"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.

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).

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.

Pulmonary embolism after discharge for COVID-19: A report of two cases.

Previous studies have found critically ill patients with COVID-19 to have an increased risk of thromboembolic complications. In this case report of two patients admitted with symptomatic COVID-19, both patients developed pulmonary embolism within a few days after hospital discharge. Both patients received thromboprophylaxis and had an increasing fibrin D-dimer during their hospital stay. Continued thromboprophylaxis after hospital discharge may be indicated for patients with COVID-19, especially for patients at high risk of thrombosis with elevated levels of fibrin D-dimer.

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.

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.

"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.

Influence of rosiglitazone treatment on beta-cell function in type 2 diabetes: evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility.

Thiazolidinediones have well-established insulin-sensitizing effects. Their impact on insulin secretion is less clarified. Consequently, we sought to determine potential effects of a thiazolidinedione (rosiglitazone) on the beta-cell function. Twenty type 2 diabetic individuals were randomized to receive rosiglitazone (rosi) 4 mg twice daily or placebo (pla) for 13 wk. Before treatment and at the end of the treatment period, the patients underwent an iv glucose tolerance test (0.3 g/kg), a hyperglycemic (15 mmol/liter) clamp with arginine (5 g) stimulation, assessment of baseline high-frequency insulin pulsatility, and glucose-entrained insulin pulsatility (6 mg/kg.min every 10 min), and a hyperinsulinemic euglycemic clamp. Fasting plasma glucose was reduced (pla, 8.2 +/- 2.1 vs. 8.8 +/- 2.6 mmol/liter; rosi, 8.6 +/- 7.1 vs. 7.1 +/- 1.2 mmol/liter; P < 0.01), and insulin sensitivity was increased by rosiglitazone treatment (M value: pla, 5.3 +/- 1.8 vs. 5.4 +/- 1.6 mg/kg.min; rosi, 5.9 +/- 2.2 vs. 7.4 +/- 1.3 mg/kg.min; P = 0.05). First-phase insulin secretion and insulin secretory capacity were unaffected. Glucose-entrained insulin secretion was increased as assessed by spectral power analysis (P = 0.05). In conclusion, rosiglitazone treatment for 3 months in type 2 diabetic patients exerts no action on insulin secretion per se. Improved glucose-entrained high-frequency insulin pulsatility suggests an increased ability of the beta-cell to sense and respond to glucose changes within the physiological range.

Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes.

Glucagon-like peptide 1 (GLP-1) is a potent glucose-lowering agent of potential interest for the treatment of type 2 diabetes. To evaluate actions of NN2211, a long-acting GLP-1 derivative, we examined 11 patients with type 2 diabetes, age 59 +/- 7 years (mean +/- SD), BMI 28.9 +/- 3.0 kg/m(2), HbA(1c) 6.5 +/- 0.6%, in a double-blind, placebo-controlled, crossover design. A single injection (10 microg/kg) of NN2211 was administered at 2300 h, and profiles of circulating insulin, C-peptide, glucose, and glucagon were monitored during the next 16.5 h. A standardized mixed meal was served at 1130 h. Efficacy analyses were performed for the fasting (7-8 h) and mealtime (1130-1530 h) periods. Insulin secretory rates (ISR) were estimated by C-peptide deconvolution analysis. Glucose pulse entrainment (6 mg x kg(-1) x min(-1) every 10 min) was evaluated by 1-min sampled measurements of insulin concentrations from 0930 to 1030 h and subsequent time series analysis of the insulin concentration profiles. All results are given as NN2211 versus placebo; statistical analyses were performed by analysis of variance. In the fasting state, plasma glucose was significantly reduced (6.9 +/- 1.0 vs. 8.1 +/- 1.0 mmol/l; P = 0.004), ISR was increased (179 +/- 70 vs. 163 +/- 66 pmol/min; P = 0.03), and plasma glucagon was unaltered (19 +/- 4 vs. 20 +/- 4 pg/ml; P = 0.17) by NN2211. Meal-related area under the curve (AUC)(1130-1530 h) for glucose was markedly reduced (30.6 +/- 2.4 vs. 39.9 +/- 7.3 mmol x l(-1) x h(-1); P < 0.001), ISR AUC(1130-1530 h) was unchanged (118 +/- 32 vs. 106 +/- 27 nmol; P = 0.13), but the increment (relative to premeal values) was increased (65 +/- 22 vs. 45 +/- 11 nmol; P = 0.04). Glucagon AUC(1130-1530 h) was suppressed (77 +/- 18 vs. 82 +/- 17 pmol x l(-1) x h(-1); P = 0.04). Gastric emptying was significantly delayed as assessed by AUC(1130-1530 h) of 3-ortho-methylglucose (400 +/- 84 vs. 440 +/- 70 mg x l(-1) x h(-1); P = 0.02). During pulse entrainment, there was a tendency to increased high frequency regularity of insulin release as measured by a greater spectral power and autocorrelation coefficient (0.05 < P < 0.10). The pharmacokinetic profile of NN2211, as assessed by blood samplings for up to 63 h postdosing, was as follows: T(1/2) = 10.0 +/- 3.5 h and T(max) = 12.4 +/- 1.7 h. Two patients experienced gastrointestinal side effects on the day of active treatment. In conclusion, the long-acting GLP-1 derivative NN2211 effectively reduces fasting as well as meal-related (approximately 12 h postadministration) glycemia by modifying insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

Pulsatile insulin secretion: detection, regulation, and role in diabetes.

Insulin concentrations oscillate at a periodicity of 5-15 min per oscillation. These oscillations are due to coordinate insulin secretory bursts, from millions of islets. The generation of common secretory bursts requires strong within-islet and within-pancreas coordination to synchronize the secretory activity from the beta-cell population. The overall contribution of this pulsatile mechanism dominates and accounts for the majority of insulin release. This review discusses the methods involved in the detection and quantification of periodicities and individual secretory bursts. The mechanism by which overall insulin secretion is regulated through changes in the pulsatile component is discussed for nerves, metabolites, hormones, and drugs. The impaired pulsatile secretion of insulin in type 2 diabetes has resulted in much focus on the impact of the insulin delivery pattern on insulin action, and improved action from oscillatory insulin exposure is demonstrated on liver, muscle, and adipose tissues. Therefore, not only is the dominant regulation of insulin through changes in secretory burst mass and amplitude, but the changes may affect insulin action. Finally, the role of impaired pulsatile release in early type 2 diabetes suggests a predictive value of studies on insulin pulsatility in the development of this disease.