Browsing by Subject "CRITERIA"

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  • Jalanko, Mikko; Heliö, Tiina; Mustonen, Pirjo; Kokkonen, Jorma; Huhtala, Heini; Laine, Mika; Jääskeläinen, Pertti; Tarkiainen, Mika; Lauerma, Kirsi; Sipola, Petri; Laakso, Markku; Kuusisto, Johanna; Nikus, Kjell (2018)
    Objectives: The sensitivity and specificity of the conventional 12-lead ECG to identify carriers of hypertrophic cardiomyopathy (HCM) - causing mutations without left ventricular hypertrophy (LVH) has been limited. We assessed the ability of novel electrocardiographic parameters to improve the detection of HCM mutation carriers. Methods: We studied 140 carriers (G+) of the TPM7-Asp175Asn or MYBPC3-Glnl 061X pathogenic variants for HCM: The G+/LVH+ group (n = 98) consisted of mutation carriers with LVH and the G+/LVH- group (n = 42) without LVH. The control group consisted of 30 subjects. The standard 12-lead ECG was comprehensively analyzed and two novel ECG variables were introduced: RVlRV3 and septal remodeling. A subset of 65 individuals underwent cardiac magnetic resonance imaging and 2D strain echocardiography. Results: Conventional major ECG criteria were sensitive (90%) and specific (97%) in identifying G+/LVH+ subjects. RV1RV3 and septal remodeling were more prevalent in the G+/LVH- subjects compared to the control group (33% vs 3%, p = 0.005 and 45% vs 3%, p <0.001, respectively). The combination of RVlRV3 and Q waves and repolarization abnormalities (QR) differentiated between the G+/LVH- subjects and the control group with a sensitivity of 52% and specificity of 97%. The combination of septa] remodeling and QR differentiated between G+/LVH- subjects and the control group with a sensitivity of 64% and specificity of 97%. Conclusions: The novel ECG-parameters RVlRV3 and septal remodeling were effective in identifying G+/LVH-subjects and could be useful in the diagnostics of new suspected HCM patients and in the screening and follow-up of HCM families. (C) 2018 Elsevier Inc. All rights reserved.
  • Hemminki, Otto; Oksanen, Minna; Taipale, Kristian; Liikanen, Ilkka; Koski, Anniina; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli (2018)
    The first US Food and Drug Administration (FDA)- and EMA-approved oncolytic virus has been available since 2015. However, there are no markers available that would predict benefit for the individual patient. During 2007-2012, we treated 290 patients with advanced chemotherapy-refractory cancers, using 10 different oncolytic adenoviruses. Treatments were given in a Finnish Medicines Agency (FIMEA)-regulated individualized patient treatment program (the Advanced Therapy Access Program [ATAP]), which required long-term follow-up of patients, which is presented here. Focusing on the longest surviving patients, some key clinical and biological features are presented as "oncograms." Some key attributes that could be captured in the oncogram are suggested to predict treatment response and survival after oncolytic adenovirus treatment. The oncogram includes immunological laboratory parameters assessed in peripheral blood (leukocytes, neutrophil-to-lymphocyte ratio, interleukin-8 [IL-81, HMGB1, antiviral neutralizing antibody status), features of the patient (gender, performance status), tumor features (histological tumor type, tumor load, region of metastases), and oncolytic virus-specific features (arming of the virus). The retrospective approach used here facilitates verification in a prospective controlled trial setting. To our knowledge, the oncogram is the first holistic attempt to identify the patients most likely to benefit from adenoviral oncolytic virotherapy.
  • Juutinen, Milla; Wang, Cassia; Zhu, Justin; Haladjian, Juan; Ruokolainen, Jari; Puustinen, Juha; Vehkaoja, Antti (2020)
    Parkinson’s disease (PD) is a neurodegenerative disease inducing dystrophy of the motor system. Automatic movement analysis systems have potential in improving patient care by enabling personalized and more accurate adjust of treatment. These systems utilize machine learning to classify the movement properties based on the features derived from the signals. Smartphones can provide an inexpensive measurement platform with their built-in sensors for movement assessment. This study compared three feature selection and nine classification methods for identifying PD patients from control subjects based on accelerometer and gyroscope signals measured with a smartphone during a 20-step walking test. Minimum Redundancy Maximum Relevance (mRMR) and sequential feature selection with both forward (SFS) and backward (SBS) propagation directions were used in this study. The number of selected features was narrowed down from 201 to 4–15 features by applying SFS and mRMR methods. From the methods compared in this study, the highest accuracy for individual steps was achieved with SFS (7 features) and Naive Bayes classifier (accuracy 75.3%), and the second highest accuracy with SFS (4 features) and k Nearest neighbours (accuracy 75.1%). Leave-one-subject-out cross-validation was used in the analysis. For the overall classification of each subject, which was based on the majority vote of the classified steps, k Nearest Neighbors provided the most accurate result with an accuracy of 84.5% and an error rate of 15.5%. This study shows the differences in feature selection methods and classifiers and provides generalizations for optimizing methodologies for smartphone-based monitoring of PD patients. The results are promising for further developing the analysis system for longer measurements carried out in free-living conditions.
  • Nordic Study Grp Pediat Rheumatolo; Nordal, Ellen; Rypdal, Veronika; Arnstad, Ellen Dalen; Aalto, Kristiina; Berntson, Lillemor; Ekelund, Maria; Peltoniemi, Suvi; Rygg, Marite (2019)
    BackgroundThe aim of the study was to describe school attendance and participation in physical education in school among children with juvenile idiopathic arthritis (JIA).MethodsConsecutive cases of JIA from defined geographical areas of Finland, Sweden and Norway with disease onset in 1997 to 2000 were followed for 8 years in a multi-center cohort study, aimed to be as close to population-based as possible. Clinical characteristics and information on school attendance and participation in physical education (PE) were registered.ResultsParticipation in school and in PE was lowest initially and increased during the disease course. Eight years after disease onset 228/274 (83.2%) of the children reported no school absence due to JIA, while 16.8% reported absence during the last 2 months due to JIA. Full participation in PE was reported by 194/242 (80.2%), partly by 16.9%, and none by 2.9%. Lowest participation in PE was found among children with ERA and the undifferentiated categories. Absence in school and PE was associated with higher disease activity measures at the 8-year visit. School absence >1day at baseline predicted use of disease-modifying anti-rheumatic drugs, including biologics (DMARDs) (OR 1.2 (1.1-1.5)), and non-remission off medication (OR 1.4 (1.1-1.7) 8 years after disease onset.ConclusionSchool absence at baseline predicted adverse long-term outcome. In children and adolescents with JIA participation in school activities is mostly high after 8years of disease. For the minority with low participation, special attention is warranted to promote their full potential of social interaction and improve long-term outcome.
  • Kuusalo, Laura; Puolakka, Kari; Kautiainen, Hannu; Karjalainen, Anna; Malmi, Timo; Yli-Kerttula, Timo; Leirisalo-Repo, Marjatta; Rantalaiho, Vappu; NEO-RACo Study Grp (2017)
    Identifying prognostic factors for remission in early rheumatoid arthritis (ERA) patients is of key clinical importance. We studied patient-reported outcomes (PROs) as predictors of remission in a clinical trial. We randomized 99 untreated ERA patients to receive remission-targeted treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months, and infliximab or placebo for the initial 6 months. At baseline, we measured following PROs: eight Short Form 36 questionnaire (SF-36) dimensions, patient's global assessment [PGA, visual analogue scale (VAS)], Health Assessment Questionnaire (HAQ), and pain VAS. We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years. Follow-up data at 2 years were available for 93 patients (92%), and 58 patients (62%) were in remission. At baseline, patients who achieved remission had higher radiological score (p = 0.04), lower tender joint count (p = 0.001), lower PGA (p = 0.005) and physician's global assessment (p = 0.019), lower HAQ (p = 0.016), less morning stiffness (p = 0.009), and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not. In multivariable models that included all PROs, remission was associated with SF-36 dimensions higher vitality (odds ratio 2.01; 95% confidence interval 1.19-3.39) and better emotional role functioning (odds ratio 1.64; 95% confidence interval 1.01-2.68). PGA, pain VAS, HAQ, and other SF-36 dimensions were not associated with remission. We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA.
  • Rypdal, Veronika; Arnstad, Ellen Dalen; Aalto, Kristiina; Berntson, Lillemor; Ekelund, Maria; Fasth, Anders; Glerup, Mia; Herlin, Troels; Nielsen, Susan; Peltoniemi, Suvi; Zak, Marek; Rygg, Marite; Rypdal, Martin; Nordal, Ellen (2018)
    Background: The aim was to develop prediction rules that may guide early treatment decisions based on baseline clinical predictors of long-term unfavorable outcome in juvenile idiopathic arthritis (JIA). Methods: In the Nordic JIA cohort, we assessed baseline disease characteristics as predictors of the following outcomes 8 years after disease onset. Non-achievement of remission off medication according to the preliminary Wallace criteria, functional disability assessed by Childhood Health Assessment Questionnaire (CHAQ) and Physical Summary Score (PhS) of the Child Health Questionnaire, and articular damage assessed by the Juvenile Arthritis Damage Index-Articular (JADI-A). Multivariable models were constructed, and cross-validations were performed by repeated partitioning of the cohort into training sets for developing prediction models and validation sets to test predictive ability. Results: The total cohort constituted 423 children. Remission status was available in 410 children: 244 (59.5%) of these did not achieve remission off medication at the final study visit. Functional disability was present in 111/340 (32.7%) children assessed by CHAQ and 40/199 (20.1%) by PhS, and joint damage was found in 29/216 (13.4%). Model performance was acceptable for making predictions of long-term outcome. In validation sets, the area under the curves (AUCs) in the receiver operating characteristic (ROC) curves were 0.78 (IQR 0.72-0.82) for non-achievement of remission off medication, 0.73 (IQR 0.67-0.76) for functional disability assessed by CHAQ, 0.74 (IQR 0.65-0.80) for functional disability assessed by PhS, and 0.73 (IQR 0.63-0.76) for joint damage using JADI-A. Conclusion: The feasibility of making long-term predictions of JIA outcome based on early clinical assessment is demonstrated. The prediction models have acceptable precision and require only readily available baseline variables. Further testing in other cohorts is warranted.
  • Koivunen, Sanna; Viljakainen, Matti; Männistö, Tuija; Gissler, Mika; Pouta, Anneli; Kaaja, Risto; Eriksson, Johan; Laivuori, Hannele; Kajantie, Eero; Vääräsmäki, Marja (2020)
    Objective To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. Design A retrospective cohort study. Setting Six secondary and tertiary delivery hospitals in Finland in 2009. Population Pregnant women (N = 4,033) and their offspring. Methods We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. Main outcome measures GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. Results Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring’s BWSDS and CS rate were higher than in controls. Conclusions GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia.
  • Rönö, Kristiina; Stach-Lempinen, Beata; Eriksson, Johan Gunnar; Pöyhönen-Alho, Maritta; Klemetti, Miira Marjuska; Roine, Risto Paavo; Huvinen, Emilia; Andersson, Sture; Laivuori, Hannele; Valkama, Anita; Meinilä, Jelena; Kautiainen, Hannu; Tiitinen, Aila; Koivusalo, Saila Birgitta (2018)
    Purpose: Lifestyle intervention studies performed during pregnancy have shown inconsistent results in relation to prevention of gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the effect of an intervention initiated already before pregnancy in prevention of GDM in high-risk women. Patients and methods: A randomized controlled trial was conducted in four Finnish maternity hospitals between the years 2008 and 2014. Altogether 228 high-risk women planning pregnancy were randomized to an intervention (n=116) or a control group (n=112). The risk factors were body mass index >= 30 kg/m(2) (n=46), prior GDM (n=120), or both (n=62), without manifest diabetes at study inclusion. Trained study nurses provided individualized lifestyle counseling every 3 months in addition to a group session with a dietician. The control group received standard antenatal care. GDM was defined as one or more pathological glucose values in a 75 g 2-hour oral glucose tolerance test, performed between 12 and 16 weeks of gestation and if normal repeated between 24 and 28 weeks of gestation. Results: Within 12 months, 67% of the women (n=72) in the intervention group and 63% of the women (n=71) in the control group (p=0.84) became pregnant. The cumulative incidence of GDM among the women available for the final analyses was 60% (n=39/65) in the intervention group and 54% (n=34/63) in the control group (p=0.49). GDM was diagnosed already before 20 weeks of gestation in 60% (n=44/73) of the cases. Conclusion: The preconceptional lifestyle intervention applied in the present study did not reduce the incidence of GDM.
  • Ekelund, Maria; Aalto, Kristiina; Fasth, Anders; Herlin, Troels; Nielsen, Susan; Nordal, Ellen; Peltoniemi, Suvi; Rygg, Marite; Zak, Marek; Berntson, Lillemor; Nordic Study Grp Pediat Rheumatol (2017)
    Background: To study the impact of psoriasis and features associated with psoriasis on classification and outcome in a population-based follow-up cohort of children with juvenile idiopathic arthritis (JIA). Methods: In all, 440 children with JIA were followed for a median of 8 years in a prospective Nordic population-based cohort study. Data for remission was available for 427 of these children. The presence of psoriasis, psoriasis-like rash, dactylitis, nail pitting, enthesitis, tenosynovitis and heredity was assessed in relation to ILAR classification and remission. Results: Clinical findings associated with psoriasis developed consecutively during the 8-year period. Six of 14 children with psoriasis were not classified as juvenile psoriatic arthritis according to the ILAR criteria at 8 year follow-up. Dactylitis was more common in children with early onset of JIA. After 8 years we found a cumulative median number of eleven arthritic joints in children with psoriasis or psoriasis- like rash compared with six in the rest of the cohort (p = 0.02). Also, the chance for not being in remission after 8 years increased significantly in patients with psoriasis, psoriasis-like rash or at least two of: 1) first-degree heredity for psoriasis or psoriatic arthritis, 2) dactylitis or 3) nail pitting, compared with the rest of the group (OR 3.32, p = 0.010). Conclusions: Our results indicate a more severe disease over time in psoriasis- associated JIA, as features of psoriasis develop during the disease course. This group is a major challenge to encompass in a future JIA classification in order to facilitate early tailored treatment.
  • Rosenstrom, Tom; Jokela, Markus (2017)
    Background: Diagnostic definitions for depressive disorders remain a debated topic, despite their central role in clinical practice and research. We use both recent evidence and nationally representative data to derive an empirically-based modification of DSM-IV/-5 Major Depressive Disorder (MDD). Method: A modified MDD diagnosis was derived by analyzing data from Collaborative Psychiatric Epidemiology Surveys, a multistage probability sample of adults (n=20 013; age >= 18 years) in coterminous USA, Alaska and Hawaii. The old and the newly suggested MDD definitions were compared for their associated disability (WHO Disability Assessment Schedule and number of disability days in past month), suicide attempt, and other covariates. Results: Our data-driven definition for major depression was "lack of interest to all or most things" plus four other symptoms from the set (weight gain, weight loss, insomnia, psychomotor retardation, fatigue, feelings of worthlessness, diminished ability to think concentrate, suicidal ideation attempt}. The new definition captured all the disability implied by MDD and excluded cases that showed no greater disability than the general population nor increased risk of suicide attempts. The lifetime prevalence of the new diagnosis was 14.7% (95% CI=14-15.4%) of the population, slightly less than for the old definition (16.4%; CI =15.4-17.3%). Limitations: Only conservative modifications of MDD could be studied, because of restrictions in the symptom data. Conclusions: With only small adjusting, the new definition for major depression may be more clinically relevant than the old one, and could serve as a conservative replacement for the old definition. (C) 2016 Elsevier B.V. All rights reserved.
  • Sivunen, Johanna; Karlberg, Susann; Lohi, Jouko; Karlberg, Niklas; Lipsanen-Nyman, Marita; Jalanko, Hannu (2017)
    Background Mulibrey nanism (MUL) is a rare inherited disease caused by genetic defects affecting peroxisomal TRIM37 protein. MUL affects multiple organs, leading to growth retardation and early onset type 2 diabetes. We aimed to characterize the structure and function of kidneys and the urinary tract in a large cohort of Finnish MUL patients. Methods Ultrasound, magnetic resonance imaging (MRI), and autopsy findings of the kidneys and urinary tract from 101 MUL patients were retrospectively analyzed. Renal function was examined using blood and urine biochemistry. Kidney pathology was assessed by histology and immunohistochemistry from biopsy and autopsy samples. Results Structural anomalies of the kidneys and urinary tract were found in 13 % of MUL patients and renal tumors and macroscopic cystic lesions in 14 % and 43 % respectively. Overall, kidney histology was well preserved, but glomerular cysts with a wide Bowman's space were observed in most samples (87 %). Also, prominent and abundant blood vessels with thick walls were typically seen. Expression of endothelial cell markers and angiogenic growth factors PDGF-B and FGF1 (but not VEGF-A) was significantly increased in MUL kidneys. Markers of fibrosis and epithelial-mesenchymal transformation, a-SMA, and vimentin were moderately up-regulated. Despite radiological and histological changes, most MUL patients (age 0.2-51 years) had normal kidney function. However, 9 out of 36 patients (25 %) had hypertension and 6 out of 26 (23 %) had mildly decreased glomerular filtration. Conclusions Genetic defects in the TRIM37 gene lead to an increased risk for kidney anomalies, renal tumors, and solitary cysts in addition to glomerular cystic lesions, but not to progressive deterioration of renal function.
  • Hammer, Hilde Berner; Hansen, Inger Marie Jensen; Järvinen, Pentti; Leirisalo-Repo, Marjatta; Ziegelasch, Michael; Agular, Birte; Terslev, Lene (2021)
    Objectives. Given that subjective variables might reduce remission by composite DAS (CDAS), the main objectives were to explore whether RA patients with mainly tender vs mainly swollen joints had differences in patient-reported outcome measures (PROMs), clinical or US assessments or in achieving remission defined by CDAS or US. Methods. In a Nordic multicentre study, RA patients initiating tocilizumab were assessed by PROMs, clinical, laboratory and US assessments (36 joints and 4 tendons) at baseline, 4, 12 and 24 weeks. Remission was defined according to clinical disease activity index (CDAI)/Boolean or no Doppler activity present. Tender-swollen joint differences (TSJDs) were calculated. Statistics exploring changes over time/differences between groups included Wilcoxon, Mann-Whitney, Kruskal-Wallis and Spearman tests. Results. One hundred and ten patients were included [mean (S.D.) age 55.6 (12.1) years, RA duration 8.7 (9.5) years]. All PROMs, clinical, laboratory and US scores decreased during follow-up (P < 0.001). During follow-up, tender joint counts were correlated primarily with PROMs [r = 0.24-0.56 (P < 0.05-0.001)] and swollen joint counts with US synovitis scores [r = 0.33-0.72 (P < 0.05-0.001)]. At 24 weeks, patients with TSJD > 0 had higher PROMs and CDAI (P < 0.05-0.001) but lower US synovitis scores (P < 0.05). Remission by CDAI/Boolean was seen in 26-34% and by Doppler 53%, but only 2-3% of patients with TSJD > 0 achieved CDAI/Boolean remission. Conclusion. Patients with more tender than swollen joints scored higher on subjective assessments but had less US synovitis. They seldom achieved CDAS remission despite many being in Doppler remission. If patients with predominantly tender joints do not reach CDAS remission, objective assessments of inflammation should be performed.
  • Liukkonen, Ville; Nordin, Arno; Arola, Johanna; Färkkilä, M; Åberg, F (2020)
    Abstract Background The etiology and prognosis of acute liver failure (ALF) remains unknown in a significant proportion of cases. Signs of autoimmunity may be present, but no consistent pattern has been observed. We aimed to analyse if pretransplant immunological findings, HLA haplotypes and clinical features among patients with unknown etiology differ from those of autoimmune or other known etiology. We also analysed whether such signs impact post-transplant biopsy findings or complications. Methods All adult ALF patients undergoing liver transplantation (LT) in Finland during 1987-2015 were followed to 2016. Data were from the LT registry, pathology database and patient records. 124 patients were included in the analysis. Study subgroups were acute autoimmune hepatitis (AIH) (n=25), known non-AIH etiology (n=54), and unknown etiology (n=45). Results The unknown etiology group differed from the known non-AIH group with regard to the following pretransplant autoimmunity-associated features: positive pANCA (35% vs 8%; P=0.02), higher mean IgA (3.2±1.7 vs 2.1±1.4, P=0.006) and IgG (12.7±4.3 vs 8.5±3.6, P=0.001). AIH-associated HLA haplotypes B8, DR3 and B8DR3 were more common in the AIH group (40%, 44% and 36%) and in the unknown group (29%, 33% and 29%) than in the known non-AIH group (11%, 17% and 11%) or in the Finnish general population (17%, 18% and 8%). However, these findings had no association with protocol biopsies, extrahepatic autoimmune diseases or survival. Patients with ≥1 rejection episode had higher pretransplant IgA (3.7±2.3 vs 2.6±1.2, P=0.02) and IgG (16.4±10.2 vs 12.4±6.8, P=0.03) than those without rejections. Conclusions Autoimmunity-associated pretransplant laboratory findings and HLA haplotypes were common in ALF of unknown etiology, but showed minimal predictive value for post-transplant biopsy findings, clinical complications or survival.
  • Laakasuo, Michael; Repo, Marko; Drosinou, Maria-Anna; Berg, Anton; Kunnari, Anton Johannes Olavi; Koverola, Mika; Saikkonen, Teemu Juhani; Hannikainen, Ivar; Visala, Aku; Sundvall, Jukka (2021)
    Mind upload, making a digital copy of one's brain, is a part of the transhumanistic dream of eternal life and the end of suffering. It is also perceived as a viable route toward artificial general intelligence (AGI). However, AI safety research has alerted to one major risk in creating AGI by mind upload: namely, that mind upload technology could appeal primarily to callous and selfish individuals who then abuse this technology for their personal gain'and, potentially, at a considerable cost to the welfare of humankind. Therefore, it is important to understand whether people's acceptance of mind upload is associated with pathological and/or antisocial traits. To this end, the present research examined whether individual differences in Dark Triad traits predict attitudes toward mind upload in a sample of 1007 English-speaking adults. A pre-registered structural equation model revealed that Machiavellianism (but not psychopathy) was associated with favorable views about mind upload, both directly and indirectly through utilitarian moral attitudes. These results therefore substantiate the concerns voiced by AI safety researchers'namely, that mind upload technology could be adopted disproportionately by individuals with an antisocial personality.
  • RAXO Study Grp; Uutela, A.; Ovissi, A.; Hakkarainen, A.; Ristimäki, A.; Lundbom, N.; Kallio, R.; Soveri, L. M.; Salminen, T.; Algars, A.; Halonen, P.; Ristamaki, R.; Nordin, A.; Sequeiros, R. Blanco; Rinta-Kiikka, I.; Lantto, E.; Virtanen, J.; Paakko, E.; Liukkonen, E.; Saunavaara, J.; Ryymin, P.; Lammentausta, E.; Osterlund, P.; Isoniemi, H. (2021)
    Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.
  • Kaltiala-Heino, Riittakerttu; Sumia, Maria; Tyolajarvi, Marja; Lindberg, Nina (2015)
    Background: Increasing numbers of adolescents present in adolescent gender identity services, desiring sex reassignment (SR). The aim of this study is to describe the adolescent applicants for legal and medical sex reassignment during the first two years of adolescent gender identity team in Finland, in terms of sociodemographic, psychiatric and gender identity related factors and adolescent development. Methods: Structured quantitative retrospective chart review and qualitative analysis of case files of all adolescent SR applicants who entered the assessment by the end of 2013. Results: The number of referrals exceeded expectations in light of epidemiological knowledge. Natal girls were markedly overrepresented among applicants. Severe psychopathology preceding onset of gender dysphoria was common. Autism spectrum problems were very common. Conclusion: The findings do not fit the commonly accepted image of a gender dysphoric minor. Treatment guidelines need to consider gender dysphoria in minors in the context of severe psychopathology and developmental difficulties.
  • Selenius, Jannica S.; Martelius, Timi; Pikkarainen, Sampsa; Siitonen, Sanna; Mattila, Eero; Pietikainen, Risto; Suomalainen, Pekka; Aalto, Arja H.; Saarela, Janna; Einarsdottir, Elisabet; Jarvinen, Asko; Farkkila, Martti; Kere, Juha; Seppanen, Mikko (2017)
    Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia and impaired vaccine response. Aim: To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland. Methods: We performed a cross-sectional study to assess all adult CVID patients followed up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax (R) were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 mu g/mL after vaccination. We further characterized the patients' B cell phenotypes and complications associated with CVID. Results: In total, 9 patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID." Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow-up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow-up was seen in as many as 16% of "Xprobable CVID" patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication. Conclusion: The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.
  • ReACCh-Out NoSPeR Investigators; Rypdal, Veronika (2019)
    Background: Models to predict disease course and long-term outcome based on clinical characteristics at disease onset may guide early treatment strategies in juvenile idiopathic arthritis (JIA). Before a prediction model can be recommended for use in clinical practice, it needs to be validated in a different cohort than the one used for building the model. The aim of the current study was to validate the predictive performance of the Canadian prediction model developed by Guzman et al. and the Nordic model derived from Rypdal et al. to predict severe disease course and non-achievement of remission in Nordic patients with JIA. Methods: The Canadian and Nordic multivariable logistic regression models were evaluated in the Nordic JIA cohort for prediction of non-achievement of remission, and the data-driven outcome denoted severe disease course. A total of 440 patients in the Nordic cohort with a baseline visit and an 8-year visit were included. The Canadian prediction model was first externally validated exactly as published. Both the Nordic and Canadian models were subsequently evaluated with repeated fine-tuning of model coefficients in training sets and testing in disjoint validation sets. The predictive performances of the models were assessed with receiver operating characteristic curves and C-indices. A model with a C-index above 0.7 was considered useful for clinical prediction. Results: The Canadian prediction model had excellent predictive ability and was comparable in performance to the Nordic model in predicting severe disease course in the Nordic JIA cohort. The Canadian model yielded a C-index of 0.85 (IQR 0.83-0.87) for prediction of severe disease course and a C-index of 0.66 (0.63-0.68) for prediction of non-achievement of remission when applied directly. The median C-indices after fine-tuning were 0.85 (0.80-0.89) and 0.69 (0.65-0.73), respectively. Internal validation of the Nordic model for prediction of severe disease course resulted in a median C-index of 0.90 (0.86-0.92). Conclusions: External validation of the Canadian model and internal validation of the Nordic model with severe disease course as outcome confirm their predictive abilities. Our findings suggest that predicting long-term remission is more challenging than predicting severe disease course.
  • Bong, Indah Waty; Moeliono, Moira; Wong, Grace Yee; Brockhaus, Maria (2019)
    Despite the growing interest in social forestry, how much do we understand the social, economic and environmental outcomes and the conditions that enable SF to perform? In this article, we use a content analysis of literature on existing traditional SF practiced throughout Indonesia. It examines the outcomes of these systems and the conditions that enabled or hindered these outcomes to understand possible causal relations and changing dynamics between these conditions and SF performance. We discuss the gaps in how SF is assessed and understood in the literature to understand the important aspects of traditional SF that are not captured or that are lost when the diverse traditional systems are converted into other land uses. It aims to understand the potential trade-offs in the State’s push for formalizing SF if these aspects continue to be ignored.