected specimen from confirmed TBEV patients. Assay specificity was assessed using sera from patients with a related flavivirus infection or other acute infection. A selected ELISA assay was used to analyze TBEV-specific antibodies in CSF and to evaluate the use in confirming TBE diagnosis. Results: In this study the overall sensitivity of the IgM TBEV ELISAs was acceptable (94-100 %). Four out of five IgM ELISA's demonstrated an excellent overall specificity from 94-100% whereas a low overall specificity was observed for the IgG TBEV ELISAs (30-71%). Intrathecal antibody production against TBEV was demonstrated in a subset of TBE patients. Conclusions: In four out of five ELISAs, IgM testing in serum and CSF of TBE patients is specific and confirmative. The lack of IgG specificity in all ELISAs emphasizes the need of confirmatory testing by virus neutralisation, depending on the patient's background and the geographic location of exposure to TBEV. A CSF-serum IgG antibody index can support the diagnosis specifically in chronic disease or once IgM has disappeared.
  • Majander, Kerttu; Pfrengle, Saskia; Kocher, Arthur; Neukamm, Judith; du Plessis, Louis; Pla-Diaz, Marta; Arora, Natasha; Akgul, Gulfirde; Salo, Kati; Schats, Rachel; Inskip, Sarah; Oinonen, Markku; Valk, Heiki; Malve, Martin; Kriiska, Aivar; Onkamo, Paivi; Gonzalez-Candelas, Fernando; Kuehnert, Denise; Krause, Johannes; Schuenemann, Verena J. (2020)
    Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidumin early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood.
  • Penttila, Tero; Makynen, Heikki; Hartikainen, Juha; Hyppola, Harri; Lauri, Timo; Lehto, Mika; Lund, Juha; Raatikainen, M. J. Pekka; FinFib2 Investigators (2017)
    Background: Atrial fibrillation (AF) is a common arrhythmia that causes numerous visits to emergency departments (ED). The aim of the FinFib2 study was to evaluate whether treatment of patients with AF in ED is consistent with the contemporary European Society of Cardiology (ESC) management guidelines. Here we report the results of antiarrhythmic drug therapy (AAD) in ED. Methods: All patients within the two-week study period whose primary reason for the ED visit was symptomatic AF were included into this prospective multicentre study. Comprehensive data on factors contributing to the treatment of AF were collected, including a data of previous use of ADDs, and changes made for them during a visit in ED. Results: The study population consisted of 1013 consecutive patients (mean age 70 +/- 13 years, 47.6% female). The mean European Heart Rhythm Association (EHRA) symptom score was 2.2 +/- 0.8. Rhythm control strategy was opt for 498 (63.8%) and 140 (64.5%) patients with previously and newly diagnosed AF, respectively. In patients with previously diagnosed AF the most frequently used AAD was a beta blocker (80.9%). Prior use of class I (11.4%) and III (9.1%) AADs as well as start or adjustment of their dosage (7.4%) were uncommon. Most of the patients with newly diagnosed AF were prescribed a beta blocker (71.0%) or a calcium channel antagonist (24.0%), and only two of them received class I or class III AADs. Conclusions: Our data demonstrated that in patients presenting to the ED with recurrent symptomatic AF and aimed for rhythm control strategy, the use of class I and class III AADs was rare despite ESC guideline recommendations. It is possible that early adaptation of a more aggressive rhythm control strategy might improve a quality of life for symptomatic patients and alleviate the ED burden associated with AF. Beta blockers were used by majority of patients as rate control therapy both in rate and rhythm control groups.
  • Yanes, Manar; Santoni, Giola; Maret-Ouda, John; Ness-Jensen, Eivind; Farkkila, Martti; Lynge, Elsebeth; Nwaru, Bright; Pukkala, Eero; Romundstad, Pal; Tryggvadottir, Laufey; von Euler-Chelpin, My; Lagergren, Jesper (2020)
    Introduction: Airway micro-aspiration might contribute to the proposed associations between gastroesophageal reflux disease (GERD) and some lung diseases, including lung cancer. This study aimed to examine the hypothesis that antireflux surgery decreases the risk of small cell carcinoma, squamous cell carcinoma and adenocarcinoma of the lung differently depending on their location in relation to micro-aspiration. Methods: Population-based cohort study including patients having undergone antireflux surgery during 1980-2014 in Denmark, Finland, Iceland, Norway or Sweden. Patients having undergone antireflux surgery were compared with two groups: 1) the corresponding background population, by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) and 2) non-operated GERD-patients, by calculating hazard ratios (HRs) with 95% CIs using multivariable Cox regression with adjustment for sex, age, calendar period, country, chronic obstructive pulmonary disease and obesity diagnosis or type 2 diabetes. Results: Among all 812,617 GERD-patients, 46,996 (5.8%) had undergone antireflux surgery. The SIRs were statistically significantly decreased for small cell carcinoma (SIR = 0.57, 95% CI 0.41-0.77) and squamous cell carcinoma (SIR = 0.75, 95% CI 0.60-0.92), but not for adenocarcinoma of the lung (SIR = 0.90, 95% CI 0.76-1.06). The HRs were also below unity for small cell carcinoma (HR = 0.63, 95% CI 0.44-0.90) and squamous cell carcinoma (HR = 0.80, 95% CI 0.62-1.03), but not for adenocarcinoma of the lung (HR = 1.03, 95% CI 0.84-1.26). Analyses restricted to patients with objective GERD (reflux oesophagitis or Barrett's oesophagus) showed similar results. Conclusions: This all-Nordic study indicates that patients who undergo antireflux surgery are at decreased risk of small cell carcinoma and squamous cell carcinoma of the lung, but not of adenocarcinoma of the lung. (C) 2020 The Author(s). Published by Elsevier Ltd.
  • Lietzen, Elina; GrÖnroos, Juha M.; Mecklin, Jukka-Pekka; Leppäniemi, Ari; Nordström, Pia; Rautio, Tero; Rantanen, Tuomo; Sand, Juhani; Paajanen, Hannu; Kaljonen, Anne; Salminen, Paulina (2019)
    PurposeAppendiceal tumors are rare, but high neoplasm rates have been reported at interval appendectomy after periappendicular abscess. Non-operative management of uncomplicated acute appendicitis has shown promising results. The data on appendiceal tumor incidence and presentation among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. Objective was to assess appendiceal tumor incidence and tumor association to appendicitis in patients with uncomplicated and complicated acute appendicitis.MethodsThis nationwide population-based registry study was conducted from 2007 to 2013. The Finnish Cancer Registry and the National Institute for Health Registry were used to combine data on all appendiceal tumors and acute appendicitis diagnosis with medical reports evaluated at eight study hospitals.ResultsAltogether, 840 appendiceal tumors were identified, and out of these, 504 patient reports were reviewed, including 472 patients in this study. Tumor was diagnosed at appendectomy for suspected acute appendicitis in 276 patients (58%). In the whole study, histologically acute appendicitis and tumor were both present in 53% (n=250), and out of these, 41% (n=102) were complicated and 59% (n=148) uncomplicated acute appendicitis. The associated tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated cases (3.24% vs. 0.87%, p
  • Wiersema, Renske; Koeze, Jacqueline; Hiemstra, Bart; Pettilä, Ville; Perner, Anders; Keus, Frederik; van der Horst, Iwan C. C.; SICS-I Study Grp; Clement, R. P.; Dieperink, W.; Hilbink, D. H.; Klasen, M.; Klaver, M.; Kaufmann, T.; Schokking, L. J.; Sikkens, V. W. (2019)
    Acute kidney injury (AKI) occurs in up to 50% of all critically ill patients and hemodynamic abnormalities are assumed to contribute, but their nature and share is still unclear. We explored the associations between hemodynamic variables, including cardiac index and right ventricular function, and the occurrence of AKI in critically ill patients. In this prospective cohort study, we included all patients acutely admitted to an intensive care unit (ICU). Within 24 h after ICU admission clinical and hemodynamic variables were registered including ultrasonographic measurements of cardiac index and right ventricular function, assessed using tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic excursion (RV S'). Maximum AKI stage was assessed according to the KDIGO criteria during the first 72 h after admission. Multivariable logistic regression modeling was used including both known predictors and univariable significant predictors of AKI. Secondary outcomes were days alive outside ICU and 90-day mortality. A total of 622 patients were included, of which 338 patients (54%) had at least AKI stage 1 within 72 h after ICU admission. In the final multivariate model higher age (OR 1.01, 95% CI 1.00-1.03, for each year), higher weight (OR 1.03 CI 1.02-1.04, for each kg), higher APACHE IV score (OR 1.02, CI 1.01-1.03, per point), lower mean arterial pressure (OR 1.02, CI 1.01-1.03, for each mmHg decrease) and lower TAPSE (OR 1.05, CI 1.02-1.09 per millimeter decrease) were all independent predictors for AKI in the final multivariate logistic regression model. Sepsis, cardiac index, RV S' and use of vasopressors were not significantly associated with AKI in our data. AKI patients had fewer days alive outside of ICU, and their mortality rate was significantly higher than those without AKI. In our cohort of acutely admitted ICU patients, the incidence of AKI was 54%. Hemodynamic variables were significantly different between patients with and without AKI. A worse right ventricle function was associated with AKI in the final model, whereas cardiac index was not.
  • Atrial Fibrillation Genetics Conso; Int Stroke Genetics Consortium; Pulit, Sara L.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Sinisalo, Juha; Vlachopoulou, Efthymia; Lokki, Marja-Liisa; Tatlisumak, Turgut; Happola, Olli (2018)
    Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. Methods We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. Results We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p <4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Conclusions Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
  • Guo, Qi; Burgess, Stephen; Turman, Constance; Bolla, Manjeet K.; Wang, Qin; Lush, Michael; Abraham, Jean; Aittomäki, Kristiina; Andrulis, Irene L.; Apicella, Carmel; Arndt, Volker; Barrdahl, Myrto; Benitez, Javier; Berg, Christine D.; Blomqvist, Carl; Bojesen, Stig E.; Bonanni, Bernardo; Brand, Judith S.; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Caldas, Carlos; Campa, Daniele; Canzian, Federico; Chang-Claude, Jenny; Chanock, Stephen J.; Chin, Suet-Feung; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Diver, W. Ryan; Dunning, Alison M.; Earl, Helena M.; Eccles, Diana M.; Ekici, Arif B.; Eriksson, Mikael; Evans, D. Gareth; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Flyger, Henrik; Gapstur, Susan M.; Gaudet, Mia M.; Giles, Graham G.; Muranen, Taru A.; Nevanlinna, Heli; kConFab AOCS Investigators (2017)
    There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13,P = 0.95). Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
  • Palmu, Samuel; Kuneinen, Susanna; Kautiainen, Hannu; Eriksson, Johan G.; Korhonen, Päivi E. (2021)
    Background and aims: Current guidelines on prediabetes and diabetes (T2D) recommend to regularly perform an oral glucose tolerance test (OGTT) on subjects at risk of T2D. However, it is not known why women tend to have relatively higher 2-h post-load plasma (2hPG) glucose concentrations during OGTT than men. The aim of the present study is to investigate if there are sex differences in fasting plasma glucose (FPG) and 2hPG concentrations in relation to body size in apparently healthy non-diabetic subjects with normal glucose tolerance. We hypothesized that sex differences in glucose tolerance are physiological and related to different body surface area (BSA) in men and women. Methods and results: A 2-h 75 g OGTT was performed on 2010 subjects aged 45-70 years. Their BSA was calculated using the Mosteller formula. Men and women were separately divided into five BSA levels. Within the normal 2hPG range, women had higher mean 2hPG concentrations during the OGTT than men in all BSA levels estimated by sex-standardized BSA (p for linearity < 0.001). BSA adjusted for age, waist circumference, leisure-time physical activity, and smoking, showed an inverse association with 2hPG concentration in both sexes. Mean FPG concentrations were higher in men than in women. Conclusions: Body size has a negative inverse association with 2hPG concentration in an OGTT even within a physiological plasma glucose range. This may cause underestimation of glucose disorders in individuals with larger BSA and overestimation in individuals with smaller BSA when using an OGTT. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (
  • Garcia-Romero, Noemi; Gonzalez-Tejedo, Carmen; Carrion-Navarro, Josefa; Esteban-Rubio, Susana; Rackov, Gorjana; Rodriguez-Fanjul, Vanessa; Oliver-De La Cruz, Jorge; Prat-Acin, Ricardo; Peris-Celda, Maria; Blesa, David; Ramirez-Jimenez, Laura; Sanchez-Gomez, Pilar; Perona, Rosario; Escobedo-Lucea, Carmen; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel (2016)
    Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas.
  • Rinne, Sanni J.; Sipilä, Lauri J.; Sulo, Päivi; Jouanguy, Emmanuelle; Beziat, Vivien; Abel, Laurent; Casanova, Jean-Laurent; Parvaneh, Nima; Balighi, Kamran; Guttman-Yassky, Emma; Sarid, Ronit; Aaltonen, Lauri A.; Aavikko, Mervi (2019)
    Familial clustering of classic Kaposi sarcoma (CKS) is rare with, approximately 100 families reported to date. We studied 2 consanguineous families, 1 Iranian and 1 Israeli, with multiple cases of adult CKS and without overt underlying immunodeficiency. We performed genome-wide linkage analysis and whole-genome sequencing to discover the putative genetic cause for predisposition. A 9-kb homozygous intronic deletion in RP11-259O2.1 in the Iranian family and 2 homozygous variants, 1 in SCUBE2 and the other in CDHR5, in the Israeli family were identified as possible candidates. The presented variants provide a robust starting point for validation in independent samples.
  • Irfan, Furqan B.; Consunji, Rafael; El-Menyar, Ayman; George, Pooja; Peralta, Ruben; Al-Thani, Hassan; Thomas, Stephen Hodges; Alinier, Guillaume; Shuaib, Ashfaq; Al-Suwaidi, Jassim; Singh, Rajvir; Castren, Maaret; Cameron, Peter A.; Djarv, Therese (2017)
    Background: Traumatic cardiac arrest studies have reported improved survival rates recently, ranging from 1.7-7.5%. This population-based nationwide study aims to describe the epidemiology, interventions and outcomes, and determine predictors of survival from out-of-hospital traumatic cardiac arrest (OHTCA) in Qatar. Methods: An observational retrospective population-based study was conducted on OHTCA patients in Qatar, from January 2010 to December 2015. Traumatic cardiac arrest was redefined to include out-of-hospital traumatic cardiac arrest (OHTCA) and in-hospital traumatic cardiac arrest (IHTCA). Results: A total of 410 OHTCA patients were included in the 6-year study period. The mean annual crude incidence rate of OHTCA was 4.0 per 100,000 population, in Qatar. OHTCA mostly occurred in males with a median age of 33. There was a preponderance of blunt injuries (94.3%) and head injuries (66.3%). Overall, the survival rate was 2.4%. Shockable rhythm, prehospital external hemorrhage control, in-hospital blood transfusion, and surgery were associated with higher odds of survival. Adrenaline (Epinephrine) lowered the odds of survival. Conclusion: The incidence of OHTCA was less than expected, with a low rate of survival. Thoracotomy was not associated with improved survival while Adrenaline administration lowered survival in OHTCA patients with majority blunt injuries. Interventions to enable early prehospital control of hemorrhage, blood transfusion, thoracostomy and surgery improved survival. (C) 2017 Elsevier B.V. All rights reserved.