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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.

Artificial intelligence based methods, especially machine learning (ML), are increasingly used in healthcare for automatic medical image analysis and clinical decision support systems. Development and validation of ML models involve processing of large volumes of personal data. We analysed regulatory impacts on ML based application development especially from the perspective of privacy protection and usage of ML models as a basis for software under medical device regulation (MDR). We present best practices for ML application development and personal data usage in a use case of predicting elderly individuals’ future need for healthcare and social welfare services. publishedVersion

Publisher Copyright: © 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics 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.

Anna-Leena Vuorinen,1 Mika Lehto,2,3 Mikko Niemi,4,5 Kari Harno,6 Juha Pajula,1 Mark van Gils,1 Jaakko Lähteenmäki7 1VTT Technical Research Centre of Finland, Tampere, Finland; 2Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland; 3University of Helsinki, Helsinki, Finland; 4Department of Clinical Pharmacology and Individualized Drug Therapy Research Program, University of Helsinki, Helsinki, Finland; 5Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland; 6Department of Health and Social Management, University of Eastern Finland, Kuopio, Finland; 7VTT Technical Research Centre of Finland, Espoo, FinlandCorrespondence: Anna-Leena VuorinenVTT Technical Research Centre of Finland, P.O. Box 1300, Tampere, 33101, FinlandTel +358 40 8485966Email anna-leena.vuorinen@vtt.fiPurpose: 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.Keywords: pharmacogenomics, warfarin, bleeding, INR, CYP2C9, VKORC1

Precision medicine is fueled by data and biosample collections produced in healthcare settings. Efficient exploitation of these data requires investments in setting up the infrastructures for secondary use of data and in supporting related R&D activities. This paper presents an ecosystem model for evaluating the impact of public investments on the business activities of companies and the resulting societal and economic benefits.

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

DECIPHER is a pre-commercial procurement (PCP) project seeking mHealth solutions for cross border health services. The 4phase PCP process is meant to be a tool for procurers to develop together with SMEs solutions to their specific needs. SMEs may have excellent solutions as well as the flexibility and adoptability to react adequately to procurers needs. But with little access to competitions, information about their solutions is not always reaching procurers …

eHealth studies typically suffer from high attrition rates. Objective To investigate type 2 diabetes and heart disease patients’ adherence to a self-management intervention that combined health coaching and telemonitoring. Methods Renewing Health Finland was a 12-month randomized controlled trial to improve quality of life (QoL) and/or HbA1c of 595 patients with chronic conditions. The intervention consisted of (1) weekly measurement of health parameters (2) health coaching every 4–6 weeks. Adherence to telemonitoring was defined as the percentage of weeks with at least one reported health measurement. Adherence to coaching was defined as the number of received calls. Results The median percentage of monitored weeks was 65 % without time-dependent attrition. 66 % of participants received 7–11 calls that corresponds to the predefined coaching schedule. Adherence did not correlate with QoL or HbA1c. Discussion Our results indicate that the intervention in the Renewing Health Finland trial was delivered almost with planned intensity.

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.

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 phones—of 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’ comorbidities—40% (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 life—heart 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). [J Med Internet Res 2015;17(6):e153]

DECIPHER (European Commission FP7 co-funded project) procures the research and development of novel solutions for secure cross-border access to personal health records and efficient and safe medical care for mobile patients with chronic diseases or unplanned care episodes. Interoperability and privacy challenges of cross-border care are tackled. Understanding of the Pre- Commercial Procurement (PCP) instrument and new knowledge for improving future European PCPs is obtained. Key aspects, such as the business case formulation, promote new concepts for procuring authorities and their operations. Following needs assessment, market consultations, a call for bids and evaluation, lessons learned as seen by the participating experts, are: The need of the procurers and the adequacy of the solution to the existing service system should be assessed in advance.

International audience; Data collected by multiple physiological sensors are being increasingly used for wellness monitoring or disease management, within a pervasiveness context facilitated by the massive use of mobile devices. These abundant complementary raw data are challenging to understand and process, because of their voluminous and heterogeneous nature, as well as the data quality issues that could impede their utilization. This chapter examines the main data quality questions concerning six frequently used physiological sensors - glucometer, scale, blood pressure me-ter, heart rate meter, pedometer, and thermometer -, as well as patient observations that may be associated to a given set of measurements. We discuss specific details that are either overlooked in the literature or avoided by data exploration and information extraction algorithms, but have significant importance to properly pre-process these data. Making use of different types of formalized knowledge, according to the characteristics of physiological measurement devices, relevant data handled by a Personal Health Record on a mobile device, are evaluated from a data quality perspective, considering data deficiencies factors, consequences and reasons. We propose a general scheme for sensors data quality characterization adapted to a pervasive scenario.

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.

Summary Objectives: There is an increasing need for userfriendly and interoperable mobile applications in health and wellness domain. The objective of this work has been to provide support for rapid and cost-effective development of such applications. Methods: We have introduced an application framework which provides a generic tool for mobile application designers. We have demonstrated the usage of the application framework by providing an example implementation and demonstrating its usage in a Tele-ECG use case. In order to support interoperability we propose a solution compatible with clinical document standards such as the HL7 CDA. Results: A new mobile platform applicable for a wide range of telemedicine and wellness applications is introduced. The platform provides connectivity between healthcare professionals, patients and measurement devices. It is based on an open application framework that provides interfaces for measurement, user interface, database and network connectivity implementations. Conclusions: Mobile application development based on the application framework was demonstrated successfully. The developed UPHIAC platform adopts a new technical approach using a local database solution for caching of information at the mobile terminal. The platform applies a document-based approach providing a versatile and reliable way of sharing and collabora - tively complementing of health information including standard information model documents (HL7/CDA), and integration with health information systems and personal storages. The implemented mobile tele-ECG case demonstrates the overall function of the platform. The platform can be used as a basis for developing new applications for specific purposes.

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.

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 well being 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.

Location-Aided Planning (LAP) technique provides possibility to use mobile phone measurements for monitoring network performance and traffic conditions. It enables detection of problem areas in the network, creation of alternative network plans for various traffic conditions as well as tuning and validation of propagation models with measurement data retrieved from the network. The paper reports results of a trial validating the LAP concept performed in standard GSM 1800 network in the frame of the EU IST project Cellular Network Optimization Based on Mobile Location (CELLO) [1]. During the trial, the accuracy of four selected location methods was evaluated. The measurements done during the trial were additionally used for assessment of the propagation model based on the well-known Okumura–Hata model with some corrections due to diffraction, building and land cover effects.

The paper presents fast two-dimensional (2-D) diffraction modelling in the horizontal plane for site-specific propagation prediction in urban micro-cellular environments. Comparison with measurements and simulation of published results validate the 2-D modelling that significantly reduces the computation time and overcomes the limitation and difficulty of existing techniques for multiple building diffraction. The modelling makes three contributions which are 1) extension of an expression for multiple building forward diffraction and use of the extended formulation, 2) equivalent source technique for parallel-street multiple diffraction and 3) inclusion of reflections from curved surfaces of street building corners. Additional comparisons of three-dimensional model prediction with measurements for an urban line-of-sight environment place the work in a more complete context The results show that an increase in the number of rays may not enhance the accuracy of ray-tracing model prediction.

The new work makes three UTD (uniforn geometrical theory of diffraction) based path-loss prediction models and their experimental validations for urban micro-cellular mobile radio communications. The three models apply to the base station and mobile antennas much lower than the surrounding buildings and can be written in explicit forms for both vertical-and horizontal-polarization transmission and reception. Comparisons of their predictions with measurements at 900.5 and 1800 MHz in shadow zones of urban areas confirm the three models experimentally. The results demonstrate that fast two-dimensional (2-D) models which do not require a building height database can provide acceptable accuracy for micro-cellular mobile radio propagation predictions in urban environments. The methodology of this work is to deternine in advance significant rays to use, from a particular geometry of the buildings in an urban area. It appears suitable here for 2-D modeling for parallel-street problem and irregular side-street problems. It has the potential to be used in practical design of micro-cellular mobile radio systems.

Radiowave propagation measurements at 1.7 GHz for indoor mobile systems are described. A coherent pulse measurement is used to measure path loss and complex power delay profile of the radio channel. The results show that path loss and delay spread are highly dependent on building architecture and materials. By introducing special attenuation factors for penetrated walls and floors a statistical path loss model is obtained which gives relatively good results in office environments with small rooms. For large rooms and open areas a conventional model with distance dependence works best. Delay spread is modelled by having the volume of the indoor environment as a model parameter.

Remote patient monitoring systems provide plenty of structured information about the monitored health variables. We propose a set of parameters that exploits the remotely monitored data to describe patient's monitoring adherence from different viewpoints. The parameters were applied in self-monitored weight and blood pressure data sets of 30 heart failure patients inherited from a clinical trial setting. With the help of the extracted adherence parameters the thirty heart failure patients were clustered into two subgroups with different monitoring profiles: a group of well-performing subjects (n=22) and a group of low-performing subjects (n=8). Beneficial effects of active monitoring were reflected as positive changes in clinical health outcomes and lowered burdening of health care providers among the group of well-performing subjects.

Telemedicine is gaining popularity due to its high potential for cost savings and increased efficiency in healthcare delivery. However, most telemedicine systems available in the markets are limited to particular applications and lack interoperability with other information systems and measurement devices. In this paper, we present a generic service platform, which is applicable in a wide range of telemedicine applications and in other areas involving the need for confidential information exchange. The platform particularly addresses the security challenges in the case when the information technology (IT) is outsourced to an external company. It also provides semantic interoperability by providing support to HL7 CDA R2 documents. The platform implementation, the PIR document service, is composed of software components for the health service provider, the IT service provider and the telemedicine customers. These include desktop, mobile and browser-based applications. The platform was tested in a tele-consultation trial where the Heart Centre of Pirkanmaa Hospital District offered cardiology consultation service for two remote health care units. The outcome of the test was positive. Both the Heart Centre cardiologists and the physicians of the remote units considered the benefits of the consultation service to be high. The consultation cases included refining cardiology diagnostics and medication as well as guidance for patient logistics. The physicians considered it feasible to use a commercial consultation service when available.

Biobanking and secondary use of healthcare data enable considerable improvement to healthcare through personalized medicine including innovative therapies, pharmaceuticals, medical technology, and healthcare processes tailored for the needs of individuals. The data-driven precision medicine ecosystem requires contributions from a large variety of stakeholders as well as public investments to boost ecosystem growth. This paper introduces a system dynamics model describing mechanisms for biobank data and biosample accumulation and the related impact to pharmaceutical R&D projects. The preliminary simulation results reflect the important role of public funding of the infrastructure needed for biobank and register data exploitation as well as setting up services to attract more donors. Large public-private precision medicine projects, such as the FinnGen project are in a key role. Further work is needed to improve the ecosystem model precision especially in taking into account the differences between pharmaceutical R&D projects and their data exploitation needs.