A Digitally Enabled Combined Lifestyle Intervention for Weight Loss: Pilot Study in a Dutch General Population Cohort.

BACKGROUND: Overweight and obesity rates among the general population of the Netherlands keep increasing. Combined lifestyle interventions (CLIs) focused on physical activity, nutrition, sleep, and stress management can be effective in reducing weight and improving health behaviors. Currently available CLIs for weight loss (CLI-WLs) in the Netherlands consist of face-to-face and community-based sessions, which face scalability challenges. A digitally enabled CLI-WL with digital and human components may provide a solution for this challenge; however, the feasibility of such an intervention has not yet been assessed in the Netherlands. OBJECTIVE: The aim of this study was two-fold: (1) to determine how weight and other secondary cardiometabolic outcomes (lipids and blood pressure) change over time in a Dutch population with overweight or obesity and cardiometabolic risk participating in a pilot digitally enabled CLI-WL and (2) to collect feedback from participants to guide the further development of future iterations of the intervention. METHODS: Participants followed a 16-week digitally enabled lifestyle coaching program rooted in the Fogg Behavior Model, focused on nutrition, physical activity, and other health behaviors, from January 2020 to December 2021. Participants could access the digital app to register and track health behaviors, weight, and anthropometrics data at any time. We retrospectively analyzed changes in weight, blood pressure, and lipids for remeasured users. Surveys and semistructured interviews were conducted to assess critical positive and improvement points reported by participants and health care professionals. RESULTS: Of the 420 participants evaluated at baseline, 53 participated in the pilot. Of these, 37 (70%) were classified as overweight and 16 (30%) had obesity. Mean weight loss of 4.2% occurred at a median of 10 months postintervention. The subpopulation with obesity (n=16) showed a 5.6% weight loss on average. Total cholesterol decreased by 10.2% and low-density lipoprotein cholesterol decreased by 12.9% on average. Systolic and diastolic blood pressure decreased by 3.5% and 7.5%, respectively. Participants identified the possibility of setting clear action plans to work toward and the multiple weekly touch points with coaches as two of the most positive and distinctive components of the digitally enabled intervention. Surveys and interviews demonstrated that the digital implementation of a CLI-WL is feasible and well-received by both participants and health care professionals. CONCLUSIONS: Albeit preliminary, these findings suggest that a behavioral lifestyle program with a digital component can achieve greater weight loss than reported for currently available offline CLI-WLs. Thus, a digitally enabled CLI-WL is feasible and may be a scalable alternative to offline CLI-WL programs. Evidence from future studies in a Dutch population may help elucidate the mechanisms behind the effectiveness of a digitally enabled CLI-WL.

Deep embedded clustering generalisability and adaptation for integrating mixed datatypes: two critical care cohorts.

We validated a Deep Embedded Clustering (DEC) model and its adaptation for integrating mixed datatypes (in this study, numerical and categorical variables). Deep Embedded Clustering (DEC) is a promising technique capable of managing extensive sets of variables and non-linear relationships. Nevertheless, DEC cannot adequately handle mixed datatypes. Therefore, we adapted DEC by replacing the autoencoder with an X-shaped variational autoencoder (XVAE) and optimising hyperparameters for cluster stability. We call this model "X-DEC". We compared DEC and X-DEC by reproducing a previous study that used DEC to identify clusters in a population of intensive care patients. We assessed internal validity based on cluster stability on the development dataset. Since generalisability of clustering models has insufficiently been validated on external populations, we assessed external validity by investigating cluster generalisability onto an external validation dataset. We concluded that both DEC and X-DEC resulted in clinically recognisable and generalisable clusters, but X-DEC produced much more stable clusters.

The necessity of incorporating non-genetic risk factors into polygenic risk score models.

The growing public interest in genetic risk scores for various health conditions can be harnessed to inspire preventive health action. However, current commercially available genetic risk scores can be deceiving as they do not consider other, easily attainable risk factors, such as sex, BMI, age, smoking habits, parental disease status and physical activity. Recent scientific literature shows that adding these factors can improve PGS based predictions significantly. However, implementation of existing PGS based models that also consider these factors requires reference data based on a specific genotyping chip, which is not always available. In this paper, we offer a method naïve to the genotyping chip used. We train these models using the UK Biobank data and test these externally in the Lifelines cohort. We show improved performance at identifying the 10% most at-risk individuals for type 2 diabetes (T2D) and coronary artery disease (CAD) by including common risk factors. Incidence in the highest risk group increases from 3.0- and 4.0-fold to 5.8 for T2D, when comparing the genetics-based model, common risk factor-based model and combined model, respectively. Similarly, we observe an increase from 2.4- and 3.0-fold to 4.7-fold risk for CAD. As such, we conclude that it is paramount that these additional variables are considered when reporting risk, unlike current practice with current available genetic tests.

Comparison of Machine Learning Models Including Preoperative, Intraoperative, and Postoperative Data and Mortality After Cardiac Surgery.

Importance: A variety of perioperative risk factors are associated with postoperative mortality risk. However, the relative contribution of routinely collected intraoperative clinical parameters to short-term and long-term mortality remains understudied. Objective: To examine the performance of multiple machine learning models with data from different perioperative periods to predict 30-day, 1-year, and 5-year mortality and investigate factors that contribute to these predictions. Design, Setting, and Participants: In this prognostic study using prospectively collected data, risk prediction models were developed for short-term and long-term mortality after cardiac surgery. Included participants were adult patients undergoing a first-time valve operation, coronary artery bypass grafting, or a combination of both between 1997 and 2017 in a single center, the University Medical Centre Groningen in the Netherlands. Mortality data were obtained in November 2017. Data analysis took place between February 2020 and August 2021. Exposure: Cardiac surgery. Main Outcomes and Measures: Postoperative mortality rates at 30 days, 1 year, and 5 years were the primary outcomes. The area under the receiver operating characteristic curve (AUROC) was used to assess discrimination. The contribution of all preoperative, intraoperative hemodynamic and temperature, and postoperative factors to mortality was investigated using Shapley additive explanations (SHAP) values. Results: Data from 9415 patients who underwent cardiac surgery (median [IQR] age, 68 [60-74] years; 2554 [27.1%] women) were included. Overall mortality rates at 30 days, 1 year, and 5 years were 268 patients (2.8%), 420 patients (4.5%), and 612 patients (6.5%), respectively. Models including preoperative, intraoperative, and postoperative data achieved AUROC values of 0.82 (95% CI, 0.78-0.86), 0.81 (95% CI, 0.77-0.85), and 0.80 (95% CI, 0.75-0.84) for 30-day, 1-year, and 5-year mortality, respectively. Models including only postoperative data performed similarly (30 days: 0.78 [95% CI, 0.73-0.82]; 1 year: 0.79 [95% CI, 0.74-0.83]; 5 years: 0.77 [95% CI, 0.73-0.82]). However, models based on all perioperative data provided less clinically usable predictions, with lower detection rates; for example, postoperative models identified a high-risk group with a 2.8-fold increase in risk for 5-year mortality (4.1 [95% CI, 3.3-5.1]) vs an increase of 11.3 (95% CI, 6.8-18.7) for the high-risk group identified by the full perioperative model. Postoperative markers associated with metabolic dysfunction and decreased kidney function were the main factors contributing to mortality risk. Conclusions and Relevance: This study found that the addition of continuous intraoperative hemodynamic and temperature data to postoperative data was not associated with improved machine learning-based identification of patients at increased risk of short-term and long-term mortality after cardiac operations.

Effect of a Digitally-Enabled, Preventive Health Program on Blood Pressure in an Adult, Dutch General Population Cohort: An Observational Pilot Study.

Worldwide, it is estimated that at least one in four adults suffers from hypertension, and this number is expected to increase as populations grow and age. Blood pressure (BP) possesses substantial heritability, but is also heavily modulated by lifestyle factors. As such, digital, lifestyle-based interventions are a promising alternative to standard care for hypertension prevention and management. In this study, we assessed the prevalence of elevated and high BP in a Dutch general population cohort undergoing a health screening, and observed the effects of a subsequent self-initiated, digitally-enabled lifestyle program on BP regulation. Baseline data were available for 348 participants, of which 56 had partaken in a BP-focused lifestyle program and got remeasured 10 months after the intervention. Participants with elevated SBP and DBP at baseline showed a mean decrease of 7.2 mmHg and 5.4 mmHg, respectively. Additionally, 70% and 72.5% of participants showed an improvement in systolic and diastolic BP at remeasurement. These improvements in BP are superior to those seen in other recent studies. The long-term sustainability and the efficacy of this and similar digital lifestyle interventions will need to be established in additional, larger studies.

A Pilot Study on the Prevalence of Micronutrient Imbalances in a Dutch General Population Cohort and the Effects of a Digital Lifestyle Program.

Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study, we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults and evaluated the effect of a digital lifestyle program on the nutritional status and nutrition health behaviors of these individuals. A micronutrient panel was measured in 348 participants, alongside a dietary assessment. One hundred users subsequently underwent a remeasurement. We identified at least one nutritional imbalance in 301 individuals (86.5%). A total of 80% improved and normalized B6, 67% improved folate, 70% improved B12, and 86% improved vitamin D. Iron abnormalities were corrected in 75% of the participants. In conclusion, this study found that micronutrient deficiencies of easily obtainable vitamins through diet or supplementation such as B vitamins and vitamin D were more prevalent than expected in a Dutch population. This can partly be explained by insufficient consumption of food groups rich in B vitamins. Our preliminary results in those remeasured after a digitally enabled lifestyle intervention show these imbalances can be corrected with adequate behavioral support complemented with supplementation where needed.

Changes in Blood Lipid Levels After a Digitally Enabled Cardiometabolic Preventive Health Program: Pre-Post Study in an Adult Dutch General Population Cohort.

BACKGROUND: Despite widespread education, many individuals fail to follow basic health behaviors such as consuming a healthy diet and exercising. Positive changes in lifestyle habits are associated with improvements in multiple cardiometabolic health risk factors, including lipid levels. Digital lifestyle interventions have been suggested as a viable complement or potential alternative to conventional health behavior change strategies. However, the benefit of digital preventive interventions for lipid levels in a preventive health context remains unclear. OBJECTIVE: This observational study aimed to determine how the levels of lipids, namely total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and triglycerides, changed over time in a Dutch general population cohort undergoing a digital preventive health program. Moreover, we looked to establish associations between lifestyle factors at baseline and lipid levels. METHODS: We included 348 adults from the Dutch general population who underwent a digitally enabled preventive health program at Ancora Health between January 2020 and October 2021. Upon enrollment, participants underwent a baseline assessment involving a comprehensive lifestyle questionnaire, a blood biochemistry panel, physical measurements, and cardiopulmonary fitness measurements. Thereafter, users underwent a lifestyle coaching program and could access the digital application to register and track health behaviors, weight, and anthropometric data at any time. Lipid levels were categorized as normal, elevated, high, and clinical dyslipidemia according to accepted international standards. If at least one lipid marker was high or HDL was low, participants received specific coaching and advice for cardiometabolic health. We retrospectively analyzed the mean and percentage changes in lipid markers in users who were remeasured after a cardiometabolic health-focused intervention, and studied the association between baseline user lifestyle characteristics and having normal lipid levels. RESULTS: In our cohort, 199 (57.2%) participants had dyslipidemia at baseline, of which 104 participants were advised to follow a cardiometabolic health-focused intervention. Eating more amounts of favorable food groups and being more active were associated with normal lipid profiles. Among the participants who underwent remeasurement 9 months after intervention completion, 57% (17/30), 61% (19/31), 56% (15/27), 82% (9/11), and 100% (8/8) showed improvements at remeasurement for total, LDL, HDL, and non-HDL cholesterol, and triglycerides, respectively. Moreover, between 35.3% and 77.8% showed a return to normal levels. In those with high lipid levels at baseline, total cholesterol decreased by 0.5 mmol/L (7.5%), LDL cholesterol decreased by 0.39 mmol/L (10.0%), non-HDL cholesterol decreased by 0.44 mmol/L (8.3%), triglycerides decreased by 0.97 mmol/L (32.0%), and HDL increased by 0.17 mmol/L (15.6%), after the intervention. CONCLUSIONS: A cardiometabolic screening program in a general population cohort identified a significant portion of individuals with subclinical and clinical lipid levels. Individuals who, after screening, actively engaged in a cardiometabolic health-focused lifestyle program improved their lipid levels.

Development and Validation of Decision Rules Models to Stratify Coronary Artery Disease, Diabetes, and Hypertension Risk in Preventive Care: Cohort Study of Returning UK Biobank Participants.

Many predictive models exist that predict risk of common cardiometabolic conditions. However, a vast majority of these models do not include genetic risk scores and do not distinguish between clinical risk requiring medical or pharmacological interventions and pre-clinical risk, where lifestyle interventions could be first-choice therapy. In this study, we developed, validated, and compared the performance of three decision rule algorithms including biomarkers, physical measurements, and genetic risk scores for incident coronary artery disease (CAD), diabetes (T2D), and hypertension against commonly used clinical risk scores in 60,782 UK Biobank participants. The rules models were tested for an association with incident CAD, T2D, and hypertension, and hazard ratios (with 95% confidence interval) were calculated from survival models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), and Net Reclassification Index (NRI). The higher risk group in the decision rules model had a 40-, 40.9-, and 21.6-fold increased risk of CAD, T2D, and hypertension, respectively (p < 0.001 for all). Risk increased significantly between the three strata for all three conditions (p < 0.05). Based on genetic risk alone, we identified not only a high-risk group, but also a group at elevated risk for all health conditions. These decision rule models comprising blood biomarkers, physical measurements, and polygenic risk scores moderately improve commonly used clinical risk scores at identifying individuals likely to benefit from lifestyle intervention for three of the most common lifestyle-related chronic health conditions. Their utility as part of digital data or digital therapeutics platforms to support the implementation of lifestyle interventions in preventive and primary care should be further validated.

Identifying and characterizing high-risk clusters in a heterogeneous ICU population with deep embedded clustering.

Critically ill patients constitute a highly heterogeneous population, with seemingly distinct patients having similar outcomes, and patients with the same admission diagnosis having opposite clinical trajectories. We aimed to develop a machine learning methodology that identifies and provides better characterization of patient clusters at high risk of mortality and kidney injury. We analysed prospectively collected data including co-morbidities, clinical examination, and laboratory parameters from a minimally-selected population of 743 patients admitted to the ICU of a Dutch hospital between 2015 and 2017. We compared four clustering methodologies and trained a classifier to predict and validate cluster membership. The contribution of different variables to the predicted cluster membership was assessed using SHapley Additive exPlanations values. We found that deep embedded clustering yielded better results compared to the traditional clustering algorithms. The best cluster configuration was achieved for 6 clusters. All clusters were clinically recognizable, and differed in in-ICU, 30-day, and 90-day mortality, as well as incidence of acute kidney injury. We identified two high mortality risk clusters with at least 60%, 40%, and 30% increased. ICU, 30-day and 90-day mortality, and a low risk cluster with 25-56% lower mortality risk. This machine learning methodology combining deep embedded clustering and variable importance analysis, which we made publicly available, is a possible solution to challenges previously encountered by clustering analyses in heterogeneous patient populations and may help improve the characterization of risk groups in critical care.

Cognitive biases, environmental, patient and personal factors associated with critical care decision making: A scoping review.

PURPOSE: Cognitive biases and factors affecting decision making in critical care can potentially lead to life-threatening errors. We aimed to examine the existing evidence on the influence of cognitive biases and factors on decision making in critical care. MATERIALS AND METHODS: We conducted a scoping review by searching MEDLINE for articles from 2004 to November 2020. We included studies conducted in physicians that described cognitive biases or factors associated with decision making. During the study process we decided on the method to summarize the evidence, and based on the obtained studies a descriptive summary of findings was the best fit. RESULTS: Thirty heterogenous studies were included. Four main biases or factors were observed, e.g. cognitive biases, personal factors, environmental factors, and patient factors. Six (20%) studies reported biases associated with decision making comprising omission-, status quo-, implicit-, explicit-, outcome-, and overconfidence bias. Nineteen (63%) studies described personal factors, twenty-two (73%) studies described environmental factors, and sixteen (53%) studies described patient factors. CONCLUSIONS: The current evidence on cognitive biases and factors is heterogenous, but shows they influence clinical decision. Future studies should investigate the prevalence of cognitive biases and factors in clinical practice and their impact on clinical outcomes.

Ensemble machine learning prediction and variable importance analysis of 5-year mortality after cardiac valve and CABG operations.

Despite having a similar post-operative complication profile, cardiac valve operations are associated with a higher mortality rate compared to coronary artery bypass grafting (CABG) operations. For long-term mortality, few predictors are known. In this study, we applied an ensemble machine learning (ML) algorithm to 88 routinely collected peri-operative variables to predict 5-year mortality after different types of cardiac operations. The Super Learner algorithm was trained using prospectively collected peri-operative data from 8241 patients who underwent cardiac valve, CABG and combined operations. Model performance and calibration were determined for all models, and variable importance analysis was conducted for all peri-operative parameters. Results showed that the predictive accuracy was the highest for solitary mitral (0.846 [95% CI 0.812-0.880]) and solitary aortic (0.838 [0.813-0.864]) valve operations, confirming that ensemble ML using routine data collected perioperatively can predict 5-year mortality after cardiac operations with high accuracy. Additionally, post-operative urea was identified as a novel and strong predictor of mortality for several types of operation, having a seemingly additive effect to better known risk factors such as age and postoperative creatinine.

Mortality prediction models in the adult critically ill: A scoping review.

BACKGROUND: Mortality prediction models are applied in the intensive care unit (ICU) to stratify patients into different risk categories and to facilitate benchmarking. To ensure that the correct prediction models are applied for these purposes, the best performing models must be identified. As a first step, we aimed to establish a systematic review of mortality prediction models in critically ill patients. METHODS: Mortality prediction models were searched in four databases using the following criteria: developed for use in adult ICU patients in high-income countries, with mortality as primary or secondary outcome. Characteristics and performance measures of the models were summarized. Performance was presented in terms of discrimination, calibration and overall performance measures presented in the original publication. RESULTS: In total, 43 mortality prediction models were included in the final analysis. In all, 15 models were only internally validated (35%), 13 externally (30%) and 10 (23%) were both internally and externally validated by the original researchers. Discrimination was assessed in 42 models (98%). Commonly used calibration measures were the Hosmer-Lemeshow test (60%) and the calibration plot (28%). Calibration was not assessed in 11 models (26%). Overall performance was assessed in the Brier score (19%) and the Nagelkerke's R2 (4.7%). CONCLUSIONS: Mortality prediction models have varying methodology, and validation and performance of individual models differ. External validation by the original researchers is often lacking and head-to-head comparisons are urgently needed to identify the best performing mortality prediction models for guiding clinical care and research in different settings and populations.

A Bayesian Network Analysis of the Diagnostic Process and Its Accuracy to Determine How Clinicians Estimate Cardiac Function in Critically Ill Patients: Prospective Observational Cohort Study.

BACKGROUND: Hemodynamic assessment of critically ill patients is a challenging endeavor, and advanced monitoring techniques are often required to guide treatment choices. Given the technical complexity and occasional unavailability of these techniques, estimation of cardiac function based on clinical examination is valuable for critical care physicians to diagnose circulatory shock. Yet, the lack of knowledge on how to best conduct and teach the clinical examination to estimate cardiac function has reduced its accuracy to almost that of "flipping a coin." OBJECTIVE: The aim of this study was to investigate the decision-making process underlying estimates of cardiac function of patients acutely admitted to the intensive care unit (ICU) based on current standardized clinical examination using Bayesian methods. METHODS: Patient data were collected as part of the Simple Intensive Care Studies-I (SICS-I) prospective cohort study. All adult patients consecutively admitted to the ICU with an expected stay longer than 24 hours were included, for whom clinical examination was conducted and cardiac function was estimated. Using these data, first, the probabilistic dependencies between the examiners' estimates and the set of clinically measured variables upon which these rely were analyzed using a Bayesian network. Second, the accuracy of cardiac function estimates was assessed by comparison to the cardiac index values measured by critical care ultrasonography. RESULTS: A total of 1075 patients were included, of which 783 patients had validated cardiac index measurements. A Bayesian network analysis identified two clinical variables upon which cardiac function estimate is conditionally dependent, namely, noradrenaline administration and presence of delayed capillary refill time or mottling. When the patient received noradrenaline, the probability of cardiac function being estimated as reasonable or good P(ER,G) was lower, irrespective of whether the patient was mechanically ventilated (P[ER,G|ventilation, noradrenaline]=0.63, P[ER,G|ventilation, no noradrenaline]=0.91, P[ER,G|no ventilation, noradrenaline]=0.67, P[ER,G|no ventilation, no noradrenaline]=0.93). The same trend was found for capillary refill time or mottling. Sensitivity of estimating a low cardiac index was 26% and 39% and specificity was 83% and 74% for students and physicians, respectively. Positive and negative likelihood ratios were 1.53 (95% CI 1.19-1.97) and 0.87 (95% CI 0.80-0.95), respectively, overall. CONCLUSIONS: The conditional dependencies between clinical variables and the cardiac function estimates resulted in a network consistent with known physiological relations. Conditional probability queries allow for multiple clinical scenarios to be recreated, which provide insight into the possible thought process underlying the examiners' cardiac function estimates. This information can help develop interactive digital training tools for students and physicians and contribute toward the goal of further improving the diagnostic accuracy of clinical examination in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02912624; https://clinicaltrials.gov/ct2/show/NCT02912624.

Observational Study Protocol for Repeated Clinical Examination and Critical Care Ultrasonography Within the Simple Intensive Care Studies.

Longitudinal evaluations of critically ill patients by combinations of clinical examination, biochemical analysis and critical care ultrasonography (CCUS) may detect adverse events of interventions such as fluid overload at an early stage. The Simple Intensive Care Studies (SICS) is a research line that focuses on the prognostic and diagnostic value of combinations of clinical variables. The SICS-I specifically focused on the use of clinical variables obtained within 24 h of acute admission for prediction of cardiac output (CO) and mortality. Its sequel, SICS-II, focuses on repeated evaluations during ICU admission. The first clinical examination by trained researchers is performed within 3 h after admission consisting of physical examination and educated guessing. The second clinical examination is performed within 24 h after admission and includes physical examination and educated guessing, biochemical analysis and CCUS assessments of heart, lungs, inferior vena cava (IVC) and kidney. This evaluation is repeated at days 3 and 5 after admission. CCUS images are validated by an independent expert, and all data is registered in an online secured database. Follow-up at 90 days includes registration of complications and survival status according to patient's medical charts and the municipal person registry. The primary focus of SICS-II is the association between venous congestion and organ dysfunction. The purpose of publishing this protocol is to provide details on the structure and methods of this on-going prospective observational cohort study allowing answering multiple research questions. The design of the data collection of combined clinical examination and CCUS assessments in critically ill patients are explicated. The SICS-II is open for other centers to participate and is open for other research questions that can be answered with our data.