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.

The role of self-monitoring of blood glucose in patients treated with SGLT-2 inhibitors: a European expert recommendation.

The role for the novel treatment approach of sodium-glucose cotransporter-2 (SGLT-2) in type 2 diabetes is increasing. Structured self-monitoring of blood glucose (SMBG), based on a less intensive and a more intensive scheme, may contribute to an optimization of SGLT-2 inhibitor based treatment. The current expert recommendation suggests individualized approaches of SMBG, using simple and clinically applicable schemes. Potential benefits of SMBG in SGLT-2 inhibitor based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and education. The length and frequency of SMBG should depend on the clinical setting and the quality of metabolic control.

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.

Self-monitoring of blood glucose in type 2 diabetes: recent studies.

The increasing role for structured and personalized self-monitoring of blood glucose (SMBG) in management of type 2 diabetes has been underlined by randomized and prospective clinical trials. These include Structured Testing Program (or STeP), St. Carlos, Role of Self-Monitoring of Blood Glucose and Intensive Education in Patients with Type 2 Diabetes Not Receiving Insulin, and Retrolective Study Self-Monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (or ROSSO)-in-praxi follow-up. The evidence for the benefit of SMBG both in insulin-treated and non-insulin-treated patients with diabetes is also supported by published reviews, meta-analyses, and guidelines. A Cochrane review reported an overall effect of SMBG on glycemic control up to 6 months after initiation, which was considered to subside after 12 months. Particularly, the 12-month analysis has been criticized for the inclusion of a small number of studies and the conclusions drawn. The aim of this article is to review key publications on SMBG and also to put them into perspective with regard to results of the Cochrane review and current aspects of diabetes management.

Diabetes as a case study of chronic disease management with a personalized approach: the role of a structured feedback loop.

As non-communicable or chronic diseases are a growing threat to human health and economic growth, political stakeholders are aiming to identify options for improved response to the challenges of prevention and management of non-communicable diseases. This paper is intended to contribute ideas on personalized chronic disease management which are based on experience with one major chronic disease, namely diabetes mellitus. Diabetes provides a pertinent case of chronic disease management with a particular focus on patient self-management. Despite advances in diabetes therapy, many people with diabetes still fail to achieve treatment targets thus remaining at risk of complications. Personalizing the management of diabetes according to the patient's individual profile can help in improving therapy adherence and treatment outcomes. This paper suggests using a six-step cycle for personalized diabetes (self-)management and collaborative use of structured blood glucose data. E-health solutions can be used to improve process efficiencies and allow remote access. Decision support tools and algorithms can help doctors in making therapeutic decisions based on individual patient profiles. Available evidence about the effectiveness of the cycle's constituting elements justifies expectations that the diabetes management cycle as a whole can generate medical and economic benefit.

The role of self-monitoring of blood glucose in glucagon-like peptide-1-based treatment approaches: a European expert recommendation.

The role of glucagon-like peptide (GLP)-1-based treatment approaches for type 2 diabetes mellitus (T2DM) is increasing. Although self-monitoring of blood glucose (SMBG) has been performed in numerous studies on GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, the potential role of SMBG in GLP-1-based treatment strategies has not been elaborated. The expert recommendation suggests individualized SMBG strategies in GLP-1-based treatment approaches and suggests simple and clinically applicable SMBG schemes. Potential benefits of SMBG in GLP-1-based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and diabetes education. Its length and frequency should depend on the clinical setting and the quality of metabolic control. It is considered to play an important role for the optimization of diabetes management in T2DM patients treated with GLP-1-based approaches.

Health coaching by telephony to support self-care in chronic diseases: clinical outcomes from The TERVA randomized controlled trial.

BACKGROUND: The aim was to evaluate the effect of a 12-month individualized health coaching intervention by telephony on clinical outcomes. METHODS: An open-label cluster-randomized parallel groups trial. Pre- and post-intervention anthropometric and blood pressure measurements by trained nurses, laboratory measures from electronic medical records (EMR). A total of 2594 patients filling inclusion criteria (age 45 years or older, with type 2 diabetes, coronary artery disease or congestive heart failure, and unmet treatment goals) were identified from EMRs, and 1535 patients (59%) gave consent and were randomized into intervention or control arm. Final analysis included 1221 (80%) participants with data on primary end-points both at entry and at end. Primary outcomes were systolic and diastolic blood pressure, serum total and LDL cholesterol concentration, waist circumference for all patients, glycated hemoglobin (HbA1c) for diabetics and NYHA class in patients with congestive heart failure. The target effect was defined as a 10-percentage point increase in the proportion of patients reaching the treatment goal in the intervention arm. RESULTS: The proportion of patients with diastolic blood pressure initially above the target level decreasing to 85 mmHg or lower was 48% in the intervention arm and 37% in the control arm (difference 10.8%, 95% confidence interval 1.5-19.7%). No significant differences emerged between the arms in the other primary end-points. However, the target levels of systolic blood pressure and waist circumference were reached non-significantly more frequently in the intervention arm. CONCLUSIONS: Individualized health coaching by telephony, as implemented in the trial was unable to achieve majority of the disease management clinical measures. To provide substantial benefits, interventions may need to be more intensive, target specific sub-groups, and/or to be fully integrated into local health care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00552903.

Addressing schemes of self-monitoring of blood glucose in type 2 diabetes: a European perspective and expert recommendation.

Self-monitoring of blood glucose (SMBG) in type 2 diabetes has increasingly been shown to display beneficial effects on glycemic control. SMBG is not only associated with a reduction of hemoglobin A1c but has also been demonstrated to increase patients' awareness of the disease. SMBG has also the potential to visualize and predict hypoglycemic episodes. International guidelines by the International Diabetes Federation, the European Society of Cardiology, and the European Association for the Study of Diabetes and also the International Society for Pediatric and Adolescent Diabetes emphasize that SMBG is an integral part of self-management. More recently, two European consensus documents have been published to give recommendations for frequency and timing of SMBG also for various clinical scenarios. Recently, a European expert panel was held to further facilitate and enhance standardized approaches to SMBG. The aim was to present simple, clinically meaningful, and standardized SMBG strategies for type 2 diabetes. The panel recommended a less intensive and an intensive scheme for SMBG across the type 2 diabetes continuum. The length and frequency of SMBG performance depend on the clinical circumstances and the quality of glycemic control. The expert panel also recommended further evaluation of various schemes for SMBG in type 2 diabetes in clinical studies.

Sharable EHR systems in Finland.

In Finland, the shared record is a virtual electronic health record (EHR). It consists of health data generated, maintained and preserved by different health care service providers. Two different kinds of technologies for integrating regional EHR-systems are applied, but mainly by using a common middleware. Services provided by this middleware are EHR location services using a link repository and combining EHR-viewing services with security management services including consent management and identification services for health professionals. The Regional Health Information Organization (UUMA) approach is based on a stepwise implementation of integrated regional healthcare services to create a virtually borderless healthcare organization--a patient centered virtual workspace. In the virtual workspace multi-professional teams and patients collaborate and share information regardless of time and place. Presently the regional health information network (RHIN) is comprised of three integrated services between primary, secondary and tertiary care within the county of Uusimaa. The regional healthcare modules consist of an (1) eReferral network, (2) integrated EHR service between health care professionals and (3) PACS system. The eReferral between primary and secondary care not only speeds up the transfer, but also offers an option for communication in the form of eConsultation between general practitioners and hospital specialists. By sharing information and knowledge remote eConsultations create a new working environment for integrated delivery of eServices between the health care providers. Over 100,000 eReferral messages (40 %) were transferred between health care providers. Interactive eConsultations enable supervised care leading to the reduction of outpatient visits and more timely appointments. One third (10/31) of the municipal health centers are connected to the clinics in the Helsinki University Central Hospital by the eReferral system. The link directory service extends the dimensions of networking between organizations by combining legacy systems within regional primary and secondary care. The link directory is an interface to diverse patient information systems, like HUSpacs, containing links pointing to the actual patient data located in remote information systems. The original data including images can be viewed with a web browser, but data can be accessed only with the patient's informed consent. Currently the reference data base includes 9.5 million links from 1.4 million patients with over 2.000 daily users. We aim to create a new working environment for professionals by incorporation of innovative information and communication technology, new organization of work and re-engineering of workflows. In the near-future, the citizen will have an active role participating in decisions on his care, carrying out guided self-care and taking steps of pro-active prevention.

Managing diabetes care using an integrated regional e-health approach.

A total of 175 patients with Types 1 and 2 diabetes in primary care and university hospital outpatient departments were randomized into a study group (n = 101) or usual care (n = 74). The study group used an e-health application with a diabetes management system and a home care link. Usual care did not involve e-health, i.e. the patients made regular general practitioner visits about every three months. After 12 months HbA1c decreased significantly in both groups of patients. The differences were small, but HbA1c was significantly lower in the study group than the controls. Diastolic blood pressure, fasting plasma glucose, serum total cholesterol, serum LDL-cholesterol and serum triglycerides were significantly lower in the study than in the control group. This was achieved with fewer visits by study patients to doctors and nurses. Use of e-health in diabetes care for 12 months was able to provide equivalent diabetic control to usual care, and improved cardiovascular risk factors.

UUMA. Regional eHealth services in the hospital district of Helsinki and Uusimaa (HUS).

The UUMA approach is based on a stepwise implementation of integrated regional healthcare services to create a virtually borderless healthcare organisation--a patient centred virtual workspace. In the virtual workspace multi-professional teams and patients collaborate and share information regardless of time and place. Presently the regional ehealth network is comprised of four different integrated services between primary, secondary and tertiary care within the county of Uusimaa. The strategic healthcare modules consist of an (1) ereferral and econsultation network, (2) a knowledge-based disease management platform, (3) PACS system and (4) a universal model for integrated regional services between professionals and patients by a link directory service. The ereferral between primary and secondary care not only speeds up the transfer, but also offers an option for communication in the form of econsultation between general practitioners and hospital specialists. By sharing information and knowledge remote econsultations create a new working environment for integrated delivery of eServices between the health care providers. Last year over 60,000 eReferrals were transferred between health care providers. When associated with viewing of patient data through the link directory, interactive econsultations enable supervised care leading to the reduction of outpatient visits and more timely appointments. The link directory service extends the dimensions of networking between organizations by combining legacy systems within regional primary and secondary care. The link directory is an interface to diverse patient information systems, like HUSpacs, containing links pointing to the actual patient data located in remote information systems. The original data including images can be viewed with a web browser, but data can be accessed only with the patient's informed consent. The chronic disease management system is disease specific: information is utilised in parallel to viewing other relevant medical data through the link directory. We aim to create a new working environment for professionals by incorporation of innovative information and communication technology, new organisation of work and re-engineering of workflows. The citizen has an active role in deciding on the use of his medical information, participating in decisions on his care, carrying out guided self-care and taking steps of pro-active prevention.

Realtime teleconsultations versus face-to-face consultations in dermatology: immediate and six-month outcome.

We evaluated the outcome of both realtime teleconsultations and face-to-face consultations in dermatology. Forty-six patients were enrolled in an open controlled study. Twenty-nine patients (60%) answered the questionnaire sent to them after six months. Over the six-month follow-up, similar proportions of the two patient groups had visited a general practitioner or a specialist in the consulting hospital. At follow-up, overall patient satisfaction with the consultation, measured on a linear analogue scale (0-10), had fallen only slightly and to the same extent after both types of consultation, that is by 1.2 (SD 3.7) after realtime teleconsultations and by 1.4 (SD 4.5) after face-to-face consultations. The proportions of patients who would prefer the same mode of consultation for their next appointment had decreased from 83% to 50% in the realtime teleconsultation group and from 83% to 62% in the face-to-face consultation group. However, in neither group was the change significant. The study suggests that patient satisfaction with teleconsultation is well preserved after six months.

Integrated regional services: are working process changes desirable and achievable?

In the hospital district of Helsinki and Uusimaa, 32 municipalities with one or more health centres provide primary care to their residents. Legal and organizational barriers between primary care and hospital care impede the continuity of patient care. Integrating primary and secondary care with the aid of information technology may facilitate a virtual electronic patient record, in which the viewing of images and other patient data is possible regardless of the organization that produced them. For example, in one trial, diabetic patients sent their home blood glucose measurements by modem to their health centre. Preliminary observations suggest that they could increase their glucose testing largely because they were able to transmit the results to the database and receive teleconsultations. Also, a picture archiving and communication system (PACS) has been in operation in two clinics of the Helsinki University Central Hospital for over two years and seven hospitals had become filmless by the end of 2001. A regional PACS is planned to be completed by the year 2004.

Integrated regional services: are working process changes desirable and achievable?

In the hospital district of Helsinki and Uusimaa, 32 municipalities with one or more health centres provide primary care to their residents. Legal and organizational barriers between primary care and hospital care impede the continuity of patient care. Integrating primary and secondary care with the aid of information technology may facilitate a virtual electronic patient record, in which the viewing of images and other patient data is possible regardless of the organization that produced them. For example, in one trial, diabetic patients sent their home blood glucose measurements by modem to their health centre. Preliminary observations suggest that they could increase their glucose testing largely because they were able to transmit the results to the database and receive teleconsultations. Also, a picture archiving and communication system (PACS) has been in operation in two clinics of the Helsinki University Central Hospital for over two years and seven hospitals had become filmless by the end of 2001. A regional PACS is planned to be completed by the year 2004.