Browsing by Subject "PREVENTION"

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  • Peddinti, Gopal; Bergman, Michael; Tuomi, Tiinamaija; Groop, Leif (2019)
    Context: Early prediction of dysglycemia is crucial to prevent progression to type 2 diabetes. The 1-hour postload plasma glucose (PG) is reported to be a better predictor of dysglycemia than fasting plasma glucose (FPG), 2-hour PG, or glycated hemoglobin (HbA1c). Objective: To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and PG and serum insulin (INS) levels during a 75-g oral glucose tolerance test (OGTT). Design and Setting: We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 participants in the Botnia Prospective Study, 146 of whom progressed to type 2 diabetes within a 10-year follow-up period. Using combinations of variables, we evaluated 1527 predictive models for progression to type 2 diabetes. Results: The 1-hour PG outperformed every individual marker except 30-minute PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c was inferior to 1-hour PG according to DeLong test P value but not false discovery rate. Combining the metabolic markers with PG measurements and HbA1c significantly improved the predictive models, and mannose was found to be a robust metabolic marker. Conclusions: The 1-hour PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes, outperforms the 2-hour PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-g OGTT to 1 hour improves its predictive value and clinical usability.
  • Uusi-Rasi, Kirsti; Patil, Radhika; Karinkanta, Saija; Kannus, Pekka; Tokola, Kari; Lamberg-Allardt, Christel; Sievanen, Harri (2017)
    Background: Both exercise and vitamin D are recommended means to prevent falls among older adults, but their combined effects on fallinduced injuries are scarcely studied. Methods: A 2-year follow-up of a previous 2-year randomized controlled trial with vitamin D and exercise (Ex) of 409 older home-dwelling women using a factorial 2 x 2 design (D(-)Ex(-), D(+)Ex(-), D(-)Ex(+), D(+)Ex(+)). Besides monthly fall diaries, femoral neck bone mineral density (fn-BMD), and physical functioning were assessed at 1 and 2 years after the intervention. Results: After the intervention, S-25OHD concentrations declined to baseline levels in both supplement groups. The groups did not differ for change in fn-BMD or physical functioning, except for leg extensor muscle strength, which remained about 10% greater in the exercise groups compared with the reference group (D(-)Ex(-)). There were no between-group differences in the rate of all falls, but medically attended injurious falls reduced in D+ Ex-and D(-)Ex(+) groups compared with D(-)Ex(-). However, all former treatment groups had less medically attended injured fallers, HRs (95% CI) being 0.62 (0.39-1.00) for D+ Ex-, 0.46 (0.28-0.76) for D(-)Ex(+), and 0.55 (0.34-0.88) for D(+)Ex(+), compared with D(-)Ex(-). Conclusions: Exercise-induced benefits in physical functioning partly remained 2 years after cessation of supervised training. Although there was no difference in the rate of all falls, former exercise groups continued to have lower rate of medically attended injured fallers compared with referents even 2 years after the intervention. Vitamin D without exercise was associated with less injurious falls with no difference in physical functioning.
  • Bjornland, Kristin; Pakarinen, Mikko P.; Stenstrom, Pernilla; Stensrud, Kjetil J.; Neuvonen, Malla; Granström, Anna L.; Graneli, Christina; Pripp, Are H.; Arnbjörnsson, Einar; Emblem, Ragnhild; Wester, Tomas; Rintala, Risto J.; Nordic Pediat Surgery Study Consor (2017)
    Objective: Transanal endorectal pull-through (ERPT) is the most popular technique to treat Hirschsprung disease (HD). Still, there is limited knowledge on long-term bowel function. This cross-sectional, multicenter study assessed long-term bowel function in a large HD population and examined predictors of poor outcome. Methods: Patients older than four years or their parents filled out a validated questionnaire on bowel function. Clinical details were recorded retrospectively from medical records. Results: 73/200 (37%) patients reported absolutely no impaired bowel function, meaning no constipation, fecal accidents, stoma, appendicostomy or need for enemas. Seven (4%) had a stoma, and 33 (17%) used antegrade or rectal colonic enemas. Most disarrangements of fecal control and constipation were significantly less common in older age group, but abnormal defecation frequency and social problems remained unchanged. Syndromic patients (n = 31) experienced frequent fecal accidents (46%) more often than nonsyndromic (14%, P <0.001). Having a syndrome (adjusted OR 5.6, 95% CI 2.1-15, P = 0.001) or a complete transanal ERPT (adjusted OR 2.4, 95% CI 1.1-5.7, P = 0.038) was significantly associated with poor outcome defined as having a stoma, an appendicostomy, daily fecal accidents or need of regular rectal wash outs. Conclusion: A significant number of HD patients experience bowel problems many years after definite surgery. Fecal control was significantly better in older than younger HD patients, but some continued to have considerable bowel problems also as adults. A total transanal ERPT was associated with poorer outcome. Long-term follow-up of HD patients is warranted. (C) 2017 Elsevier Inc. All rights reserved.
  • Kössi, Jyrki; Julkunen, Kristiina; Setälä, Marjaleena; Luostarinen, Markku (2016)
    Icodextrin (AdeptA (R)) has been shown to prevent postoperative adhesions in experimental and laparoscopic adhesiolysis surgery. However, the role of icodextrin in the prevention of adhesions in extensive gynecological surgery is unclear. The present study evaluated the effect of icodextrin on adhesion-related readmissions after extensive gynecological surgery. The hospital readmissions of 140 endometriosis patients operated on at Paijat-Hame Central Hospital in 2004-2008 with the use of icodextrin were retrospectively reviewed. The evaluation of readmissions focused on adhesion-related disorders and reoperations. If an abdominal or pelvic reoperation was performed, the extent of the adhesions was classified. The mean follow-up time was 6.53 years (range 0.21-9.83). After initial surgery, one patient (0.7 %) had adhesive small bowel obstruction. Another directly adhesion-related readmission occurred in two patients (1.4 %). The number of readmissions possibly related to adhesions was 3 (2.1 %). Abdominal or pelvic reoperation was performed on 54 patients (38.6 %): 4 in the open surgery group and 50 in the laparoscopic surgery group. The extent of the adhesions among the 54 reoperated patients was as follows: not mentioned in 16 patients, no adhesions in 14, mild in 18, moderate in 5, and severe in 1. There were two (3.7 %) bowel injuries (one enterotomy and one serosal lesion) in reoperations. The incidence of adhesion-related readmissions after the use of icodextrin is relatively low. This favorable result may be partly related to the laparoscopic technique. Despite the use of an anti-adhesion agent, in some patients, the extent of postoperative adhesions is severe.
  • Vuorio, Alpo; Laukkala, Tanja; Junttila, Ilkka; Bor, Robert; Budowle, Bruce; Pukkala, Eero; Navathe, Pooshan; Sajantila, Antti (2018)
    Pilot aircraft-assisted suicides (AAS) are rare, and there is limited understanding of copycat phenomenon among aviators. The aim of this study was to evaluate the possible effect the 11 September 2001, terrorist attacks had on pilot AASs in the U.S. Fatal aviation accidents in the National Transportation Safety Board (NTSB) database were searched using the following search words: "suicide", "murder-suicide" and "homicide-suicide". The timeline between 11 September 1996, and 11 September 2004, was analyzed. Only those accidents in which NTSB judged that the cause of the accident was suicide were included in the final analysis. The relative risk (RR) of the pilot AASs in all fatal accidents in the U.S. was calculated in order to compare the one, two, and three-year periods after the September 11 terrorist attacks with five years preceding the event. The RR of a fatal general aviation aircraft accident being due to pilot suicide was 3.68-fold (95% confidence interval 1.04-12.98) during the first year after 11 September 2001, but there was not a statistically significant increase in the later years. This study showed an association, albeit not determinate causal effect, of a very specific series of simultaneous terrorist murder-suicides with subsequent pilot AASs.
  • Violette, Philippe D.; Vernooij, Robin W. M.; Aoki, Yoshitaka; Agarwal, Arnav; Cartwright, Rufus; Arai, Yoichi; Tailly, Thomas; Novara, Giacomo; Baldeh, Tejan; Craigie, Samantha; Breau, Rodney H; Guyatt, Gordon H.; Tikkinen, Kari (2021)
    Background: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized. Objective: To characterize international practice variation in thromboprophylaxis use in urological surgery. Design, setting, and participants: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice. Outcome measurements and statistical analysis: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use. Results and limitations: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan.
  • Noronen, Katariina; Saarinen, Eva; Albäck, Anders; Venermo, Maarit (2017)
    Objectives: The number of elderly people is increasing; inevitably, the result will be more patients with critical limb ischaemia (CLI) in the future. Tissue loss in CLI is related to a high risk of major amputation. The aim of this study was to analyze the treatment process from referral to revascularisation, to discover possible delays and reasons behind them, and to distinguish patients benefitting the most from early revascularisation. Methods: A retrospective analysis was performed of 394 consecutive patients with a combined 447 affected limbs, referred to the outpatient clinic during 2010-2011 for tissue loss of suspected ischaemic origin. Results: For 246 limbs revascularisation was scheduled. After changes in the initial treatment strategy, endovascular treatment (ET) was performed on 221 and open surgery (OS) on 45 limbs. Notably there was crossover after ET in 17.0% of the procedures, and re-revascularisations were required in 40.1% after ET and 31.1% after OS. The median time from referral to revascularisation was 43 days (range 1-657 days) with no significant difference between ET and OS. For 29 (11.8%) patients the ischaemic limb required an emergency operation scheduled at the first visit to the outpatient clinic. For 25 (10.2%) patients the situation worsened while waiting for elective revascularisation and an emergency procedure was performed. Diabetic patients formed the majority of the study population; with 159 diabetic feet undergoing revascularisation. In multivariate analysis, diabetes was associated with poor limb salvage. When revascularisation was achieved within 2 weeks, no difference was seen in limb salvage. However, when the delay from first visit to revascularisation exceeded 2 weeks, limb salvage was significantly poorer in diabetic patients. Conclusions: Diabetic ulcers always require vascular evaluation, and when.ischaemia is suspected the diagnostics should be organised rapidly to ensure revascularisation without delay, according to this study within 2 weeks from the first evaluation. (C) 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
  • Hecht, Idan; Karesvuo, Petteri; Achiron, Asaf; Elbaz, Uri; Laine, Ilkka; Tuuminen, Raimo (2020)
    Purpose To assess the role of anti-inflammatory medication following cataract surgery on the formation of posterior capsular opacification. Design Cohort study. Methods A retrospective registry analysis of 25,818 consecutive cases who underwent cataract surgery between the years 2014 and 2018 at Helsinki University Hospital in Finland. Nd:YAG laser capsulotomy rates were compared between patients treated postoperatively with topical steroids, non-steroidal anti-inflammatory medications (NSAIDs), or their combination. Kaplan-Meier and Cox regression analyses were used. A single eye of each patient was included. Main outcomes were confirmed against a second independent dataset. Results 13,368 patients were included in the analysis with a mean age of 73.2±9.7 years and 61.7% were female. Pseudoexfoliation was noted in 10.1% of cases. The mean follow-up time was 22.8±15.7 months. Patients were treated with steroid monotherapy (28.9% of cases), NSAIDs monotherapy (62.2%), or a combination of both (8.9%). Treatment with steroids resulted in significantly lower Nd:YAG capsulotomy rates compared to NSAIDs (HR 0.76, 95% CI 0.62-0.93, P=0.009). Treatment with combination therapy of steroids and NSAIDs showed no added benefit over steroid monotherapy (HR 1.11, 95% CI 0.68-1.80, P=0.674). Cox regression analysis adjusted for patients’ age, gender, pseudoexfoliation, and risk stratification remained significantly predictive for lower capsulotomy rates with steroid treatment over NSAIDs (HR 0.70, 95% CI 0.52-0.88, P=0.001). Conclusions Postoperative treatment with steroids among patients undergoing uncomplicated cataract surgery was associated with lower rates of clinically significant posterior capsule opacification compared to treatment with NSAIDs alone. Combination therapy of steroids and NSAIDs had no added benefit over steroids alone.
  • Ylinen, Petteri; Holmstrom, Emil; Laine, Ilkka; Lindholm, Juha-Matti; Tuuminen, Raimo (2018)
    PurposeTo examine the anti-inflammatory efficacy and tolerance between preservative-free dexamethasone (DEX) and diclofenac (DICL) eye drops, and their combination following cataract surgery. MethodsA randomized, double-blind, prospective single-centre study with 189 eyes of 180 patients undergoing routine cataract surgery. Laser flare meter measurement and spectral-domain optical coherence tomography imaging were conducted before surgery and at the 28-day postoperative visit. Clinical characteristics, surgical parameters and assessment of postoperative symptoms were recorded. ResultsPreoperative flare was 9.00.6pu/ms and central retinal thickness (CRT) 269.6 +/- 1.9m (mean +/- SEM). On day 28, flare was 22.1 +/- 2.9 pu/ms for DEX, 17.4 +/- 2.5pu/ms for DICL and 13.0 +/- 1.6pu/ms (p ConclusionDiclofenac (DICL), as well as the combination of DEX and DICL, were superior to DEX monotherapy in minimizing CRT change and the incidence of PCME. Combination medication showed no added value compared to DICL monotherapy in uneventful cataract surgery.
  • Välkki, Kirsi Johanna; Thomson, Katariina Hanne; Grönthal, Thomas Sven Christer; Junnila, Jouni Juho Tapio; Rantala, Merja Hilma Johanna; Laitinen-Vapaavuori, Outi Maria; Mölsä, Sari Helena (2020)
    Background Surgical site infections (SSI) are associated with increased morbidity and mortality. To lower the incidence of SSI, antimicrobial prophylaxis is given 30-60 min before certain types of surgeries in both human and veterinary patients. However, due to the increasing concern of antimicrobial resistance, the benefit of antimicrobial prophylaxis in clean orthopaedic and neurosurgeries warrants investigation. The aims of this retrospective cross-sectional study were to review the rate of SSI and evaluate the compliance with antimicrobial guidelines in dogs at a veterinary teaching hospital in 2012-2016. In addition, possible risk factors for SSI were assessed. Results Nearly all dogs (377/406; 92.9%) received antimicrobial prophylaxis. Twenty-nine dogs (7.1%) did not receive any antimicrobials and only four (1.1%) received postoperative antimicrobials. The compliance with in-house and national protocols was excellent regarding the choice of prophylactic antimicrobial (cefazolin), but there was room for improvement in the timing of prophylaxis administration. Follow-up data was available for 89.4% (363/406) of the dogs. Mean follow-up time was 464 days (range: 3-2600 days). The overall SSI rate was 6.3%: in orthopaedic surgeries it was 6.7%, and in neurosurgeries it was 4.2%. The lowest SSI rates (0%) were seen in extracapsular repair of cranial cruciate ligament rupture, ulnar ostectomy, femoral head and neck excision, arthrotomy and coxofemoral luxation repair. The highest SSI rate (25.0%) was seen in arthrodesis. Omission of antimicrobials did not increase the risk for SSI (P = 0.56; OR 1.7; CI(95%)0.4-5.0). Several risk factors for SSI were identified, including methicillin-resistantStaphylococcus pseudintermediuscarriage (P = 0.02; OR 9.0; CI(95%)1.4-57.9) and higher body temperature (P = 0.03; OR 1.69; CI(95%)1.0-2.7; mean difference + 0.4 degrees C compared to dogs without SSI). Conclusions Antimicrobial prophylaxis without postoperative antimicrobials is sufficient to maintain the overall rate of SSI at a level similar to published data in canine clean orthopedic and neurosurgeries.
  • Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Vestentoft, Pia Siig; Brand-Miller, Jennie C.; Jalo, Elli; Westerterp-Plantenga, Margriet; Simpson, Elizabeth J.; Handjieva-Darlenska, Teodora; Stratton, Gareth; Huttunen-Lenz, Maija; Lam, Tony; Muirhead, Roslyn; Poppitt, Sally; Pietiläinen, Kirsi H.; Adam, Tanja; Taylor, Moira A.; Handjiev, Svetoslav; McNarry, Melitta A.; Hansen, Sylvia; Brodie, Shannon; Silvestre, Marta P.; Macdonald, Ian A.; Boyadjieva, Nadka; Mackintosh, Kelly A.; Schlicht, Wolfgang; Liu, Amy; Larsen, Thomas M.; Fogelholm, Mikael; Raben, Anne; Alfredo Martinez, J. (2021)
    Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) x fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs.Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve & GE;8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures.Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity.Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D.
  • Gholami, Mahdia; Pakdaman, Afsaneh; Montazeri, Ali; Jafari, Ahmad; Virtanen, Jorma I. (2014)
  • SECRETO Study Grp; Martinez-Majander, Nicolas; Artto, Ville; Ylikotila, Pauli; von Sarnowski, Bettina; Huhtakangas, Juha; Numminen, Heikki; Jäkälä, Pekka; Putaala, Jukka (2021)
    Objective To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). Methods We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (+/- 5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. Results The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. Interpretation MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2020
  • Krischer, Jeffrey P.; Cuthbertson, David; Couluris, Marisa; Knip, Mikael; Virtanen, Suvi M. (2020)
    Aims/hypothesis This paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema. Methods A total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10 years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9-11 years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity. Results The cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9-11 years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together. Conclusions/interpretation The findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first.
  • Griffiths, Amanda; Kouvonen, Anne; Pentti, Jaana; Oksanen, Tuula; Virtanen, Marianna; Salo, Paula; Vaananen, Ari; Kivimaki, Mika; Vahtera, Jussi (2014)
  • Penack, Olaf; Peczynski, Christophe; van der Werf, Steffie; Finke, Juergen; Ganser, Arnold; Schoemans, Helene; Pavlu, Jiri; Niittyvuopio, Riitta; Schroyens, Wilfried; Kaynar, Leylagul; Blau, Igor W.; van der Velden, Walter; Sierra, Jorge; Cortelezzi, Agostino; Wulf, Gerald; Turlure, Pascal; Rovira, Montserat; Ozkurt, Zubeydenur; Pascual-Cascon, Maria J.; Moreira, Maria C.; Clausen, Johannes; Greinix, Hildegard; Duarte, Rafael F.; Basak, Grzegorz W. (2020)
    Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline co-morbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0-2.4, P=0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7-4.7, P
  • Fuertes, Elaine; Soderhall, Cilla; Acevedo, Nathalie; Becker, Allan; Brauer, Michael; Chan-Yeung, Moira; Dijk, F. Nicole; Heinrich, Joachim; de Jongste, Johan; Koppelman, Gerard H.; Postma, Dirkje S.; Kere, Juha; Kozyrskyj, Anita L.; Pershagen, Goran; Sandford, Andrew; Standl, Marie; Tiesler, Carla M. T.; Waldenberger, Melanie; Westman, Marit; Carlsten, Christopher; Melen, Erik (2015)
  • Stephen, Ruth; Liu, Yawu; Ngandu, Tiia; Rinne, Juha O.; Kemppainen, Nina; Parkkola, Riitta; Laatikainen, Tiina; Paajanen, Teemu; Hanninen, Tuomo; Strandberg, Timo; Antikainen, Riitta; Tuomilehto, Jaakko; Keinanen Kiukaanniemi, Sirkka; Vanninen, Ritva; Helisalmi, Seppo; Levalahti, Esko; Kivipelto, Miia; Soininen, Hilkka; Solomon, Alina (2017)
    Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta- coefficient -0.29, p = 0.001) and hippocampal volume (beta- coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p <0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15,95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.
  • Neuvonen, Elisa; Lehtisalo, Jenni; Ngandu, Tiia; Levälahti, Esko; Antikainen, Riitta; Hänninen, Tuomo; Laatikainen, Tiina; Lindström, Jaana; Paajanen, Teemu; Soininen, Hilkka; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia; Solomon, Alina (2022)
    Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60-77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group x time coefficient -0.006, 95% CI -0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (-0.140, p = 0.005) and memory (-0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung >= 40 points) had less intervention benefit to executive functioning (group x time x Zung -0.096, 95% CI -0.163 to -0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions.
  • 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.