Digital Health Transformation of Integrated Care in Europe: Overarching Analysis of 17 Integrated Care Programs.

BACKGROUND: Digital health tools comprise a wide range of technologies to support health processes. The potential of these technologies to effectively support health care transformation is widely accepted. However, wide scale implementation is uneven among countries and regions. Identification of common factors facilitating and hampering the implementation process may be useful for future policy recommendations. OBJECTIVE: The aim of this study was to analyze the implementation of digital health tools to support health care and social care services, as well as to facilitate the longitudinal assessment of these services, in 17 selected integrated chronic care (ICC) programs from 8 European countries. METHODS: A program analysis based on thick descriptions-including document examinations and semistructured interviews with relevant stakeholders-of ICC programs in Austria, Croatia, Germany, Hungary, the Netherlands, Norway, Spain, and the United Kingdom was performed. A total of 233 stakeholders (ie, professionals, providers, patients, carers, and policymakers) were interviewed from November 2014 to September 2016. The overarching analysis focused on the use of digital health tools and program assessment strategies. RESULTS: Supporting digital health tools are implemented in all countries, but different levels of maturity were observed among the programs. Only few ICC programs have well-established strategies for a comprehensive longitudinal assessment. There is a strong relationship between maturity of digital health and proper evaluation strategies of integrated care. CONCLUSIONS: Notwithstanding the heterogeneity of the results across countries, most programs aim to evolve toward a digital transformation of integrated care, including implementation of comprehensive assessment strategies. It is widely accepted that the evolution of digital health tools alongside clear policies toward their adoption will facilitate regional uptake and scale-up of services with embedded digital health tools.

Wearable cardioverter defibrillators for the prevention of sudden cardiac arrest: a health technology assessment and patient focus group study.

AIM: To summarize the evidence on clinical effectiveness and safety of wearable cardioverter defibrillator (WCD) therapy for primary and secondary prevention of sudden cardiac arrest in patients at risk. METHODS: We performed a systematic literature search in databases including MEDLINE via OVID, Embase, the Cochrane Library, and CRD (DARE, NHS-EED, HTA). The evidence obtained was summarized according to GRADE methodology. A health technology assessment (HTA) was conducted using the HTA Core Model® for rapid relative effectiveness assessment. Primary outcomes for the clinical effectiveness domain were all-cause and disease-specific mortality. Outcomes for the safety domain were adverse events (AEs) and serious adverse events (SAEs). A focus group with cardiac disease patients was conducted to evaluate ethical, organizational, patient, social, and legal aspects of the WCD use. RESULTS: No randomized- or non-randomized controlled trials were identified. Non-comparative studies (n=5) reported AEs including skin rash/itching (6%), false alarms (14%), and palpitations/light-headedness/fainting (9%) and discontinuation due to comfort/lifestyle issues (16-22%), and SAEs including inappropriate shocks (0-2%), unsuccessful shocks (0-0.7%), and death (0-0.3%). The focus group results reported that experiencing a sense of security is crucial to patients and that the WCD is not considered an option for weeks or even months due to expected restrictions in living a "normal" life. CONCLUSION: The WCD appears to be relatively safe for short-to-medium term, but the quality of existing evidence is very low. AEs and SAEs need to be more appropriately reported in order to further evaluate the safety of the device. High-quality comparative evidence and well-described disease groups are required to assess the effectiveness of the WCD and to determine which patient groups may benefit most from the intervention.

Auxin amidohydrolases from Brassica rapa cleave the alanine conjugate of indolepropionic acid as a preferable substrate: a biochemical and modeling approach.

Two auxin amidohydrolases, BrIAR3 and BrILL2, from Chinese cabbage [Brassica rapa L. ssp. pekinensis (Lour.) Hanelt] were produced by heterologous expression in Escherichia coli, purified, and screened for activity towards N-(indol-3-ylacetyl)-L-alanine (IAA-Ala) and the long-chain auxin-amino acid conjugates, N-[3-(indol-3-yl)propionyl]-L-alanine (IPA-Ala) and N-[4-(indol-3-yl)butyryl]-L-alanine (IBA-Ala). IPA-Ala was shown to be the favored substrate of both enzymes, but BrILL2 was approximately 15 times more active than BrIAR3. Both enzymes cleaved IBA-Ala and IAA-Ala to a lesser extent. The enzyme kinetics were measured for BrILL2 and the obtained parameters suggested similar binding affinities for the long-chain auxin-amino acid conjugates (IPA-Ala and IBA-Ala). The velocity of the hydrolyzing reaction decreased in the order IPA-Ala > IBA-Ala > IAA-Ala. In a root growth bioassay, higher growth inhibition was caused by IPA-Ala and IBA-Ala in comparison with IAA-Ala. Neither these conjugates nor the corresponding free auxins affected the expression of the BrILL2 gene. A modeling study revealed several possible modes of IPA-Ala binding to BrILL2. Based on these results, two possible scenarios for substrate hydrolysis are proposed. In one the metal binding water is activated by the carboxyl group of the substrate itself, and in the other by a glutamate residue from the active site of the enzyme.