You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Background {#s1}
==========

Children with congenital heart disease (CHD) show reduced motor competence or motor ability ([@B1]--[@B4]) as well as limitations in fine and gross motor skills ([@B5]--[@B7]). These skill-based limitations from early infancy are tracked into adulthood with further negative effect on health-related physical fitness (HRPF) and muscle strength ([@B8]--[@B11]). That those limitations still exist in the vast majority of children with CHD outline recent projects on health-related physical fitness (HRPF) and cardiovascular health ([@B12]--[@B17]).

These circumstances should in general be a reason to worry and a starting signal for exercise promotions and interventions to overcome such deficits to facilitate normal social integration and school sport participation as early as possible. Unfortunately, a review from 2013 outlines that exercise interventions are still underutilized, because of the relatively low prevalence of single types of CHD and the proximity to the study centers ([@B18]). One drawback is that the primary outcome of those studies always refers to improvements in peak oxygen uptake, while any forms of motor-related competences are of minor interest. This is probably the case, because motor-related competences do not represent a hard clinical endpoint like parameters derived from cardiopulmonary exercise testing ([@B19]--[@B21]). Another drawback refers to the willingness and availability of the parents to escort their children to the study centers.

Within the last years, digitalization has also shaped the field of medicine and many studies on eHealth and communication technology--based interventions for promoting physical activity (PA) show remarkable results ([@B22]). The new appealing possibility to transmit, conduct and control interventions from remote is also promising for studies in the field of patients with CHD. It is now possible to involve children with long distance to the study center to realize studies that otherwise would fail due to sample size. Currently children and adolescents grow up to be "digital natives" which are even more familiar in handling and executing app-based tasks, than dealing with paperwork. In addition, communication via social media platforms becomes more and more appropriate to monitor the study progress and maintain study compliance, instead of classic phone calls.

In patients with CHD, eHealth is largely unexplored with only one published study on physical exercise on aerobic fitness so far ([@B23], [@B24]). Therefore, we have launched a randomized controlled trial (RCT) that aims to improve functional outcome measures, primarily HRPF, in children and adolescents with CHD via a tailored web-based exercise/motor intervention over 24 weeks. That article describes the study protocol in detail.

Methods {#s2}
=======

Design and participants
-----------------------

The current study is planned as a randomized control trial (RCT) with a crossover design and the purpose to improve functional outcome measures in patients with CHD via a web-based exercise/motor intervention over 24 weeks. The treatment scheme and data collection is presented in Figure [1](#F1){ref-type="fig"}. According to the inclusion and exclusion criteria outlined in Table [1](#T1){ref-type="table"}, 70 children will be recruited and allocated randomly 1:1 in the two study arms after baseline testing. After 24 weeks, there will be a re-assessment of the clinical measurements.

![Study design and intervention scheme.](fped-06-00224-g0001){#F1}

###### 

Inclusion and exclusion criteria.

  **Inclusion criteria**                                                                                 **Exclusion criteria**
  ------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------
  Age 10--18 years old                                                                                   Severe arrhythmias
  CHD with moderate to complex severity according to the ACC criteria[^\*^](#TN1){ref-type="table-fn"}   Severe left heart failure
  Health-related physical fitness \< 50th percentile (healthy reference)                                 Chromosomal anomalies and/or genetic syndromes
  German speaking                                                                                        Severe physical and/or sensory impairments (hearing, visual, or psychomotor)
  Internet availability and an internet-capable device to use the intervention app                       Elective cardiac intervention within the next 6 months following enrollment
  Informed consent of parent/guardian as well as of the child                                            

*According to Warnes et al. ([@B25])*.

The accordance of the Declaration of Helsinki (revision 2008) and the Good Clinical Practice Guidelines is the basis of this upcoming study. The study protocol is already approved by the ethical board of the Technical University of Munich (project number: 130/17S). All children and their guardians will provide written informed consent. The trial is already registered at <https://ClinicalTrials.gov> (NCT03488797).

Intervention
------------

The motto of the exercise/motor intervention is "One Hour a Week, Brings Mobility, Power and Speed" which refers to the weekly training volume of 60 min. These 60 min are separated into 3 weekly sessions of 20 min each. The intervention is set up for 24 weeks (\~6 month), resulting in a total of 72 exercise sessions (3 sessions per week over 24 weeks) for each participant.

Each session comprises 20 child-oriented exercises with the focus to increase strength and flexibility. Exercises are executed for 30 s followed by a recovery period of 30 s. Each session starts with 3--4 warming-up exercises, followed by 10--12 strength and flexibility exercises, and ending with 3--4 cool down or stretching tasks.

All exercise sessions are continuous video clips transmitted to the participants via the web-based e-Learning platform Einstein (<https://einstein.costner.is>). The participant simply has to imitate the execution and follow some short advices. For a better orientation, a timer in the upper right corner displays the duration of exercise and the time of recovery. Beep signals indicate the last 3 s of the exercise and recovery period.

After each session, the screen will jump to a short online survey. Participant will give a quick report on perceived exertion (Borg scale) and feasibility of the actual session. The investigator can thereby monitor adherence rate and, in case of lacking compliance, intervene via email or telephone calls. The three video clips will be available for 1 week (Monday to Sunday) and the participant is free to choose when to train. At the end of a week all sessions will be erased from the account and replaced by new 3 sessions. That procedure will be repeated over the target 24 weeks.

Clinical measurements
---------------------

All of the clinical measurements at baseline, short term (after 24 weeks of intervention and control group) and long-term (48 weeks after baseline) follow-up (Figure [1](#F1){ref-type="fig"}) will be conducted in the outpatient clinic of the German heart center in Munich.

### Health related physical fitness (HRPF)

HRPF will be tested by five different tests of the FITNESSGRAM®([@B26]) test battery in standardized order. The tests will be supervised by an experienced sports exercise physiologist.

-   **Curl-Up**: Abdominal strength and muscular endurance

    Execution: Supine position, flexed knees with an angle of around 140° and feet placed on the ground. Arms stretched out beside the body. The upper body moves slowly toward the knees and afterwards back to the ground.

    Assessment: Score of valid curls-ups.

-   **Push-Ups**: Upper body strength and muscular endurance

    Execution: Prone position, with stretched back and legs. Arms straight under the shoulders pushing the body up and down.

    Assessment: Score of valid push-ups.

-   **Shoulder Stretch**: Upper arm and shoulder girdle flexibility

    Execution: Hands clenched to fists. Bring fists together as close as possible behind the back. Avoid hollow back.

    Assessment: Distance of the knuckles of the forefingers. Both sides.

-   ∙ **Sit and Reach**: Hamstring flexibility

    Execution: Siting position, one leg stretched against a box, toes stretched upright. Other leg flexed. Reaching to the toes or further with straight arms.

    Assessment: Negative or positive values in cm depending on the zero line of the box/toes. Both sides.

-   **Trunk Lift**: Trunk extensor strength and flexibility

    Execution: Lying outstretched in prone position. Arms tight to the body and hands under the thighs. Lifting upper body without bouncing while looking toward the ground.

    Assessment: Distance chin to ground in cm. Best of two trials.

Detailed information of the exercises and the test execution can be accessed from the online supplement of our recently published study in children with total cavopulmonary connection ([@B13], [@B17]).

### Measures of arterial stiffness

#### Functional: pulse wave velocity (pwv) and central systolic blood pressure (CSBP)

Measures of arterial stiffness involve pulse wave velocity (PWV) and central systolic blood pressure. Functional measures of arterial stiffness play a significant role in the development of cardiovascular disease and associations to physical activity have been outlined in adult and pediatric cohorts as well ([@B27], [@B28]).

Therefore, the automated, oscillometric Mobil-o-Graph (I.E.M GmbH, Stolberg, Germany) is used. The measurement will be performed at the left upper arm after resting in supine position for 5 min. Cuff size is adjusted for individual arm circumference. The inbuilt ARCSolver algorithm of the device uses a transfer function to calculate PWV and central systolic blood pressure based on the peripheral wave form ([@B29]). The device has shown good validity and applicability in several studies, even in patients with CHD ([@B12], [@B30], [@B31]).

#### Structural: carotid intima-media thickness (cIMT)

Carotid intima-media thickness (cIMT) is a marker for structural changes of the vessels and for early atherosclerosis. It is shown that physical activity in general is associated with favorable IMT outcomes in children and adolescents ([@B32], [@B33]).

cIMT will be measured using B-Mode ultrasound. To minimize inter- and intra-observer variability the guidelines of the Cardiovascular Prevention Working Group of the Association for European Paediatric Cardiology are followed ([@B34]).

The semi-automated GM-72P00A Cardiohealth Station from Panasonic (Yokohama, Japan) is used together with a linear probe of 9 MHz to assess cIMT at the arteria carotis communis. The measurements are conducted in supine position with patients head turned 45 degrees to the opposite of the examined side and the neck slightly tilted backwards. In the first step, the neck vessels were scanned for plaques in a cross-section, afterwards the common carotid artery was displayed in the longitudinal view.

Pictures are then taken of the cIMT on the far-wall, in the end-diastolic phase, \~1 cm proximal to the bifurcation in two angles on the left (210° and 240° degrees) and two angles on the right side (120° and 150° degrees).

### Health related quality of life (HRQoL)

The KINDL-R questionnaire is handed out to assess Health related Quality of Life (HRQoL). It is a common, international and well standardized questionnaire for evaluating children\'s HRQoL from a subjective perspective ([@B35]--[@B38]). It exists in three versions according to the different age groups. In this study, the KidKINDL for children aged 7--13 years and the KiddoKINDL for chidlren aged 14--17 years is used.

The questionnaire consists of 24 items that refer to the past week and is answered on a 5-point Likert scale (never, seldom, sometimes, often, and always). The scored items are then transferred to a total HRQoL score and to six subscales (physical, emotional, self-esteem, family, friends, everyday functioning). All subscales are graded on a scale from 0 to 100, whereby higher values reflect better HRQoL.

Enrollment
----------

The participants will perform the five motor tasks initially. Based on the test results of a reference cohort, LMS values were calculated according to Cole ([@B39]) using R-Studio (version 0.99.879, R-Studio Inc.) with the module extensions *gamlss* (version 3.4-8) and AGD (version 0.34). Children with CHD will be classified according to those established LMS values and z-scores displayed for every of the five tasks and HRPF z-score as the mean of the five tasks.

Participants are consecutive randomized and, when admitted to the intervention arm, start directly the week after screening for baseline characteristics with the exercise program. Every participant receives an anonymous account where 3 sessions will appear every week.

Endpoints
---------

### Primary endpoint

The primary endpoint criterion refers to an improvement of health-related physical fitness, assessed as the mean z-score of the five tests, 24 weeks (\~6 month) after intervention.

### Secondary endpoints

Secondary endpoints are as followed: Compliance (adherence) with the supervised web- and home-based intervention measured as participation rate in the training sessions (%).Improvement of Central/peripheral blood pressure after 24 weeks (\~6 month) after intervention.Improvement of Intima-media thickness after 24 weeks (\~6 month) after intervention.Improvement of health-related quality of life 24 weeks (\~6 month) after intervention.Improvement of pulse wave velocity 24 weeks (\~6 month) after intervention.

Sample size calculation
-----------------------

Sample size was calculated with G^\*^ (<http://www.gpower.hhu.de>) according to the primary endpoint criterion. According to our preceding cross-sectional study ([@B12], [@B13], [@B40]) a HRPF z-score of about −0.64 ± 0.9 (27th percentile) was averaged in the CHD children in comparison to the healthy reference. The study aims to improve HRPF to a value of 0.0 ± 1.0 (50th percentile) at the end of the intervention. With a power of 85% on a one-sided level of significance of 0.05 a sample size of 31 per group is necessary. Assuming a slight drop out of about 10% in total 70 children will be recruited and allocated randomly 1:1 in the two study arms.

Statistical methods
-------------------

Difference of the HRPF z-score for each participant will be compared between both study groups using an independent two-sample *t*-test (if normal distributed) or Mann--Whitney U-Test (if skewed). To calculate gender specific and group specific differences over time, repeated ANOVA measures (if normal distributed) or Friedman-test (if skewed) will be performed. In terms of drop-out an intention to threat analysis will be performed. Two-sided level of significance of 5% will be considered for this primary endpoint.

Discussion {#s3}
==========

The objective of this RCT is to determine the effect on HRPF and other functional outcome measures, as well as the compliance of a web-based exercise intervention in children with CHD.

Several studies in CHD have shown that participation in a physical exercise-training program is safe and improves fitness ([@B18], [@B41]). Unfortunately, those exercise interventions are underutilized in children with CHD and fitness, as the primary endpoint, is mostly just determined as an improvement in peak oxygen uptake while interest in other functional measures is rare. Indeed, peak oxygen uptake may be the most important prognostic parameter for survival in patients with CHD ([@B19]--[@B21]) but it is controversial whether that importance already exists in children with CHD. The idea behind is the changing landscape of older patients with CHD that will develop acquired cardiovascular disease, such as hypertension and hyperlipidemia ([@B42], [@B43]). From the perspective of primary prevention, it is therefore more important to shape PA behavior early in life that yield health benefits later in life. Motor skill development across the childhood has proven to influence children\'s PA behavior beneficially later in life in many ways ([@B44], [@B45]). Therefore, the objective of this study refers to HRPF and other functional outcomes instead of solely peak oxygen uptake.

Several studies already have investigated the feasibility and effectiveness of a home-based exercise intervention for young and adult people with CHD ([@B14], [@B18]). The utility of exercise interventions for this target group is unchallenged, but in 21 studies only 621 subjects, 30 per study, were included ([@B18]). Those small sample sizes very often lead to missing results and weak generalizability. Moreover, supervised training interventions are difficult to schedule and to conduct because of the low prevalence of patients with CHD.

To overcome those problems this study uses a web-based solution for two reasons. First, to include more patients in particular from remote areas and second, to deliver and monitor the intervention more effectively. The proposed training stimulus of 3 session of 20 min per week result in a relatively low real training volume of 30 min per week because the other 30 min are recovery time. Most of the studies mentioned in the comprehensive review ([@B18]) had longer durations for one training session and an overall higher workload per week but were conducted for only 12 weeks. Since this study takes twice as long we decided not to occupy the patient with intensive training. Instead it is assumed that less workload throughout the week leads to a better long-term compliance. That is also the reason why the patient is free in performing its 3 sessions per week instead of sticking to a fixed schedule.

The biggest challenge is the monitoring of the home-base intervention. Indeed 10 of the 21 studies did not report participation rate. Commonly in home-based intervention that is done by training logs and/or regular phone calls---a method that is inappropriate and especially uneconomical these days because they are not manageable outside a clinical study. With the electronic reporting and the possibility of tracking when training session were streamed it is much easier to follow compliance. In addition, automated messages can be sent to the patients to remind him/her of the execution and vice versa the supervisor when a training progress is missing. Nevertheless, it cannot entirely ruled out that the patients cheat in reporting. Consumer friendly wearable technology is a promising prospect in dealing with that issue but currently applications that are easy to use and connected to a central server are missing ([@B46]).

Web-based or eHealth PA interventions in patients with CHD are virtually not existent. Only the PReVaiL ([@B23], [@B24]) trial tried to assess benefits and harms of a tailored eHealth intervention with education and individual counseling in adolescents with CHD. Unfortunately, no change in oxygen uptake, PA and health-related quality of life occurred 52 weeks after the educational and motivational intervention. However, the most frustrating point was the low compliance to the intervention, which clearly outlined the vulnerability of those web-based approaches. Therefor our web-based intervention will contain exercise videos for a maximum of 24 weeks to minimize the number of drop-out. Further each exercise session consists of 20 different exercises that won\'t take more than 20 min. This means the amount of exercise is right at a level where changes in HRPF still can be expected but former inactive people aren\'t overstrained with an excessive exercise amount. Nevertheless, eHealth provides easy and wide reachability by low cost. Strategies have to be developed and evaluated to use this technique to maintain and improve the clinical care in this growing cohort of patients with CHD. This study aims to understand feasibility and compliance of those web-based studies.

Author contributions {#s4}
====================

MM, A-LH, LB, RO, PE, and JM were all involved in development of the study protocol. JM prepared the initial draft of the manuscript. MM and AH set up the database infrastructure for the intervention. All authors read, contributed to editing, and approved the final manuscript.

Conflict of interest statement
------------------------------

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The authors would like to thank the staff, and especially the nurses, of the outpatient apartment of the German Heart Centre for their dedicative support in this project.

This work was supported by the German Research Foundation (DFG) and the Technical University of Munich (TUM) in the framework of the Open Access Publishing Program.

**Funding.** This study is funded by an unrestricted grant from the Robert-Enke-Stiftung and the Fördergemeinschaft Deutsche Kinderherzzentren e.V.

CHD

:   congenital heart disease

cIMT

:   Carotid Intima-media Thickness

HRPF

:   heat-related physical fitness

HRQoL

:   Health related Quality of Life

PWV

:   pulse wave velocity

RCT

:   randomized controlled trial.

[^1]: Edited by: Tim Takken, University Medical Center Utrecht, Netherlands

[^2]: Reviewed by: Shahanawaz Syed, Mahatma Gandhi Mission Institute of Health Sciences, India; Daniel Rossignol, Rossignol Medical Center, United States

[^3]: This article was submitted to Children and Health, a section of the journal Frontiers in Pediatrics