Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis. OBJECTIVES: This study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM. METHODS: Patients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first heart failure hospitalization (HFH). A Cox proportional hazards model was used to calculate HRs and 95% CIs to assess if the effect of vericiguat differed by history of T2DM. RESULTS: Of 5,050 patients enrolled, 3,683 (72.9%) had glycosylated hemoglobin (HbA1c) measured at baseline. Of these, 2,270 (61.6%) had T2DM, 741 (20.1%) had pre-T2DM, 449 (12.2%) did not have T2DM, and 178 (4.8%) had undiagnosed T2DM. The risks of the primary outcome, HFH, and all-cause and cardiovascular mortality were high across all categories. The efficacy of vericiguat on the primary outcome did not differ in patients stratified by T2DM by history (HR: 0.92; 95% CI: 0.81-1.04), T2DM measured by HbA1c (HR: 0.77; 95% CI: 0.49-1.20), and pre-T2DM measured by HbA1c (HR: 0.88; 95% CI: 0.68-1.13) and in those with normoglycemia (HR: 1.02: 95% CI: 0.75-1.39; P for interaction = 0.752). No significant differences were observed in subgroups with respect to the efficacy of vericiguat on HFH and all-cause or cardiovascular death. CONCLUSIONS: In this post hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction regardless of T2DM status. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [Mk-1242-001] [VICTORIA]; NCT02861534).

"Future patient II" telerehabilitation for patients with heart failure: Protocol for a randomized controlled trial.

Background: Heart failure is a global problem affecting millions of people worldwide. Current care of heart failure patients follows standard protocols and often overlooks the patients' specific needs, which leads to low compliance in the rehabilitation phase. Telerehabilitation, where the patients communicate with health care professionals about their rehabilitation program and monitor their vital signs, aims to increase the degree of compliance as well as enhancing their quality of life. Objective: The aim of this study is to investigate whether application of the Future Patient Telerehabilitation Program II can improve the health-related quality of life for patients with heart failure. Methods: A randomized controlled trial will be conducted. A total of 70 patients will be enrolled, 35 in the intervention group, 35 in the control group. The intervention group will follow an add-on to traditional care, while the control group will follow the conventional Danish cardiac rehabilitation program, which is based on periodic visits to the clinic. The patients will be followed for a period of six months. The intervention group will have access to an online HeartPortal and will use various home-based devices for self-monitoring. The primary outcome to be investigated is health-related quality of life as measured by the EuroQol-5 Dimension. Secondary outcomes are the number of visits to the outpatient clinic, number of readmissions and number of tele-communications contacts (phone and video) with health care professionals. The primary and secondary outcomes will be assessed using questionnaires and through the data generated by digital technologies for self-monitoring. Results: Enrolment began in August 2020. The results will be published in peer-reviewed journals. Results from the Future Patient II Telerehabilitation program are expected to be published in 2024. Discussion: This study is a further development of the Future Patient Telerehabilitation I study, and it is expected to explore the use of video consultation and a weight calculator in relation to telerehabilitation as well as the quality of life for heart failure patients. Conclusion: The expected outcomes are increased quality of life, increased number of phone- and video-consultations with health-care professionals, and the enhanced ability of patients to manage their own disease with the use of a calculator for weight.

Relevance of the Viborg Population Based Screening Programme (VISP) for Cardiovascular Conditions Among 67 Year Olds: Attendance Rate, Prevalence, and Proportion of Initiated Cardiovascular Medicines Stratified By Sex.

OBJECTIVE: To report sex specific overall attendance rate, prevalence of screen detected cardiovascular conditions, proportion of unknown conditions before screening, and proportion initiating prophylactic medicine among 67 year olds in Denmark. DESIGN: Cross sectional cohort study. METHODS: Since 2014, all 67 year olds in Viborg, Denmark, have been invited to screening for abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), carotid plaque (CP), hypertension, cardiac disease, and type 2 diabetes. Individuals with AAA, PAD, and or CP are recommended cardiovascular prophylaxis. Combining data with registries has facilitated estimation of unknown screen detected conditions. Up to August 2019, 5 505 had been invited; registry data were available for the first 4 826 who were invited. RESULTS: The attendance rate was 83.7%, without sex difference. Screen detected prevalence was significantly lower among women than men: AAA, 5 (0.3%) vs. 38 (1.9%) (p < .001); PAD, 90 (4.5%) vs. 134 (6.6%) (p = .011); CP, 641 (31.8%) vs. 907 (44.8%) (p < .001); arrhythmia, 26 (1.4%) vs. 77 (4.2%) (p < .001); blood pressure ≥ 160/100 mmHg, 277 (13.8%) vs. 346 (17.1%) (p = .004); and HbA1c ≥ 48 mmol/mol, 155 (7.7%) vs. 198 (9.8%) (p = .019), respectively. Pre-screening proportions of unknown conditions were particularly high for AAA (95.4%) and PAD (87.5%). AAA, PAD, and or CP were found in 1 623 (40.2%), of whom 470 (29.0%) received pre-screening antiplatelets and 743 (45.8%) lipid lowering therapy. Furthermore, 413 (25.5%) started antiplatelet therapy and 347 (21.4%) started lipid lowering therapy. Only smoking was significantly associated with all vascular conditions in multivariable analysis: odds ratios (ORs) for current smoking were AAA 8.11 (95% CI 2.27 - 28.97), PAD 5.60 (95% CI 3.61 - 8.67) and CP 3.64 (95% CI 2.95 - 4.47). CONCLUSION: The attendance rate signals public acceptability for attending cardiovascular screening. Men had more screen detected conditions than women, but prophylactic medicine was started equally frequently in both sexes. Sex specific cost effectiveness follow up is warranted.

Protocol for a cohort study to evaluate the effectiveness and cost-effectiveness of general population screening for cardiovascular disease: the Viborg Screening Programme (VISP).

INTRODUCTION: The prevalence of cardiovascular disease (CVD) is increasing. Furthermore, asymptomatic individuals may not receive timely preventive initiatives to minimise the risk of further CVD events. Paradoxically, 80% of CVD events are preventable by early detection, followed by prophylactic initiatives. Consequently, we introduced the population-based Viborg Screening Programme (VISP) for subclinical and manifest CVD, focusing on commonly occurring, mainly asymptomatic conditions, followed by prophylactic initiatives.The aim of the VISP was to evaluate the health benefits, harms and cost-effectiveness of the VISP from a healthcare sector perspective. Furthermore, we explored the participants' perspectives. METHODS AND ANALYSIS: From August 2014 and currently ongoing, approximately 1100 men and women from the Viborg municipality, Denmark, are annually invited to screening for abdominal aortic aneurysm, peripheral arterial disease, carotid plaque, hypertension, diabetes mellitus and cardiac arrhythmia on their 67th birthday. A population from the surrounding municipalities without access to the VISP acts as a control. The VISP invitees and the controls are followed on the individual level by nationwide registries. The primary outcome is all-cause mortality, while costs, hospitalisations and deaths from CVD are the secondary endpoints.Interim evaluations of effectiveness and cost-effectiveness are planned every 5 years using propensity score matching followed by a Cox proportional hazards regression analysis by the 'intention-to-treat' principle. Furthermore, censoring-adjusted incremental costs, life-years and quality-adjusted life-years are estimated. Finally, the participants' perspectives are explored by semistructured face-to-face interviews, with participant selection representing participants with both negative and positive screening results. ETHICS AND DISSEMINATION: The VISP is not an interventional trial. Therefore, approval from a regional scientific ethical committee is not needed. Data collection from national registries was approved by the Regional Data Protection Agency (record no. 1-16-02-232-15). We ensure patient and public involvement in evaluating the acceptability of VISP by adopting an interviewing approach in the study. TRIAL REGISTRATION NUMBER: NCT03395509.

Increased motivation for and use of digital services in heart failure patients participating in a telerehabilitation program: a randomized controlled trial.

Background: eHealth literacy (eHL) may be an important factor in the adoption of telerehabilitation. However, little is known about how telerehabilitation affects patients' eHL. The current study evaluated changes over time in eHL for heart failure (HF) patients in a telerehabilitation program (the Future Patient Program) compared to a traditional rehabilitation program. Methods: As part of a randomized controlled trial comparing telerehabilitation with traditional rehabilitation, 137 HF patients completed the eHealth Literacy Questionnaire (eHLQ) at 6 and 12 months of their respective rehabilitation programs. Results: At 6 months, the telerehabilitation group indicated higher levels of 'using technology to process health information' and 'motivated to engage with digital services'. This difference was consistent over time, and we found no other differences between groups or over time with regard to eHL. Conclusions: Providing a digital toolbox for processing health information to HF patients may aid in increasing their eHL, motivation, and ability to engage with digital services in HF patients. Especially, if the technology is designed to support patient needs in terms of the educational content of the program. Preferably technology should be provided early on in the rehabilitation process to ensure optimal outcome. Trial Registration: The study was registered in ClinicalTrials.gov (NCT03388918).

Impacts of land use, climate change and hydrological model structure on nitrate fluxes: Magnitudes and uncertainties.

Nitrate pollution and eutrophication are of increasing concern in agriculturally dominated regions, and with projected future climate changes, these issues are expected to worsen for both surface and groundwater. Changes in land use and management have the potential to mitigate some of these concerns. However, to what extent these changes will interact is unknown, and are associated with significant uncertainty. Here, we estimate nitrate fluxes and contributions of major uncertainty sources (variance decomposition analysis) affecting nitrate leaching from the root zone and river load from groundwater sources for an agricultural catchment in Denmark under future changes (2080-2099) in climate (four climate models) and land use (four land use scenarios). To investigate the uncertainty from impact model choice, two different agro-hydrological models (SWAT and DAISY-MIKE SHE) both traditionally used for nitrate impact assessments are used for projecting these effects. On average, nitrate leaching from the root zone increased by 55%-123% due to different climate models, while the impact of land use scenarios showed changes between -9% and 88%, with similar projections for river loads, while the worst-case combination of the three factors yielded a fivefold increase in nitrate transport. Thus, in the future, major land use changes will be necessary to mitigate nitrate pollution likely in combination with other measures such as advanced management and farming technologies and differentiated regulation. The two agro-hydrological models showed substantially different reaction patterns and magnitude of nitrate fluxes, and while the largest uncertainty source was the land use scenarios for both models, DAISY-MIKE SHE was to a higher degree affected by climate model choice. The dominating uncertainty source was found to be the agro-hydrological model; however, both uncertainties related to land use scenario and climate model were important, thus highlighting the need to include all influential factors in future nitrate flux impact studies.

Web Portals for Patients With Chronic Diseases: Scoping Review of the Functional Features and Theoretical Frameworks of Telerehabilitation Platforms.

BACKGROUND: The COVID-19 pandemic has required an increased need for rehabilitation activities applicable to patients with chronic diseases. Telerehabilitation has several advantages, including reducing clinic visits by patients vulnerable to infectious diseases. Digital platforms are often used to assist rehabilitation services for patients in remote settings. Although web portals for medical use have existed for years, the technology in telerehabilitation remains a novel method. OBJECTIVE: This scoping review investigated the functional features and theoretical approaches of web portals developed for telerehabilitation in patients with chronic diseases. METHODS: PubMed and Web of Science were reviewed to identify articles associated with telerehabilitation. Of the 477 nonduplicate articles reviewed, 35 involving 14 portals were retrieved for the scoping review. The functional features, targeted diseases, and theoretical approaches of these portals were studied. RESULTS: The 14 portals targeted patients with chronic obstructive pulmonary disease, cardiovascular, osteoarthritis, multiple sclerosis, cystic fibrosis diseases, and stroke and breast cancer survivors. Monitoring/data tracking and communication functions were the most common, followed by exercise instructions and diary/self-report features. Several theoretical approaches, behavior change techniques, and motivational techniques were found to be utilized. CONCLUSIONS: The web portals could unify and display multiple types of data and effectively provide various types of information. Asynchronous correspondence was more favorable than synchronous, real-time interactions. Data acquisition often required assistance from other digital tools. Various functions with patient-centered principles, behavior change strategies, and motivational techniques were observed for better support shifting to a healthier lifestyle. These findings suggested that web portals for telerehabilitation not only provided entrance into rehabilitation programs but also reinforced participant-centered treatment, adherence to rehabilitation, and lifestyle changes over time.

Effects of Telerehabilitation Interventions on Heart Failure Management (2015-2020): Scoping Review.

BACKGROUND: Heart failure is one of the world's most frequently diagnosed cardiovascular diseases. An important element of heart failure management is cardiac rehabilitation, the goal of which is to improve patients' recovery, functional capacity, psychosocial well-being, and health-related quality of life. Patients in cardiac rehabilitation may lack sufficient motivation or may feel that the rehabilitation process does not meet their individual needs. One solution to these challenges is the use of telerehabilitation. Although telerehabilitation has been available for several years, it has only recently begun to be utilized in heart failure studies. Especially within the past 5 years, we now have several studies focusing on the effectiveness of telerehabilitation for heart failure management, all with varying results. Based on a review of these studies, this paper offers an assessment of the effectiveness of telerehabilitation as applied to heart failure management. OBJECTIVE: The aim of this scoping review was to assess the effects of telerehabilitation in the management of heart failure by systematically reviewing the available scientific literature within the period from January 1, 2015, to December 31, 2020. METHODS: The literature search was carried out using PubMed and EMBASE. After duplicates were removed, 77 articles were screened and 12 articles were subsequently reviewed. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews) guidelines. As measures of the effectiveness of telerehabilitation, the following outcomes were used: patients' quality of life, physical capacity, depression or anxiety, and adherence to the intervention. RESULTS: A total of 12 articles were included in this review. In reviewing the effects of telerehabilitation for patients with heart failure, it was found that 4 out of 6 randomized controlled trials (RCTs), a single prospective study, and 4 out of 5 reviews reported increased quality of life for patients. For physical capacity, 4 RCTs and 3 systematic reviews revealed increased physical capacity. Depression or depressive symptoms were reported as being reduced in 1 of the 6 RCTs and in 2 of the 5 reviews. Anxiety or anxiety-related symptoms were reported as reduced in only 1 review. High adherence to the telerehabilitation program was reported in 4 RCTs and 4 reviews. It should be mentioned that some of the reviewed articles described the same studies although they employed different outcome measures. CONCLUSIONS: It was found that there is a tendency toward improvement in patients' quality of life and physical capacity when telerehabilitation was used in heart failure management. The outcome measures of depression, anxiety, and adherence to the intervention were found to be positive. Additional research is needed to determine more precise and robust effects of telerehabilitation.

Motivating patients in cardiac rehabilitation programs: A multicenter randomized controlled trial.

Concerns have been raised about motivation and psychological distress when implementing telerehabilitation in patients with heart failure. The current study compared conventional and telerehabilitation in two groups (n=67; n=70) of patients with heart failure at 0, 6, and 12 months on measures of motivation (Self-Determination Theory measures) and psychological distress (Hospital Anxiety and Depression scale). We found no significant changes in motivation across groups, although our telerehabilitation group had a slightly lower level of controlled motivation and higher levels of relatedness. In addition, there were no differences between groups with regard to psychological distress. This study demonstrates that telerehabilitation motivates patients with heart failure to the same degree as conventional rehabilitation, and that telerehabilitation is not associated with increased psychological distress. As such, telerehabilitation offers an alternative to conventional rehabilitation and addresses some of the barriers for participating in rehabilitation identified in the literature.

Patient-Reported Outcomes From Patients With Heart Failure Participating in the Future Patient Telerehabilitation Program: Data From the Intervention Arm of a Randomized Controlled Trial.

BACKGROUND: More than 37 million people worldwide have been diagnosed with heart failure, which is a growing burden on the health sector. Cardiac rehabilitation aims to improve patients' recovery, functional capacity, psychosocial well-being, and health-related quality of life. However, cardiac rehabilitation programs have poor compliance and adherence. Telerehabilitation may be a solution to overcome some of these challenges to cardiac rehabilitation by making it more individualized. As part of the Future Patient Telerehabilitation program, a digital toolbox aimed at enabling patients with heart failure to monitor and evaluate their own current status has been developed and tested using data from a patient-reported outcome questionnaire that the patient filled in every alternate week for 1 year. OBJECTIVE: The aim of this study is to evaluate the changes in quality of life and well-being among patients with heart failure, who are participants in the Future Patient Telerehabilitation program over the course of 1 year. METHODS: In total, 140 patients were enrolled in the Future Patient Telerehabilitation program and randomized into either the telerehabilitation group (n=70) or the control group (n=70). Of the 70 patients in the telerehabilitation group, 56 (80.0%) answered the patient-reported outcome questionnaire and completed the program, and these 56 patients comprised the study population. The patient-reported outcomes consisted of three components: (1) questions regarding the patients' sleep patterns assessed using the Spiegel Sleep Questionnaire; (2) measurements of physical limitations, symptoms, self-efficacy, social interaction, and quality of life assessed using the Kansas City Cardiomyopathy Questionnaire in 10 dimensions; and (3) 5 additional questions regarding psychological well-being that were developed by the research group. RESULTS: The changes in scores during 1 year of the study were examined using 1-sample Wilcoxon signed-rank tests. There were significant differences in the scores for most of the slopes of the scores from the dimensions of the Kansas City Cardiomyopathy Questionnaire (P<.05). CONCLUSIONS: There was a significant increase in clinical and social well-being and quality of life during the 1-year period of participating in a telerehabilitation program. These results suggest that patient-reported outcome questionnaires may be used as a tool for patients in a telerehabilitation program that can both monitor and guide patients in mastering their own symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT03388918; https://clinicaltrials.gov/ct2/show/NCT03388918.

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT).

OBJECTIVES: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT). METHODS: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years. RESULTS: As of May 2020, 296 patients have been randomized at 20 centers in Denmark. CONCLUSION: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Clinical Outcomes and Response to Vericiguat According to Index Heart Failure Event: Insights From the VICTORIA Trial.

Importance: The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH. Objective: To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. Design, Setting, and Participants: Analysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020. Intervention: Vericiguat titrated to 10 mg daily vs placebo. Main Outcomes and Measures: The primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. Results: Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms. Conclusions and Relevance: Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF. Trial Registration: ClinicalTrials.gov Identifier: NCT02861534.

Non-Contact Respiratory Measurement Using a Depth Camera for Elderly People.

Measuring respiration at home for cardiac patients, a simple method that can detect the patient's natural respiration, is needed. The purpose of this study was to develop an algorithm for estimating the tidal volume (TV) and respiratory rate (RR) from the depth value of the chest and/or abdomen, which were captured using a depth camera. The data of two different breathing patterns (normal and deep) were acquired from both the depth camera and the spirometer. The experiment was performed under two different clothing conditions (undressed and wearing a T-shirt). Thirty-nine elderly volunteers (male = 14) were enrolled in the experiment. The TV estimation algorithm for each condition was determined by regression analysis using the volume data from the spirometer as the objective variable and the depth motion data from the depth camera as the explanatory variable. The RR estimation was calculated from the peak interval. The mean absolute relative errors of the estimated TV for males were 14.0% under undressed conditions and 10.7% under T-shirt-wearing conditions; meanwhile, the relative errors for females were 14.7% and 15.5%, respectively. The estimation error for the RR was zero out of a total of 206 breaths under undressed conditions and two out of a total of 218 breaths under T-shirt-wearing conditions for males. Concerning females, the error was three out of a total of 329 breaths under undressed conditions and five out of a total of 344 breaths under T-shirt-wearing conditions. The developed algorithm for RR estimation was accurate enough, but the estimated occasionally TV had large errors, especially in deep breathing. The cause of such errors in TV estimation is presumed to be a result of the whole-body motion and inadequate setting of the measurement area.

Nitrate leaching losses from two Baltic Sea catchments under scenarios of changes in land use, land management and climate.

Pollution with excess nutrients deteriorate the water quality of the Baltic Sea. The effect of combined land use and climate scenarios on nitrate leaching and nitrogen (N) loads to surface waters from two Baltic Sea catchments (Norsminde in Denmark and Kocinka in Poland) was explored using different models; the NLES and Daisy models for nitrate leaching, and MIKE SHE or MODFLOW/MT3DMS for N transport. Three Shared Socioeconomic Pathways (SSP1, SSP2 and SSP5) defined change in land use and agricultural activities. The climate change scenarios covered 2041-2060 compared with 1991-2010 under RCP8.5, applying four different climate models. Increases in predicted N-load from climate change vary from 20 to 60% depending on climate model. SSPs moderate these N-load changes with small changes for SSP1 to large increases for SSP5, with greater increases for Norsminde than Kocinka due to land use differences. This stresses needs for new measures and governing schemes to meet sustainability targets.

Future socioeconomic conditions may have a larger impact than climate change on nutrient loads to the Baltic Sea.

The Baltic Sea is suffering from eutrophication caused by nutrient discharges from land to sea, and these loads might change in a changing climate. We show that the impact from climate change by mid-century is probably less than the direct impact of changing socioeconomic factors such as land use, agricultural practices, atmospheric deposition, and wastewater emissions. We compare results from dynamic modelling of nutrient loads to the Baltic Sea under projections of climate change and scenarios for shared socioeconomic pathways. Average nutrient loads are projected to increase by 8% and 14% for nitrogen and phosphorus, respectively, in response to climate change scenarios. In contrast, changes in the socioeconomic drivers can lead to a decrease of 13% and 6% or an increase of 11% and 9% in nitrogen and phosphorus loads, respectively, depending on the pathway. This indicates that policy decisions still play a major role in climate adaptation and in managing eutrophication in the Baltic Sea region.

Reactive nitrogen in a clay till hill slope field system.

To assess the contribution of reactive nitrogen from groundwater to surface waters, we need more knowledge on how reactive nitrogen behaves in the glacial till systems underlying many agricultural fields. Groundwater sampled from suction cups and piezometers placed in the glacial till underlying a winter wheat field shows the nitrate concentration in water leaching to deeper than 2 m below ground surface (mbg) is ~ 60 mg L-1. Within 5 mbg, all of the nitrate is removed and this appears to take place within a redox zone rather than at a sharp redox front. Ammonium released from the till is negligible. A 2D dataset reveals that the depth to the redox zone undulates between 3 and 5 mbg, perhaps a result of local variations in infiltration. It appears that the nitrate is generally reduced by the oxidation of pyrite and locally by organic matter in lenses within the till.

"Future Patient" Telerehabilitation for Patients With Heart Failure: Protocol for a Randomized Controlled Trial.

BACKGROUND: Cardiovascular disease is the leading cause of mortality worldwide, accounting for 13%-15% of all deaths. Cardiac rehabilitation has poor compliance and adherence. Telerehabilitation has been introduced to increase patients' participation, access, and adherence with the help of digital technologies. The target group is patients with heart failure. A telerehabilitation program called "Future Patient" has been developed and consists of three phases: (1) titration of medicine (0-3 months), (2) implementation of the telerehabilitation protocols (3 months), and (3) follow-up with rehabilitation in everyday life (6 months). Patients in the Future Patient program measure their blood pressure, pulse, weight, number of steps taken, sleep, and respiration and answer questions online regarding their well-being. All data are transmitted and accessed in the HeartPortal by patients and health care professionals. OBJECTIVE: The aim of this paper is to describe the research design, outcome measures, and data collection techniques in the clinical test of the Future Patient Telerehabilitation Program for patients with heart failure. METHODS: A randomized controlled study will be performed. The intervention group will follow the Future Patient Telerehabilitation program, and the control group will follow the traditional cardiac rehabilitation program. The primary outcome is quality of life measured by the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes are development of clinical data; illness perception; motivation; anxiety and depression; health and electronic health literacy; qualitative exploration of patients', spouses', and health care professionals' experiences of participating in the telerehabilitation program; and a health economy evaluation of the program. Outcomes were assessed using questionnaires and through the data generated by digital technologies. RESULTS: Data collection began in December 2016 and will be completed in October 2019. The study results will be published in peer-reviewed journals and presented at international conferences. Results from the Future Patient Telerehabilitation program are expected to be published by the spring of 2020. CONCLUSIONS: The expected outcomes are increased quality of life, increased motivation and illness perception, reduced anxiety and depressions, improved electronic health literacy, and health economics benefits. We expect the study to have a clinical impact for future telerehabilitation of patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT03388918; https://clinicaltrials.gov/ct2/show/NCT03388918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14517.

Spatially differentiated regulation: Can it save the Baltic Sea from excessive N-loads?

The Baltic Sea Action Plan and the EU Water Framework Directive both require substantial additional reductions of nutrient loads (N and P) to the marine environment. Focusing on nitrogen, we present a widely applicable concept for spatially differentiated regulation, exploiting the large spatial variations in the natural removal of nitrate in groundwater and surface water. By targeting mitigation measures towards areas where nature's own capacity for removal is low, spatially differentiated regulation can be more cost-effective than the traditional uniform regulation. We present a methodology for upscaling local modelling results on targeted measures at field scale to Baltic Sea drainage basin scale. The paper assesses the potential gain and discusses key challenges related to implementation of spatially differentiated regulation, including the need for more scientific knowledge, handling of uncertainties, practical constraints related to agricultural practice and introduction of co-governance regimes.

Effect of long-term remote ischemic conditioning on inflammation and cardiac remodeling.

Background. Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion injury and may have beneficial effects in patients with stable cardiovascular disease. We investigated the effect of long-term RIC treatment in patients with chronic ischemic heart failure (CIHF). Methods. Prespecified post-hoc analysis of a prospective, exploratory and outcome-assessor blinded study. Twenty-one patients with compensated CIHF and 21 matched controls without heart failure or ischemic heart disease were treated with RIC once daily for 28 ± 4 days. RIC was conducted as 4 cycles of 5 minutes upper arm ischemia followed by 5 minutes of reperfusion. We evaluated circulating markers of inflammation and cardiac remodeling at baseline and following long-term RIC. Results. RIC reduced C-reactive protein from 1.5 (0.6-2.5) to 1.3 (0.6-2.1) mg/l following long-term RIC treatment (p = .02) and calprotectin from 477 (95% CI 380 to 600) to 434 (95% CI 354 to 533) ng/ml (p = .03) in patients with CIHF, but not in matched controls. Overall, RIC did not affect circulating markers related to adaptive or innate immunology or cardiac remodeling in patients with CIHF. Among patients with CIHF and N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels above the geometric mean of 372 ng/l, long-term RIC treatment reduced soluble ST2 (n = 9) from 22.0 ± 3.7 to 20.3 ± 3.9 ng/ml following long-term RIC treatment (p = .01). Conclusion. Our findings suggest that long-term RIC treatment has mild anti-inflammatory effects in patients with compensated CIHF and anti-remodeling effects in those with increased NT-proBNP levels. This should be further investigated in a randomized sham-controlled trial.