Generating Synthetic Longitudinal Patient Data with the PrivBayes Method

In this thesis, the PrivBayes method is used to generate synthetic longitudinal patient data and the quality of the generated data is evaluated. In addition, this thesis briefly discusses the current situation of processing health data in Finland and proposes a simplistic definition of synthetic tabular data as well as presents different methods to evaluate the utility of generated synthetic data. The PrivBayes method is based on approximating the association structure of a data set using a Bayesian network and generating synthetic data from the conditional distributions corresponding to the structure of the network. The method ensures the privacy of the data by applying differential privacy through the addition of noise in the data generation process in a specific way. The method is applied to data collected from the database of Auria Clinical Informatics under permission number T152/2017. The data set consists of 2890 individual patients diagnosed with either type 1 or type 2 diabetes and seven different characteristics collected for each patient: age, body mass index, complications related to diabetes, gender, type of diabetes and two measurements for glycated hemoglobin that represent the repeated measurements in the data. The PrivBayes method is evaluated by generating 27 different synthetic data sets, describing the structures of the Bayesian network of each data set and visually inspecting differences between the original data and each synthetic data set. Differences between data sets are considered in terms of similarity of univariate distributions, differences in Pearson’s sample correlation coefficients and sample Cramer’s V coefficients and the results of a linear mixed-effects model. In conclusion, the PrivBayes method failed to produce synthetic longitudinal patient data of sufficient quality to be applicable as such in practice. However, this thesis revealed some shortcomings of the method and potential targets for further research and development.Tässä pro gradu -tutkielmassa käytetään PrivBayes-menetelmää synteettisen potilasseuranta- aineiston tuottamiseksi ja arvioidaan tuotetun aineiston laatua. Tämän lisäksi tutkielmassa kerrotaan lyhyesti terveystietojen käsittelyn nykytilanteesta Suomessa, minkä lisäksi ehdotetaan yksinkertaista määritelmää synteettiselle taulukkomuotoiselle aineistolle sekä esitellään menetelmiä tuotetun synteettisen aineiston käytettävyyden arvioimiseksi. PrivBayes-menetelmä perustuu aineistossa esiintyvien assosiaatiorakenteiden mallintamiseen Bayes-verkon avulla ja synteettisen aineiston tuottamiseen ehdollisista jakaumista, jotka vastaavat verkon rakennetta. Menetelmä varmistaa aineiston tietosuojan soveltamalla differentiaalista yksityisyyttä, jossa aineiston tuotantoprosessiin lisätään tietyn tyyppistä kohinaa. Menetelmää sovelletaan aineistoon, joka on kerätty Auria Tietopalveluiden tietokannasta tietolupanumerolla T152/2017. Aineisto koostuu 2890 yksittäisestä potilaasta, joilla on diagnosoitu joko tyypin 1 tai 2 diabetes, ja seitsemästä eri potilaita kuvaavasta muuttujasta: iästä, painoindeksistä, diabetekseen liittyvistä komplikaatiosta, sukupuolesta, diabeteksen tyypistä sekä kahdesta glykatoituneen hemoglobiinin mittauksesta, jotka edustavat seurantamittauksia aineistossa. PrivBayes-menetelmää arvioidaan luomalla 27 erilaista synteettistä aineistoa, kuvailemalla kutakin aineistoa vastaava Bayes-verkon rakenne sekä arvioimalla visuaalisesti alkuperäisen aineiston ja synteettisen aineiston välisiä eroja yksiulotteisissa jakaumissa, Pearsonin otoskorrelaatio- ja Cramerin V-kertoimissa sekä lineaarisen sekamallin tuloksissa. Tutkielman johtopäätöksenä voidaan todeta, että PrivBayes-menetelmä ei kyennyt tuottamaan riittävän laadukasta synteettistä potilasseuranta-aineistoa, jota voitaisiin sellaisenaan soveltaa käytännössä. Tutkielma kuitenkin paljasti joitakin menetelmän puutteita sekä mahdollisia kohteita jatkotutkimukselle ja -kehitykselle

Methods for generating and evaluating synthetic longitudinal patient data: a systematic review

The proliferation of data in recent years has led to the advancement and utilization of various statistical and deep learning techniques, thus expediting research and development activities. However, not all industries have benefited equally from the surge in data availability, partly due to legal restrictions on data usage and privacy regulations, such as in medicine. To address this issue, various statistical disclosure and privacy-preserving methods have been proposed, including the use of synthetic data generation. Synthetic data are generated based on some existing data, with the aim of replicating them as closely as possible and acting as a proxy for real sensitive data. This paper presents a systematic review of methods for generating and evaluating synthetic longitudinal patient data, a prevalent data type in medicine. The review adheres to the PRISMA guidelines and covers literature from five databases until the end of 2022. The paper describes 17 methods, ranging from traditional simulation techniques to modern deep learning methods. The collected information includes, but is not limited to, method type, source code availability, and approaches used to assess resemblance, utility, and privacy. Furthermore, the paper discusses practical guidelines and key considerations for developing synthetic longitudinal data generation methods

General practitioners' self-reported competence in the management of sexual health issues - a web-based questionnaire study from Finland

Objective Although sexual problems are common, they are rarely brought up in appointments with general practitioners (GPs). We aimed to assess the barriers that hinder GPs from bringing up sexual health issues and to evaluate the need for education on sexual medicine. Design A web-based questionnaire was used. Setting Four fields were included: A) the self-reported competence in discussing sexual health and treating patients with these issues, B) the barriers to bringing up patients' sexual health problems, C) the source of education on sexual medicine and D) the need for education on sexual medicine. Subjects A random sample of 1000 GPs in Finland (a response rate of 43.5%, n = 402). Main outcome measures GPs' self-assessed competence in discussing and treating sexual health issues, related barriers to bringing up the topic and the reported need for education. Results The main reasons reported for not bringing up sexual health issues were shortness of the appointment time (85.6%), a lack of knowledge (83.6%) and a lack of experience with sexual medicine (81.8%). The male GPs reported better competence in discussing the issues and treating male patients, whereas the female GPs reported better competence in discussing the issues with female patients. No differences emerged between genders regarding treating female patients. Nearly 90% of the GPs expressed needing more education about sexual medicine. Conclusions Although the GPs reported good competence in discussing sexual health issues with their patients, several barriers to bringing up sexual health issues emerged. Continuing education was desired and could lessen these barriers.</p

Characterization of real-world treatment practices and outcomes among patients with chronic lymphocytic leukemia treated in a Finnish tertiary center

ObjectivesWe conducted this retrospective study to characterize the change in chronic lymphocytic leukemia (CLL) treatment patterns between 2005 and 2019, to understand the treatment sequencing across the course of the disease, and to investigate how targeted agents and prognostic testing were implemented into the patient care.MethodsThis study included adult patients with CLL treated at the Hospital District of Southwest Finland during the study period. Data were collected from the Turku University Hospital data lake.ResultsIn total, 122 and 60 patients received first- and second-line treatments for CLL, respectively. The shift from conventional chemoimmunotherapy to targeted treatments in recent years (2014–2019) was observed. The median overall survival times were not reached in patients treated with targeted agents compared to conventional standard treatments in first- and second-line settings and improved toward the end of the study period. Prognostic testing increased during the study follow-up and patients with unmutated immunoglobulin heavy-chain variable showed significantly poorer overall survival and time-to-next-treatment outcomes than patients with mutated immunoglobulin heavy-chain variable.ConclusionsThis real-world study implicated added value of targeted chemo-free therapies as reported in randomized clinical trials, and highlighted the necessity of prognostic testing in order to improve treatment selection and patient outcomes.</p

Complications and reoperations related to tension band wiring and plate osteosynthesis of olecranon fractures

BackgroundOlecranon fractures are common and usually treated operatively either by tension band wiring (TBW) or plate fixation (PF). The aim of this study was to assess early complications and reoperations and their predictive factors related to those operative methods.MethodsA retrospective analysis of all patients with an operatively treated olecranon fracture between 2007 and 2017 at Turku University hospital was performed. Reoperations, postoperative complications, and potential risk factors for these were recorded.ResultsA total of 434 patients (387 TBW and 47 PF) were identified. There was no statistically significant difference in the rate of early complications (49% vs. 62%, P = .262) or reoperations (38% vs. 53%, P = .079) between patients treated with TBW and PF. In the TBW group, the intramedullary placement of Kirschner (K)-wires predisposed patients to complications compared to transcortical placement of the K-wires according to multivariate analysis (odds ratio [OR] 1.94, P = .026). Younger age was associated with the frequency of reoperations, the odds decreasing 24% for every 10 years of age (P P = .002). Also, excellent postoperative reduction was associated with higher reoperation rate than good or fair reduction (OR 0.48, P = .033).ConclusionThere is a high risk of early complications and reoperations associated to both TBW and PF. Transcortical positioning of K-wires may reduce the rate of complications in TBW.Level of EvidenceLevel III; Retrospective Cohort Comparison; Treatment Study</p

Randomized controlled trial comparing pit crew resuscitation model against standard advanced life support training

Objectives Pit crew models are designed to improve teamwork in critical medical situations, like advanced life support (ALS). We investigated if a pit crew model training improves performance assessment and ALS skills retention when compared to standard ALS education. Methods This was a prospective, blinded, randomized, and controlled, parallel-group trial. We recruited students to 4-person resuscitation teams. We video recorded simulated ALS-situations after the ALS education and after 6-month follow-up. We analyzed technical skills (TS) and non-technical skills (NTS) demonstrated in them with an instrument measuring TS and NTS, and used a linear mixed model to model the difference between the groups in the TS and NTS. Another linear model was used to explore the difference between the groups in hands-on ratio and hands-free time. The difference in the total assessment score was analyzed with the Mann-Whitney U-test. The primary outcome was the difference in the total assessment score between the groups at follow-up. ALS skills were considered to be a secondary outcome. Results Twenty-six teams underwent randomization. Twenty-two teams received the allocated education. Fifteen teams were evaluated at 6-month follow-up: 7 in the intervention group and 8 in the control group. At 6-month follow-up, the median (Q(1)-Q(3)) total assessment score for the control group was 6.5 (6-8) and 7 (6.25-8) for the intervention group but the difference was not significant (U = 133, P = 0.373). The intervention group performed better in terms of chest compression quality (interaction term, beta 3 = 0.23; 95% confidence interval, 0.01-0.50; P = 0.043) at follow-up. Conclusion We found no difference in overall performance between the study arms. However, trends indicate that the pit crew model may help to retain ALS skills in different areas like chest compression quality.</p

An observational study of technical and non-technical skills in advanced life support in the clinical setting

ObjectiveTechnical skills (TS) and non-technical skills (NTS) are the primary elements ensuring patient safety during advanced life support (ALS) and effective crisis resource management (CRM). Both skills are needed to perform high-quality ALS, though they are traditionally practiced separately. The evidence of the association between NTS and TS in high-quality ALS performance is insufficient. Hence, we aimed to evaluate the association between the skills in real-life in-hospital ALS situations.MethodsWe video recorded real-life in-hospital ALS situations, analyzed TS and NTS demonstrated in them with an instrument measuring TS and NTS, and tested the linear association between NTS and TS using a linear mixed model.ResultsAmong 50 real-life in-hospital ALS situations that we recorded, 20 had adequate data for analysis. NTS and TS total scores were associated with one another (slope 0.48, P P chest compression quality, ventilation quality, rhythm control and defibrillation quality) were associated with one another (slopes ranging from 0.37 to 0.56, P ConclusionsThe resuscitation teams who demonstrated good NTS also performed the technical aspects of ALS better. The results suggest that NTS and TS have an association with one another in real-life in-hospital ALS situations. NTS performance had the most evident association with chest compression quality and rhythm control and defibrillation quality; these are considered the most crucial elements affecting outcomes of ALS. The findings of the study present novel information of what and why to emphasize in ALS training.Clinical trial registration. ClinicalTrials.gov, NCT03017144.</p

Clinical Characteristics and Disease Course of Fibrosing Interstitial Lung Disease Patients in a Real-World Setting

Background and Objectives: This single-center retrospective study was conducted to describe clinical characteristics and the disease course of patients with interstitial lung diseases (ILD). Materials and Methods: The study included adult patients with fibrosing ILD (IPF, non-IPF fibrosing ILD (F-ILD), and non-IPF progressive pulmonary fibrosis (PPF)) treated between 2014 and 2017. Patients were followed annually from the first visit until the end of the study period in 2019. Data were collected from the Turku University Hospital data lake and analyzed using descriptive statistics. Results: 591 patients formed the patient cohort: 110 had IPF, 194 F-ILD, 142 PPF, and the remaining 145 patients were uncertain, F-ILD-U, whose disease progression nature could not be confirmed by FVC measurements. There were more males in each patient group and median age of the groups was similar, although there were younger patients in the PPF, F-ILD, and F-ILD-U groups. PPF patients had more patterns of UIP than F-ILD patients. Exposure-related ILDs were clearly the most found ILD diagnoses for both PPF and F-ILD, followed by unclassifiable IIP. Baseline predicted FVC % reduction in every group was moderate. Half of the patients in each group had comorbidities, and the most common were cardiovascular diseases, diabetes, sleep apnea, and chronic lower respiratory diseases; F-ILD-U patients had malignant diseases as well. IPF patients had less medications than the other groups. Glucocorticoids were the most used medication in all patient groups. More PPF and F-ILD patients remained in the follow-up than IPF and F-ILD-U patients. Similarly, mortality of F-ILD-U was the highest, followed by IPF. Evolvement of lung function, oxygen use, and number of acute hospitalizations were similar for IPF and PPF patients whereas the corresponding results were always better for F-ILD patients. Conclusions: The disease course of IPF and PPF was similar, and PPF patient amount exceeded the amount of IPF patients

Clinical Characteristics and Disease Course of Fibrosing Interstitial Lung Disease Patients in a Real-World Setting

Background and Objectives: This single-center retrospective study was conducted to describe clinical characteristics and the disease course of patients with interstitial lung diseases (ILD). Materials and Methods: The study included adult patients with fibrosing ILD (IPF, non-IPF fibrosing ILD (F-ILD), and non-IPF progressive pulmonary fibrosis (PPF)) treated between 2014 and 2017. Patients were followed annually from the first visit until the end of the study period in 2019. Data were collected from the Turku University Hospital data lake and analyzed using descriptive statistics. Results: 591 patients formed the patient cohort: 110 had IPF, 194 F-ILD, 142 PPF, and the remaining 145 patients were uncertain, F-ILD-U, whose disease progression nature could not be confirmed by FVC measurements. There were more males in each patient group and median age of the groups was similar, although there were younger patients in the PPF, F-ILD, and F-ILD-U groups. PPF patients had more UIP pattern than F-ILD patients. Exposure-related ILDs were clearly the most found ILD diagnoses for both PPF and F-ILD, followed by unclassifiable IIP. Baseline FVC % predicted reduction in every group was moderate. Half of the patients in each group had comorbidities, and the most common were cardiovascular diseases, diabetes, sleep apnea, and chronic lower respiratory diseases; F-ILD-U patients had malignant diseases as well. IPF patients had less medications than the other groups. Glucocorticoids were the most used medication in all patient groups. More PPF and F-ILD patients remained in the follow-up than IPF and F-ILD-U patients. Similarly, mortality of F-ILD-U was the highest, followed by IPF. Evolvement of lung function, oxygen use, and number of acute hospitalizations were similar for IPF and PPF patients whereas the corresponding results were always better for F-ILD patients. Conclusions: The disease course of IPF and PPF was similar, and PPF patient amount exceeded the amount of IPF patients

Characterization of real‐world treatment practices and outcomes among patients with chronic lymphocytic leukemia treated in a Finnish tertiary center

Abstract Objectives We conducted this retrospective study to characterize the change in chronic lymphocytic leukemia (CLL) treatment patterns between 2005 and 2019, to understand the treatment sequencing across the course of the disease, and to investigate how targeted agents and prognostic testing were implemented into the patient care. Methods This study included adult patients with CLL treated at the Hospital District of Southwest Finland during the study period. Data were collected from the Turku University Hospital data lake. Results In total, 122 and 60 patients received first‐ and second‐line treatments for CLL, respectively. The shift from conventional chemoimmunotherapy to targeted treatments in recent years (2014–2019) was observed. The median overall survival times were not reached in patients treated with targeted agents compared to conventional standard treatments in first‐ and second‐line settings and improved toward the end of the study period. Prognostic testing increased during the study follow‐up and patients with unmutated immunoglobulin heavy‐chain variable showed significantly poorer overall survival and time‐to‐next‐treatment outcomes than patients with mutated immunoglobulin heavy‐chain variable. Conclusions This real‐world study implicated added value of targeted chemo‐free therapies as reported in randomized clinical trials, and highlighted the necessity of prognostic testing in order to improve treatment selection and patient outcomes