Browsing by Subject "Survival analysis"

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  • Ryynanen, Olli-Pekka; Soini, Erkki J.; Lindqvist, Ari; Kilpelainen, Maritta; Laitinen, Tarja (2013)
    Background: Chronic obstructive pulmonary disease (COPD) is associated with increased mortality and poor health-related quality of life (HRQoL) compared with the general population. The objective of this study was to identify clinical characteristics which predict mortality and very poor HRQoL among the COPD population and to develop a Bayesian prediction model. Methods: The data consisted of 738 patients with COPD who had visited the Pulmonary Clinic of the Helsinki and Turku University Hospitals during 1995-2006. The data set contained 49 potential predictor variables and two outcome variables: survival (dead/alive) and HRQoL measured with a 15D instrument (very poor HRQoL <0.70 vs. typical HRQoL >= 0.70). In the first phase of model validation we randomly divided the material into a training set (n = 538), and a test set (n = 200). This procedure was repeated ten times in random fashion to obtain independently created training sets and corresponding test sets. Modeling was performed by using the training set, and each model was tested by using the corresponding test set, repeated in each training set. In the second phase the final model was created by using the total material and eighteen most predictive variables. The performance of six logistic regressions approaches were shown for comparison purposes. Results: In the final model, the following variables were associated with mortality or very poor HRQoL: age at onset, cerebrovascular disease, diabetes, alcohol abuse, cancer, psychiatric disease, body mass index, Forced Expiratory Volume (FEV1) % of predicted, atrial fibrillation, and prolonged QT time in ECG. The prediction accuracy of the model was 77%, sensitivity 0.30, specificity 0.95, positive predictive value 0.68, negative predictive value 0.78, and area under the ROC curve 0.69. While the sensitivity of the model reminded limited, good specificity, moderate accuracy, comparable or better performance in classification and better performance in variable selection and data usage in comparison to the logistic regression approaches, and positive and negative predictive values indicate that the model has potential in predicting mortality and very poor HRQoL in COPD patients. Conclusion: We developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD.
  • Koivusaari, Katariina; Syrjälä, Essi; Niinistö, Sari; Takkinen, Hanna-Mari; Ahonen, Suvi; Åkerlund, Mari; Korhonen, Tuuli E.; Toppari, Jorma; Ilonen, Jorma; Peltonen, Jaakko; Nevalainen, Jaakko; Knip, Mikael; Alatossava, Tapani; Veijola, Riitta; Virtanen, Suvi M (2020)
    Several prospective studies have shown an association between cows’ milk consumption and the risk of islet autoimmunity and/or type 1 diabetes. We wanted to study whether processing of milk plays a role. A population-based birth cohort of 6081 children with HLA-DQB1-conferred risk to type 1 diabetes was followed until the age of 15 years. We included 5545 children in the analyses. Food records were completed at the ages of 3 and 6 months and 1, 2, 3, 4 and 6 years, and diabetes-associated autoantibodies were measured at 3–12-month intervals. For milk products in the food composition database, we used conventional and processing-based classifications. We analysed the data using a joint model for longitudinal and time-to-event data. By the age of 6 years, islet autoimmunity developed in 246 children. Consumption of all cows’ milk products together (energy-adjusted hazard ratio 1·06; 95 % CI 1·02, 1·11; P = 0·003), non-fermented milk products (1·06; 95 % CI 1·01, 1·10; P = 0·011) and fermented milk products (1·35; 95 % CI 1·10, 1·67; P = 0·005) was associated with an increased risk of islet autoimmunity. The early milk consumption was not associated with the risk beyond 6 years. We observed no clear differences based on milk homogenisation and heat treatment. Our results are consistent with the previous studies, which indicate that high milk consumption may cause islet autoimmunity in children at increased genetic risk. The study did not identify any specific type of milk processing that would clearly stand out as a sole risk factor apart from other milk products.
  • Heikkinen, Ilkka (Helsingin yliopisto, 2018)
    Johdanto: : Sekuriini on proteiini, jolla on tärkeä merkitys solujen jakautumisessa. Sen pääasiallinen tehtävä on estää mitoosin aikana sisarkromatidien ennenaikainen irtoaminen toisistaan ennen kuin tumasukkulan muodostuminen on valmis. Sekuriini säätelee myös M-faasiin siirtymistä ja p53 proteiinin toimintaa, sekä osallistuu DNA:n korjausprosessiin. Sekuriinilla on todettu olevan merkittävä rooli myös useiden syöpien kehittymisessä. Tässä tutkimuksessa analysoimme sekuriinin tuotannon yhteyttä liikkuvan kielen levyepiteelikarsinoomapotilaiden ennusteeseen. Menetelmät: Tutkimusaineisto koostui 93 kielisyöpäpotilaasta, joiden diagnoosi sekä hoito toteutettiin Helsingin yliopistollisessa keskussairaalassa sekä Oulun yliopistollisessa sairaalassa vuosina 1981-2005. Sekuriinituotannon määrää ja sijaintia syöpäkudoksessa tutkittiin immunohistokemiallisesti siten, että 52 potilaan tissue microarray (TMA) ja 41 potilaan kasvainresekaattien histologiset leikkeet värjättiin monoklonaalisella sekuriini vasta-aineella. Sekuriinin määrää arvioitiin prosentuaalisena osuutena positiivisesti sekuriinivasta-aineella värjäytyneistä syöpäsoluista suhteessa kaikkiin kentässä näkyviin syöpäsoluihin. Tilastollisista analyyseistä khiin neliö -testiä käytettiin eri muuttujien välisten riippuvuuksien vertailussa. Kaplan-Meier kuvaajaa, log-rank testiä ja Coxin suhteellisen vaaran mallia sovellettiin elinaika-analyysissä. Tilastolliset analyysit tehtiin IBM SPSS (versio 20.0) tilastoanalyysiohjelmistolla. Tulokset: Sekuriinin yliekspressio liittyi merkittävästi syövän erilaistumisasteeseen (P=0.03). Sekuriinia oli enemmän levinneisyysasteeltaan pidemmälle edenneissä syövissä (asteet III ja IV), mutta tämä yhteys ei ollut tilastollisesti merkitsevä. Assosiaatiota ei myöskään löytynyt sekuriinin määrän ja kielisyöpäkuolleisuuden tai kielisyövän uusiutumisen välillä (P > 0.05). Johtopäätökset: Löydöksemme viittaavat siihen, että sekuriinin yliekspressiolla saattaa olla merkitystä kielisyövän etenemisessä, mutta sekuriini ei ennusta kielisyöpäpotilaan kuolleisuutta tautiin tai taudin uusiutumistaipumusta.
  • Ding, Yiyang; Leppälammi-Kujansuu, Jaana; Helmisaari, Heljä-Sisko (2019)
    Abstract 1. Fine root turnover plays a critical role in carbon and nutrient cycling in forest ecosystems. In this study, we focused on the most abundant deciduous species in Nordic countries, silver birch (Betula pendula Roth) and its fine root dynamics, including the amount of litter produced by fine roots as well as by aboveground vegetation. 2. The minirhizotron method was used to quantify fine root longevity of silver birch and understory fine roots and rhizomes in northern Finland. Fine root biomass per basal area and ectomycorrhizal short root numbers per mg were also quantified. The fine root litter production was estimated by fine root biomass and longevity, and then compared with the aboveground litter collected with litter traps. 3. Birch fine root biomass was 1.4-fold higher than that of understory fine roots and rhizomes (234 ± 22, 171 ± 19 g m−2 respectively). Fine root longevity of birch (372 days) was significantly (P < 0.05) shorter than that of understory vegetation (643 days). The birch fine root longevity was positively related to root diameter and soil depth. Hazard analysis showed that thicker roots, long roots, roots produced late in the growing season, and roots growing deeper in the soil had relatively lower mortality hazard compared to the reference data. The total annual soil C input, including both birch and understory, was 283 g C m−2 yr−1. The proportion of understory annual C input was 35% of the total. Total annual belowground C input was 1.4-fold greater than that of aboveground. 4. Our study indicated that the total annual belowground litter production was greater than that of the aboveground litter in a boreal deciduous forest stand. Therefore, more emphasis should be put to quantify the C cycling of both above- and belowground parts of different tree species as well as understory in boreal forests.
  • Chakroborty, Deepankar; Emani, Maheswara R; Klén, Riku; Böckelman, Camilla; Hagström, Jaana; Haglund, Caj; Ristimäki, Ari; Lahesmaa, Riitta; Elo, Laura L (BioMed Central, 2019)
    Abstract Background Prognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Methods Gene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N = 1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlation analysis was performed to investigate the role of the interactome of L1TD1 in colon cancer patients. Results We found L1TD1 as a novel positive prognostic marker for colon cancer. Increased expression of L1TD1 associated with longer disease-free survival in all the three data sets. Our results were in contrast to a previous study on medulloblastoma, where high expression of L1TD1 was linked with poor prognosis. Notably, in medulloblastoma L1TD1 was co-expressed with its interaction partners, whereas our analysis revealed lack of co-expression of L1TD1 with its interaction partners in colon cancer. Conclusions Our results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients.
  • Chakroborty, Deepankar; Emani, Maheswara Reddy; Klen, Riku; Bockelman, Camilla; Hagström, Jaana; Haglund, Caj; Ristimäki, Ari; Lahesmaa, Riitta; Elo, Laura L. (2019)
    BackgroundPrognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities.MethodsGene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N=1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlation analysis was performed to investigate the role of the interactome of L1TD1 in colon cancer patients.ResultsWe found L1TD1 as a novel positive prognostic marker for colon cancer. Increased expression of L1TD1 associated with longer disease-free survival in all the three data sets. Our results were in contrast to a previous study on medulloblastoma, where high expression of L1TD1 was linked with poor prognosis. Notably, in medulloblastoma L1TD1 was co-expressed with its interaction partners, whereas our analysis revealed lack of co-expression of L1TD1 with its interaction partners in colon cancer.ConclusionsOur results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients.
  • Baum, Ulrike; Kulathinal, Sangita; Auranen, Kari (2021)
    Background: Non-sensitive and non-specific observation of outcomes in time-to-event data affects event counts as well as the risk sets, thus, biasing the estimation of hazard ratios. We investigate how imperfect observation of incident events affects the estimation of vaccine effectiveness based on hazard ratios. Methods: Imperfect time-to-event data contain two classes of events: a portion of the true events of interest; and false-positive events mistakenly recorded as events of interest. We develop an estimation method utilising a weighted partial likelihood and probabilistic deletion of false-positive events and assuming the sensitivity and the false-positive rate are known. The performance of the method is evaluated using simulated and Finnish register data. Results: The novel method enables unbiased semiparametric estimation of hazard ratios from imperfect time-to-event data. False-positive rates that are small can be approximated to be zero without inducing bias. The method is robust to misspecification of the sensitivity as long as the ratio of the sensitivity in the vaccinated and the unvaccinated is specified correctly and the cumulative risk of the true event is small. Conclusions: The weighted partial likelihood can be used to adjust for outcome measurement errors in the estimation of hazard ratios and effectiveness but requires specifying the sensitivity and the false-positive rate. In absence of exact information about these parameters, the method works as a tool for assessing the potential magnitude of bias given a range of likely parameter values.
  • Baum, Ulrike; Kulathinal, Sangita; Auranen, Kari (BioMed Central, 2021)
    Abstract Background Non-sensitive and non-specific observation of outcomes in time-to-event data affects event counts as well as the risk sets, thus, biasing the estimation of hazard ratios. We investigate how imperfect observation of incident events affects the estimation of vaccine effectiveness based on hazard ratios. Methods Imperfect time-to-event data contain two classes of events: a portion of the true events of interest; and false-positive events mistakenly recorded as events of interest. We develop an estimation method utilising a weighted partial likelihood and probabilistic deletion of false-positive events and assuming the sensitivity and the false-positive rate are known. The performance of the method is evaluated using simulated and Finnish register data. Results The novel method enables unbiased semiparametric estimation of hazard ratios from imperfect time-to-event data. False-positive rates that are small can be approximated to be zero without inducing bias. The method is robust to misspecification of the sensitivity as long as the ratio of the sensitivity in the vaccinated and the unvaccinated is specified correctly and the cumulative risk of the true event is small. Conclusions The weighted partial likelihood can be used to adjust for outcome measurement errors in the estimation of hazard ratios and effectiveness but requires specifying the sensitivity and the false-positive rate. In absence of exact information about these parameters, the method works as a tool for assessing the potential magnitude of bias given a range of likely parameter values.
  • Vento, Seija I.; Jouhi, Lauri; Mohamed, Hesham; Haglund, Caj; Mäkitie, Antti A.; Atula, Timo; Hagström, Jaana; Mäkinen, Laura K. (2018)
    The objective of this study was to determine if matrix metalloproteinase-7 (MMP-7) expression is related to human papilloma virus (HPV) status, clinical parameters, and outcome in oropharyngeal squamous cell carcinoma (OPSCC). Tumor tissue specimens from 201 OPSCC patients treated with curative intent were available for immunohistochemistry, and the samples were stained with monoclonal MMP-7 antibody. All the patients were followed up at least 3 years or until death. MMP-7 expression did not differ between HPV-positive and HPV-negative patients. MMP-7 was not prognostic among patients with HPV-negative OPSCC. In the HPV-positive subgroup, patients with moderate, high, or very high MMP-7 expression had significantly worse 5-year disease-specific survival (DSS) (56.6%) than patients with absent, or low MMP-7 expression (77.2%), and MMP-7 expression appeared as a prognostic factor in the multivariate analysis. In addition, among HPV-positive OPSCC with moderate, high, or very high MMP-7 expression, the 5-year distant recurrence-free survival was significantly lower (69.6%) than in those who had low or absent MMP-7 expression (97.5%). Our results suggest that among HPV-positive OPSCC patients, high MMP-7 expression is related to worse 5-year DSS and increased rate of distant recurrences.