TWINGEN - protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer's disease.

Introduction: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among Finnish biobank donors according to TWINGEN study criteria. Methods and analysis: A multi-center study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behavior and sleep. A sub-cohort are being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. TWINGEN data will be transferred to Finnish Institute of Health and Welfare (THL) biobank and we aim to further to transfer it to the FinnGen study where it will be combined with health registry data for prediction of AD. Ethics and dissemination: This recall study consists of FTC/THL/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Pharmacogenetics of warfarin and healthcare costs - Real-world data analysis.

PURPOSE: Variants in CYP2C9 and VKORC1 genes have been associated with individuals' sensitivity to warfarin. The aim of this study was to investigate the differences of healthcare costs of genetically normal and genetically sensitive warfarin responder groups. METHODS: This was a retrospective study linking genotype data from three Finnish biobanks (THL Biobank, Auria Biobank, Helsinki Biobank) with healthcare encounter data of the Finnish Institute of Health and Welfare (THL), drug dispensation data from the Social Insurance Institution of Finland (Kela) and laboratory data from Finnish hospital districts and municipalities. We compared the normal and sensitive warfarin responder groups in terms of healthcare costs related to bleeding and thromboembolic events, INR tests and medication purchases. RESULTS: We found a trend towards increased bleeding-related hospital costs in the sensitive warfarin responder group (881 patients) when compared with the normal responders (1627 patients) with a per patient difference of 150.9 €/year (95% CI: -55.1, 414.6 €/year, p = 0.087). INR test costs were higher in the sensitive responder group with a difference of 7.2 €/year (95% CI: -1.5, 16.4 €/year, p = 0.047). Medication costs were significantly lower in the sensitive responder group with a difference of -14.4 €/year (95% CI: -15.8, -12.9 €/year, p < 0.001). CONCLUSIONS: The difference in the costs of bleeding-related hospitalization between genetically sensitive and normal warfarin responders may justify genotype-guided warfarin dosing. Further studies with larger sample sizes would be needed to verify the result.

Integrating data from multiple Finnish biobanks and national health-care registers for retrospective studies: Practical experiences.

Aim: This case study aimed to investigate the process of integrating resources of multiple biobanks and health-care registers, especially addressing data permit application, time schedules, co-operation of stakeholders, data exchange and data quality. Methods: We investigated the process in the context of a retrospective study: Pharmacogenomics of antithrombotic drugs (PreMed study). The study involved linking the genotype data of three Finnish biobanks (Auria Biobank, Helsinki Biobank and THL Biobank) with register data on medicine dispensations, health-care encounters and laboratory results. Results: We managed to collect a cohort of 7005 genotyped individuals, thereby achieving the statistical power requirements of the study. The data collection process took 16 months, exceeding our original estimate by seven months. The main delays were caused by the congested data permit approval service to access national register data on health-care encounters. Comparison of hospital data lakes and national registers revealed differences, especially concerning medication data. Genetic variant frequencies were in line with earlier data reported for the European population. The yearly number of international normalised ratio (INR) tests showed stable behaviour over time. Conclusions: A large cohort, consisting of versatile individual-level phenotype and genotype data, can be constructed by integrating data from several biobanks and health data registers in Finland. Co-operation with biobanks is straightforward. However, long time periods need to be reserved when biobank resources are linked with national register data. There is a need for efforts to define general, harmonised co-operation practices and data exchange methods for enabling efficient collection of data from multiple sources.

Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users.

This study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single-nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18-0.98, P = 0.044) and 1236T-2677T-3435T (rs1128503-rs2032582-rs1045642) haplotype (HR 0.44, 95% CI, 0.20-0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C-2677G-3435C (HR 2.55, 95% CI, 1.03-6.36, P = 0.044) and 1236T-2677G-3435C (HR 5.88, 95% CI, 2.35-14.72, P < 0.001) haplotypes with an increased risk for thromboembolic outcomes in rivaroxaban users. The ABCB1 c.2482-2236G>A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16-0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.

Pharmacogenetics of Anticoagulation and Clinical Events in Warfarin-Treated Patients: A Register-Based Cohort Study with Biobank Data and National Health Registries in Finland.

PURPOSE: To assess the association between VKORC1 and CYP2C9 variants and the incidence of adverse drug reactions in warfarin-treated patients in a real-world setting. MATERIALS AND METHODS: This was a register-based cohort study (PreMed) linking data from Finnish biobanks, national health registries and patient records between January 1st 2007 and June 30th 2018. The inclusion criteria were: 1) ≥18 years of age, 2) CYP2C9 and VKORC1 genotype information available, 3) a diagnosis of a cardiovascular disease, 4) at least one warfarin purchase, 5) regular INR tests. Eligible individuals were divided into two warfarin sensitivity groups; normal responders, and sensitive and highly sensitive responders based on their VKORC1 and CYP2C9 genotypes. The incidences of clinical events were compared between the groups using Cox regression models. RESULTS: The cohort consisted of 2508 participants (45% women, mean age of 69 years), of whom 65% were categorized as normal responders and 35% sensitive or highly sensitive responders. Compared to normal responders, sensitive and highly sensitive responders had fewer INR tests below 2 (median: 33.3% vs 43.8%, 95% CI: -13.3%, -10.0%) and more above 3 (median: 18.2% vs 6.7%, 95% Cl: 8.3%, 10.8%). The incidence (per 100 patient-years) of bleeding outcomes was 5.4 for normal responders and 5.6 for the sensitive and highly sensitive responder group (HR=1.03, 95% CI: 0.74, 1.44). The incidence of thromboembolic outcomes was 4.9 and 7.8, respectively (HR=1.48, 95% CI: 1.08, 2.03). CONCLUSION: In a real-world setting, genetically sensitive and highly sensitive responders to warfarin had more high INR tests and required a lower daily dose of warfarin than normal responders. However, the risk for bleeding events was not increased in sensitive and highly sensitive responders. Interestingly, the risk of thromboembolic outcomes was lower in normal responders compared to the sensitive and highly sensitive responders. TRIAL REGISTRATION: NCT04001166.

Telemonitoring and Mobile Phone-Based Health Coaching Among Finnish Diabetic and Heart Disease Patients: Randomized Controlled Trial.

BACKGROUND: There is a strong will and need to find alternative models of health care delivery driven by the ever-increasing burden of chronic diseases. OBJECTIVE: The purpose of this 1-year trial was to study whether a structured mobile phone-based health coaching program, which was supported by a remote monitoring system, could be used to improve the health-related quality of life (HRQL) and/or the clinical measures of type 2 diabetes and heart disease patients. METHODS: A randomized controlled trial was conducted among type 2 diabetes patients and heart disease patients of the South Karelia Social and Health Care District. Patients were recruited by sending invitations to randomly selected patients using the electronic health records system. Health coaches called patients every 4 to 6 weeks and patients were encouraged to self-monitor their weight, blood pressure, blood glucose (diabetics), and steps (heart disease patients) once per week. The primary outcome was HRQL measured by the Short Form (36) Health Survey (SF-36) and glycosylated hemoglobin (HbA1c) among diabetic patients. The clinical measures assessed were blood pressure, weight, waist circumference, and lipid levels. RESULTS: A total of 267 heart patients and 250 diabetes patients started in the trial, of which 246 and 225 patients concluded the end-point assessments, respectively. Withdrawal from the study was associated with the patients' unfamiliarity with mobile phones­of the 41 dropouts, 85% (11/13) of the heart disease patients and 88% (14/16) of the diabetes patients were familiar with mobile phones, whereas the corresponding percentages were 97.1% (231/238) and 98.6% (208/211), respectively, among the rest of the patients (P=.02 and P=.004). Withdrawal was also associated with heart disease patients' comorbidities­40% (8/20) of the dropouts had at least one comorbidity, whereas the corresponding percentage was 18.9% (47/249) among the rest of the patients (P=.02). The intervention showed no statistically significant benefits over the current practice with regard to health-related quality of life­heart disease patients: beta=0.730 (P=.36) for the physical component score and beta=-0.608 (P=.62) for the mental component score; diabetes patients: beta=0.875 (P=.85) for the physical component score and beta=-0.770 (P=.52) for the mental component score. There was a significant difference in waist circumference in the type 2 diabetes group (beta=-1.711, P=.01). There were no differences in any other outcome variables. CONCLUSIONS: A health coaching program supported with telemonitoring did not improve heart disease patients' or diabetes patients' quality of life or their clinical condition. There were indications that the intervention had a differential effect on heart patients and diabetes patients. Diabetes patients may be more prone to benefit from this kind of intervention. This should not be neglected when developing new ways for self-management of chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT01310491; http://clinicaltrials.gov/ct2/show/NCT01310491 (Archived by WebCite at http://www.webcitation.org/6Z8l5FwAM).

Use of home telemonitoring to support multidisciplinary care of heart failure patients in Finland: randomized controlled trial.

BACKGROUND: Heart failure (HF) patients suffer from frequent and repeated hospitalizations, causing a substantial economic burden on society. Hospitalizations can be reduced considerably by better compliance with self-care. Home telemonitoring has the potential to boost patients' compliance with self-care, although the results are still contradictory. OBJECTIVE: A randomized controlled trial was conducted in order to study whether the multidisciplinary care of heart failure patients promoted with telemonitoring leads to decreased HF-related hospitalization. METHODS: HF patients were eligible whose left ventricular ejection fraction was lower than 35%, NYHA functional class ≥2, and who needed regular follow-up. Patients in the telemonitoring group (n=47) measured their body weight, blood pressure, and pulse and answered symptom-related questions on a weekly basis, reporting their values to the heart failure nurse using a mobile phone app. The heart failure nurse followed the status of patients weekly and if necessary contacted the patient. The primary outcome was the number of HF-related hospital days. Control patients (n=47) received multidisciplinary treatment according to standard practices. Patients' clinical status, use of health care resources, adherence, and user experience from the patients' and the health care professionals' perspective were studied. RESULTS: Adherence, calculated as a proportion of weekly submitted self-measurements, was close to 90%. No difference was found in the number of HF-related hospital days (incidence rate ratio [IRR]=0.812, P=.351), which was the primary outcome. The intervention group used more health care resources: they paid an increased number of visits to the nurse (IRR=1.73, P<.001), spent more time at the nurse reception (mean difference of 48.7 minutes, P<.001), and there was a greater number of telephone contacts between the nurse and intervention patients (IRR=3.82, P<.001 for nurse-induced contacts and IRR=1.63, P=.049 for patient-induced contacts). There were no statistically significant differences in patients' clinical health status or in their self-care behavior. The technology received excellent feedback from the patient and professional side with a high adherence rate throughout the study. CONCLUSIONS: Home telemonitoring did not reduce the number of patients' HF-related hospital days and did not improve the patients' clinical condition. Patients in the telemonitoring group contacted the Cardiology Outpatient Clinic more frequently, and on this way increased the use of health care resources. TRIAL REGISTRATION: Clinicaltrials.gov NCT01759368; http://clinicaltrials.gov/show/NCT01759368 (Archived by WebCite at http://www.webcitation.org/6UFxiCk8Z).

Active assistance technology reduces glycosylated hemoglobin and weight in individuals with type 2 diabetes: results of a theory-based randomized trial.

BACKGROUND: Type 2 diabetes is an individual health challenge requiring ongoing self-management. Remote patient reporting of relevant health parameters and linked automated feedback via mobile telephone have potential to strengthen self-management and improve outcomes. This research involved development and evaluation of a mobile telephone-based remote patient reporting and automated telephone feedback system, guided by health behavior change theory, aimed at improving self-management and health status in individuals with type 2 diabetes. SUBJECTS AND METHODS: This research comprised a randomized controlled trial. Inclusion criteria were diagnosis of type 2 diabetes, elevated glycosylated hemoglobin (HbA1c) levels (range, 6.5-11%) or use of oral diabetes medication, and 30-70 years of age. Intervention subjects (n=24) participated in remote patient reporting of health status parameters and linked health behavior change feedback. Control participants (n=24) received standard of care including diabetes education and healthcare provider counseling. Patients were followed for approximately 10 months. RESULTS: Intervention participants achieved, compared with controls and controlling for baseline, a significantly greater mean reduction in HbA1c of -0.40% (95% confidence interval [CI] -0.67% to -0.14%) versus 0.036% (95% CI -0.23% to 0.30%) (P<0.03) and significantly greater weight reduction of -2.1 kg (95% CI -3.6 to -0.6 kg) versus 0.4 kg (95% CI -1.1 to 1.9 kg). Nonsignificant trends for greater intervention compared with control improvement in systolic and diastolic blood pressure were observed. CONCLUSIONS: Sophisticated information technology platforms for remote patient reporting linked with theory-based health behavior change automated feedback have potential to improve patient outcomes in type 2 diabetes and merit scaled-up research efforts.

Interoperability of personal health records.

Personal Health Records (PHR's) and related services are emerging rapidly. Currently, most PHR's are isolated and do not communicate with other systems. Standards for interoperability exist, but they are oriented towards clinical applications. However, a substantial part of a typical PHR consists of non-clinical information such as a health diary. The present paper highlights the requirements related to exchanging non-clinical PHR information between services and shows how this information exchange can be accomplished. The approach utilizes a SOAP message for carrying the actual PHR content in a structure referred as Health Diary Entry (HDE) document. The HDE document provides mechanisms to bind the contents to external vocabularies and ontologies to achieve semantic interoperability. The approach was successfully tested in the context of an occupational health pilot, in which data contents from several health and wellness applications were merged into a common database.

The role of continuous monitoring in a 24/7 telecardiology consultation service--a feasibility study.

Today's coronary care unit patients include those with complicated and uncomplicated myocardial infarction, decompensated heart failure and frank cardiogenic shock, severe valvular heart disease, high-grade conduction disturbances, and incessant ventricular arrhythmias. Increasingly in modern medicine, these conditions are not seen in isolation but rather in connection with a series of additional medical comorbidities. Increased life expectancy results in an increase in the prevalence of chronic cardiovascular diseases and an increased demand for health care services. Telemedicine is the provision of health care services, through the use of information and communication technology, in situations where the health care professional and the patient, or 2 health care professionals, are not in the same location. It involves the secure transmission of medical data and information, through text, sound, images, or other forms needed for the prevention, diagnosis, treatment, and follow-up of a patient. Telecardiology is one of the oldest applications in telemedicine and has been largely applied during the last 10 to 20 years. This study evaluated the feasibility of remote surveillance of coronary care unit and cardiology ward patient monitoring data by a "telecardiologist" with access to electronic health care record data and digitally stored 12-lead electrocardiograms. The remote access to the hospital intranet proved to be technically feasible. Also, the server applications used over the remote connection proved to be reliable and showed robustness against network performance variations. Extending remote patient surveillance to other hospitals is possible, provided that similar electrocardiogram and electronic health care record applications are available and a remote access can be arranged to them. However, the usability from cardiologist's perspective may be degraded if connecting with multiple applications and hospital networks is needed. The study indicated potential for speeding up the diagnostic and therapeutic processes in the hospital, although the study was limited in that the telecardiologist played a passive role and did not acutely impact patient care. In the future, the system could be expanded to surveillance of smaller hospitals. Telemedicine has the potential to aid in solving the conflict between aging of population, rise in the demand for critical care services, and shortage of professional personnel. This might, however, require a more active remote surveillance than the one tested in this study. Privacy- and security-related aspects are major components of building trust and confidence in telemedicine systems. In telecardiology, the real-time interactive telemedicine model with 24/7 service has potential superior performance compared with a store-and-forward telemedicine model.

A service platform architecture design towards a light integration of heterogeneous systems in the wellbeing domain.

System integration is one of the major challenges for building wellbeing or healthcare related information systems. In this paper, we are going to share our experiences on how to design a service platform called Nuadu service platform, for providing integrated services in occupational health promotion and health risk management through two heterogeneous systems. Our design aims for a light integration covering the layers, from data through service up to presentation, while maintaining the integrity of the underlying systems.

A concept for ICT assisted health promotion in the occupational healthcare.

Lifestyle related health risks, such as overweight, work stress, and physical inactivity, have become pervasive in most modern societies. These risk factors have a debilitating impact on the wellbeing of citizens and play a major role in the onset of many chronic diseases. As a result, working life is affected due to impaired work ability, decreased productivity, absenteeism, and disability pensions. Lifestyle changes are the key to managing these problems, but they are often difficult to accomplish and maintain. We present a concept for ICT (Information and Communication Technology) assisted health promotion in the occupational healthcare. ICT tools are provided for employees participating in a face-to-face intervention, which is designed to address several health risks. We believe that through ICT, we can provide the employees with more personalized health management support more efficiently than before. The ICT system will be implemented by integrating different technologies into an interoperable system.

Ontology-based approach for managing personal health and wellness information.

This paper describes a new approach for collecting and sharing personal health and wellness information. The approach is based on a Personal Health Record (PHR) including both clinical and non-clinical data. The PHR is located on a network server referred as Common Server. The overall service architecture for providing anonymous and private access to the PHR is described. Semantic interoperability is based on an ontology collection and usage of OID (Object Identifier) codes. The formal (upper) ontology combines a set of domain ontologies representing different aspects of personal health and wellness. The ontology collection emphasizes wellness aspects while clinical data is modelled by using OID references to existing vocabularies. Modular ontology approach enables distributed management and expansion of the data model.