Collaborative Care Interventions for Patients with Multimorbidity: Protocol for a Systematic Review and Meta-Analysis with Preliminary Results.

Collaborative care interventions have been proposed as a promising strategy for the management of patients with multimorbidity. This systematic review and meta-analysis aims to assess the effectiveness of collaborative care interventions for adult patients with multimorbidity. Furthermore, a meta-regression analysis is planned to determine if certain participant or intervention characteristics can explain variance in effect.

Machine Learning-Driven Prediction of Comorbidities and Mortality in Adults With Type 1 Diabetes.

BACKGROUND: Comorbidities such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) are major burdens of type 1 diabetes (T1D). Predicting people at high risk of developing comorbidities would enable early intervention. This study aimed to develop models incorporating socioeconomic status (SES) to predict CVD, DKD, and mortality in adults with T1D to improve early identification of comorbidities. METHODS: Nationwide Danish registry data were used. Logistic regression models were developed to predict the development of CVD, DKD, and mortality within five years of T1D diagnosis. Features included age, sex, personal income, and education. Performance was evaluated by five-fold cross-validation with area under the receiver operating characteristic curve (AUROC) and the precision-recall area under the curve (PR-AUC). The importance of SES was assessed from feature importance plots. RESULTS: Of the 6572 included adults (≥21 years) with T1D, 379 (6%) developed CVD, 668 (10%) developed DKD, and 921 (14%) died within the five-year follow-up. The AUROC (±SD) was 0.79 (±0.03) for CVD, 0.61 (±0.03) for DKD, and 0.87 (±0.01) for mortality. The PR-AUC was 0.18 (±0.01), 0.15 (±0.03), and 0.49 (±0.02), respectively. Based on feature importance plots, SES was the most important feature in the DKD model but had minimal impact on models for CVD and mortality. CONCLUSIONS: The developed models showed good performance for predicting CVD and mortality, suggesting they could help in the early identification of these outcomes in individuals with T1D. The importance of SES in individual prediction within diabetes remains uncertain.

Open Digital Health Workshops - A Model for Mutual Contact and Knowledge Exchange with the Local Community.

The increasing percentage of elderly in our society is challenging the health care system. To meet the challenge, we have implemented an experience-based master's programme in digital health care. The 3-yrs 90 ECTS programme consists of physical sessions of three days duration and weekly 2-3-hour digital lectures and bi-weekly supervisions. A main goal of the program has been to involve the students in relevant local and regional health problems as well as inviting health care personnel to participate in the planning of the study program, present relevant health problems and challenges and follow our open digital health workshops. In this way we have managed to create a stimulating learning environment for both students on further education and local and regional health care personnel.

Development of a Basal Insulin Titration System to Support Healthcare Providers in Treatment of People with Type 2 Diabetes: Preliminary Results.

The study aims to develop a system for insulin titration in type 2 diabetes to assist primary healthcare providers. Usability testing with end-users is ongoing.

Prediction of Poor Glycemic Control in Children with Type 1 Diabetes.

This study developed and validated a machine learning model for predicting glycemic control in children with type 1 diabetes at the time of diagnosis, revealing age at diagnosis as the most informative predictor.

Detailed Insights into Basal Insulin Adherence in People with Type 2 Diabetes Using a Data-Driven Assessment Method.

INTRODUCTION: Basal insulin non-adherence is a challenge in people with type 2 diabetes (T2D). METHODS: Using injection data recorded by a connected insulin pen, we employed a novel three-step methodology to assess three aspects of adherence (overall adherence, adherence distribution, and dose deviation) in individuals with insulin-treated T2D undergoing telemonitoring. RESULTS: Among participants, 52% were considered overall adherent. However, deviations from the recommended dose were observed in all participants, with increased and reduced doses being the predominant forms of non-adherence. CONCLUSIONS: Our study underscores the prevalence of basal insulin dosing irregularities in individuals with insulin-treated T2D undergoing telemonitoring.

Usability Evaluation of a Web-Based Remote Patient Monitoring Application: An Ongoing Study.

This study aims to discover problems and user experiences in a new released version of Sleepiz web application using heuristic evaluation and eye-tracking retrospective think-aloud performed by domain experts and end users. The web application is designed to support healthcare professionals in decision-making and monitoring of elderly people diagnosed with chronic respiratory diseases. Identification of usability problems and user experiences might contribute to improve the platform and will be reported to the developers.

Evaluating the Usability of a Telehealth System for People with COPD: A Cross Sectional Study.

Pulmonary Disease (COPD) exacerbations. However, the effect of telehealth for COPD remains uncertain, which may be due to a lack of attention to usability during the development of telehealth solutions. The aim was to evaluate the usability of a telehealth system for COPD using the Danish Telehealth Usability Questionnaire. A total of 96 people with COPD, who were already using a telehealth system consisting of weekly measurements of physiological parameters and symptom-related questionnaires, were included. The D-TUQ was used to assess the usability of the telehealth system. The overall experience with the usability of the telehealth system was mainly positive, but there was room for improvement.

Discordance Between Mealtimes Reported by Trial Participants with Type 2 Diabetes and Healthcare Professionals.

Healthy lifestyle behaviors are essential in the treatment of type 2 diabetes, and meal registration is therefore important. Manual meal registration is cumbersome and could be automated using continuous glucose monitoring (CGM). If such an algorithm is based on patient-reported meals, potential errors might be induced. Thus, the aim was to investigate potential errors in patient-reported mealtimes and the effect on automatic meal detection. Two healthcare professionals (HCPs) reported the mealtimes of the 18 included patients based on the patients' CGM data to assess the agreement between HCP- and patient-reported mealtimes. A developed meal detection algorithm based on detecting the post-prandial glucose response using cross-correlation was used to assess the impact of errors in patient-reported meals. The results showed poor disagreement between HCP- and patient-reported meals and that the meal detection algorithm had a moderately better performance on the HCP-reported meals. Therefore, the possibility of errors in patient-reported mealtimes should be considered in the development of meal detection algorithms. However, more research is needed to confirm the results of this study.

The Effectiveness of Collaborative Care Interventions for the Management of Patients With Multimorbidity: Protocol for a Systematic Review, Meta-Analysis, and Meta-Regression Analysis.

BACKGROUND: Collaborative care interventions have been proposed as a promising strategy to support patients with multimorbidity. Despite this, the effectiveness of collaborative care interventions requires further evaluation. Existing systematic reviews describing the effectiveness of collaborative care interventions in multimorbidity management tend to focus on specific interventions, patient subgroups, and settings. This necessitates a comprehensive review that will provide an overview of the effectiveness of collaborative care interventions for adult patients with multimorbidity. OBJECTIVE: This systematic review aims to systematically assess the effectiveness of collaborative care interventions in comparison to usual care concerning health-related quality of life (HRQoL), mental health, and mortality among adult patients with multimorbidity. METHODS: Randomized controlled trials evaluating collaborative care interventions designed for adult patients (18 years and older) with multimorbidity compared with usual care will be considered for inclusion in this review. HRQoL will be the primary outcome. Mortality and mental health outcomes such as rating scales for anxiety and depression will serve as secondary outcomes. The systematic search will be conducted in the CENTRAL, PubMed, CINAHL, and Embase databases. Additional reference and citation searches will be performed in Google Scholar, Web of Science, and Scopus. Data extraction will be comprehensive and include information about participant characteristics, study design, intervention details, and main outcomes. Included studies will be assessed for limitations according to the Cochrane Risk of Bias tool. Meta-analysis will be conducted to estimate the pooled effect size. Meta-regression or subgroup analysis will be undertaken to explore if certain factors can explain the variation in effect between studies, if feasible. The certainty of evidence will be evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. RESULTS: The preliminary literature search was performed on February 16, 2024, and yielded 5255 unique records. A follow-up search will be performed across all databases before submission. The findings will be presented in forest plots, a summary of findings table, and in narrative format. This systematic review is expected to be completed by late 2024. CONCLUSIONS: This review will provide an overview of pooled estimates of treatment effects across HRQoL, mental health, and mortality from randomized controlled trials evaluating collaborative care interventions for adults with multimorbidity. Furthermore, the intention is to clarify the participant, intervention, or study characteristics that may influence the effect of the interventions. This review is expected to provide valuable insights for researchers, clinicians, and other decision-makers about the effectiveness of collaborative care interventions targeting adult patients with multimorbidity. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42024512554; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=512554. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58296.

Intelligent Diabetes Telemonitoring for Patients on Insulin Therapy: A Randomized Controlled Trial Protocol.

Protocol for a three-arm randomized controlled trial investigating telemonitoring with decision support in insulin-treated people with type 2 diabetes.

Application of Machine Learning in Multimorbidity Research: Protocol for a Scoping Review.

BACKGROUND: Multimorbidity, defined as the coexistence of multiple chronic conditions, poses significant challenges to health care systems on a global scale. It is associated with increased mortality, reduced quality of life, and increased health care costs. The burden of multimorbidity is expected to worsen if no effective intervention is taken. Machine learning has the potential to assist in addressing these challenges since it offers advanced analysis and decision-making capabilities, such as disease prediction, treatment development, and clinical strategies. OBJECTIVE: This paper represents the protocol of a scoping review that aims to identify and explore the current literature concerning the use of machine learning for patients with multimorbidity. More precisely, the objective is to recognize various machine learning models, the patient groups involved, features considered, types of input data, the maturity of the machine learning algorithms, and the outcomes from these machine learning models. METHODS: The scoping review will be based on the guidelines of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). Five databases (PubMed, Embase, IEEE, Web of Science, and Scopus) are chosen to conduct a literature search. Two reviewers will independently screen the titles, abstracts, and full texts of identified studies based on predefined eligibility criteria. Covidence (Veritas Health Innovation Ltd) will be used as a tool for managing and screening papers. Only studies that examine more than 1 chronic disease or individuals with a single chronic condition at risk of developing another will be included in the scoping review. Data from the included studies will be collected using Microsoft Excel (Microsoft Corp). The focus of the data extraction will be on bibliographical information, objectives, study populations, types of input data, types of algorithm, performance, maturity of the algorithms, and outcome. RESULTS: The screening process will be presented in a PRISMA-ScR flow diagram. The findings of the scoping review will be conveyed through a narrative synthesis. Additionally, data extracted from the studies will be presented in more comprehensive formats, such as charts or tables. The results will be presented in a forthcoming scoping review, which will be published in a peer-reviewed journal. CONCLUSIONS: To our knowledge, this may be the first scoping review to investigate the use of machine learning in multimorbidity research. The goal of the scoping review is to summarize the field of literature on machine learning in patients with multiple chronic conditions, highlight different approaches, and potentially discover research gaps. The results will offer insights for future research within this field, contributing to developments that can enhance patient outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53761.

A telemonitoring intervention design for patients with poorly controlled type 2 diabetes: protocol for a feasibility study.

BACKGROUND: Maintaining optimal glycemic control in type 2 diabetes (T2D) is difficult. Telemedicine has the potential to support people with poorly regulated T2D in the achievement of glycemic control, especially if the telemedicine solution includes a telemonitoring component. However, the ideal telemonitoring design for people with T2D remains unclear. Therefore, the aim of this feasibility study is to evaluate the feasibility of two telemonitoring designs for people with non-insulin-dependent T2D with a goal of identifying the optimal telemonitoring intervention for a planned future large-scale randomized controlled trial. METHOD: This 3-month randomized feasibility study will be conducted in four municipalities in North Denmark starting in January 2024. There will be 15 participants from each municipality. Two different telemonitoring intervention designs will be tested. One intervention will include self-monitoring of blood glucose (SMBG) combined with sleep and mental health monitoring. The second intervention will include an identical setup but with the addition of blood pressure and activity monitoring. Two municipalities will be allocated to one intervention design, whereas the other two municipalities will be allocated to the second intervention design. Qualitative interviews with participants and clinicians will be conducted to gain insight into their experiences with and acceptance of the intervention designs and trial procedures (e.g., blood sampling and questionnaires). In addition, sources of differences in direct intervention costs between the two alternative interventions will be investigated. DISCUSSION: Telemonitoring has the potential to support people with diabetes in achieving glycemic control, but the existing evidence is inconsistent, and thus, the optimal design of interventions remains unclear. The results of this feasibility study are expected to produce relevant information about telemonitoring designs for people with T2D and help guide the design of future studies. A well-tested telemonitoring design is essential to ensure the quality of telemedicine initiatives, with goals of user acceptance and improved patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06134934 . Registered November 1, 2023. The feasibility trial has been approved (N-20230026) by the North Denmark Region Committee on Health Research Ethics (June 5, 2023).

Adherence to newer second-line oral antidiabetic drugs among people with type 2 diabetes-A systematic review.

The adherence to oral antidiabetic drugs (OADs) among people with type 2 diabetes (T2D) is suboptimal. However, new OADs have been marketed within the last 10 years. As these new drugs differ in mechanism of action, treatment complexity, and side effects, they may influence adherence. Thus, the aim of this study was to assess the adherence to newer second-line OADs, defined as drugs marketed in 2012-2022, among people with T2D. A systematic review was performed in CINAHL, Cochrane Trials, Embase, PubMed, PsycINFO, and Scopus. Articles were included if they were original research of adherence to newer second-line OADs and reported objective adherence quantification. The quality of the articles was assessed using JBI's critical appraisal tools. The overall findings were reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and summarized in a narrative synthesis. All seven included articles were European retrospective cohort studies investigating alogliptin, canagliflozin, dapagliflozin, empagliflozin, and unspecified types of SGLT2i. Treatment discontinuation and medication possession ratio (MPR) were the most frequently reported adherence quantification measures. Within the first 12 months of treatment, 29%-44% of subjects on SGLT2i discontinued the treatment. In terms of MPR, 61.7%-94.9% of subjects on either alogliptin, canagliflozin, dapagliflozin, empagliflozin or an unspecified SGLT2i were adherent. The two investigated adherence quantification measures, treatment discontinuation and MPR, suggest that adherence to the newer second-line OADs may be better than that of older OADs. However, a study directly comparing older and newer OADs should be done to verify this.

The Effectiveness of Digital Health Lifestyle Interventions on People With Prediabetes: Protocol for a Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: There has been an increasing interest in the use of digital health lifestyle interventions for people with prediabetes, as these interventions may offer a scalable approach to preventing type 2 diabetes. Previous systematic reviews on digital health lifestyle interventions for people with prediabetes had limitations, such as a narrow focus on certain types of interventions, a lack of statistical pooling, and no broader subgroup analysis of intervention characteristics. The identified limitations observed in previous systematic reviews substantiate the necessity of conducting a comprehensive review to address these gaps within the field. This will enable a comprehensive understanding of the effectiveness of digital health lifestyle interventions for people with prediabetes. OBJECTIVE: The objective of this systematic review, meta-analysis, and meta-regression is to systematically investigate the effectiveness of digital health lifestyle interventions on prediabetes-related outcomes in comparison with any comparator without a digital component among adults with prediabetes. METHODS: This systematic review will include randomized controlled trials that investigate the effectiveness of digital health lifestyle interventions on adults (aged 18 years or older) with prediabetes and compare the digital interventions with nondigital interventions. The primary outcome will be change in body weight (kg). Secondary outcomes include, among others, change in glycemic status, markers of cardiometabolic health, feasibility outcomes, and incidence of type 2 diabetes. Embase, PubMed, CINAHL, and CENTRAL (Cochrane Central Register of Controlled Trials) will be systematically searched. The data items to be extracted include study characteristics, participant characteristics, intervention characteristics, and relevant outcomes. To estimate the overall effect size, a meta-analysis will be conducted using the mean difference. Additionally, if feasible, meta-regression on study, intervention, and participant characteristics will be performed. The Cochrane risk of bias tool will be applied to assess study quality, and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of evidence. RESULTS: The results are projected to yield an overall estimate of the effectiveness of digital health lifestyle interventions on adults with prediabetes and elucidate the characteristics that contribute to their effectiveness. CONCLUSIONS: The insights gained from this study may help clarify the potential of digital health lifestyle interventions for people with prediabetes and guide the decision-making regarding future intervention components. TRIAL REGISTRATION: PROSPERO CRD42023426919; http://tinyurl.com/d3enrw9j. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50340.

Identification of individuals with diabetes who are eligible for continuous glucose monitoring forecasting.

BACKGROUND AND OBJECTIVES: Predicting glucose levels in individuals with diabetes offers potential improvements in glucose control. However, not all patients exhibit predictable glucose dynamics, which may lead to ineffective treatment strategies. We sought to investigate the efficacy of a 7-day blinded screening test in identifying diabetes patients suitable for glucose forecasting. METHODS: Participants with type 1 diabetes (T1D) were stratified into high and low initial error groups based on screening results (eligible and non-eligible). Long-term glucose predictions (30/60 min lead time) were evaluated among 334 individuals who underwent continuous glucose monitoring (CGM) over a total of 64,460,560 min. RESULTS: A strong correlation was observed between screening accuracy and long-term mean absolute relative difference (MARD) (0.661-0.736; p < 0.001), suggesting significant predictability between screening and long-term errors. Group analysis revealed a notable reduction in predictions falling within zone D of the Clark Error Grid by a factor of three and in zone C by a factor of two. CONCLUSIONS: The identification of eligible patients for glucose prediction through screening represents a practical and effective strategy. Implementation of this approach could lead to a decrease in adverse glucose predictions.

Prediction of pancreatic cancer risk in patients with new-onset diabetes using a machine learning approach based on routine biochemical parameters.

OBJECTIVE: To develop a machine-learning model that can predict the risk of pancreatic ductal adenocarcinoma (PDAC) in people with new-onset diabetes (NOD). METHODS: From a population-based sample of individuals with NOD aged >50 years, patients with pancreatic cancer-related diabetes (PCRD), defined as NOD followed by a PDAC diagnosis within 3 years, were included (n = 716). These PCRD patients were randomly matched in a 1:1 ratio with individuals having NOD. Data from Danish national health registries were used to develop a random forest model to distinguish PCRD from Type 2 diabetes. The model was based on age, gender, and parameters derived from feature engineering on trajectories of routine biochemical variables. Model performance was evaluated using receiver operating characteristic curves (ROC) and relative risk scores. RESULTS: The most discriminative model included 20 features and achieved a ROC-AUC of 0.78 (CI:0.75-0.83). Compared to the general NOD population, the relative risk for PCRD was 20-fold increase for the 1 % of patients predicted by the model to have the highest cancer risk (3-year cancer risk of 12 % and sensitivity of 20 %). Age was the most discriminative single feature, followed by the rate of change in haemoglobin A1c and the latest plasma triglyceride level. When the prediction model was restricted to patients with PDAC diagnosed six months after diabetes diagnosis, the ROC-AUC was 0.74 (CI:0.69-0.79). CONCLUSION: In a population-based setting, a machine-learning model utilising information on age, sex and trajectories of routine biochemical variables demonstrated good discriminative ability between PCRD and Type 2 diabetes.

A Three-Step Data-Driven Methodology to Assess Adherence to Basal Insulin Therapy in Patients With Insulin-Treated Type 2 Diabetes.

BACKGROUND: While health care providers (HCPs) are generally aware of the challenges concerning insulin adherence in adults with insulin-treated type 2 diabetes (T2D), data guiding identification of insulin nonadherence and understanding of injection patterns have been limited. Hence, the aim of this study was to examine detailed injection data and provide methods for assessing different aspects of basal insulin adherence. METHOD: Basal insulin data recorded by a connected insulin pen and prescribed doses were collected from 103 insulin-treated patients (aged ≥18 years) with T2D from an ongoing clinical trial (NCT04981808). We categorized the data and analyzed distributions of correct doses, increased doses, reduced doses, and missed doses to quantify adherence. We developed a three-step model evaluating three aspects of adherence (overall adherence, adherence distribution, and dose deviation) offering HCPs a comprehensive assessment approach. RESULTS: We used data from a connected insulin pen to exemplify the use of the three-step model to evaluate overall, adherence, adherence distribution, and dose deviation using patient cases. CONCLUSION: The methodology provides HCPs with detailed access to previously limited clinical data on insulin administration, making it possible to identify specific nonadherence behavior which will guide patient-HCP discussions and potentially provide valuable insights for tailoring the most appropriate forms of support.

Evaluation of a phosphate kinetics model in hemodialysis therapy-Assessment of the temporal robustness of model predictions.

In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a three-compartment phosphate kinetic model to individual patient data and assess the temporal robustness. Intradialytic phosphate samples were collected from the plasma and dialysate of 12 patients during two treatments (HD1 and HD2). 2-h postdialytic plasma samples were collected in four of the patients. First, the model was fitted to HD1 samples from each patient to estimate the mass transfer coefficients. Second, the best fitted model in each patient case was validated on HD2 samples. The best model fits were determined from the coefficient of determination (R2 ) values. When fitted to intradialytic samples only, the median (interquartile range) R2 values were 0.985 (0.959-0.997) and 0.992 (0.984-0.994) for HD1 and HD2, respectively. When fitted to both intra- and postdialytic samples, the results were 0.882 (0.838-0.929) and 0.963 (0.951-0.976) for HD1 and HD2, respectively. Eight patients demonstrated a higher R2 value for HD2 than for HD1. The model seems promising to predict individual plasma phosphate in hemodialysis patients. The results also show good temporal robustness of the model. Further modifications and validation on a larger sample are needed.

Quantification of insulin adherence in adults with insulin-treated type 2 diabetes: A systematic review.

AIMS: This systematic review aims to identify current methods used for the assessment of insulin adherence in adults with insulin-treated type 2 diabetes. The primary goal is to offer recommendations for clinical practice to improve quantification of adherence. METHODS: The review was conducted in accordance with PRISMA 2020 and registered at PROSPERO (CRD42022334134). PubMed, Embase, CINAHL, and PsycINFO were searched on 15 November 2022 and included three blocks: Type 2 diabetes, insulin, and adherence. We considered primary full-text studies describing an assessment method and a threshold for assessment of insulin adherence in adults with insulin-treated type 2 diabetes. RESULTS: A final sample of 50 studies were included. Identified methods fell into four categories: self-report, pharmacy claims, inulin count, and data from an insulin pen device. Commonly reported methods included: The Morisky Medication Adherence Scale, the (adjusted) Medication Possession Ratio, and the Proportions of Days Covered. A threshold of <80% was used to define non-adherence in nearly half of the studies. Yet, several thresholds were reported. CONCLUSIONS: Most available methods for assessing insulin adherence in adults with insulin-treated type 2 diabetes are severely limited in providing in-depth insights into timing, dosing size, injection patterns, and adherence behavior. However, recognizing diverse types of non-adherence is crucial, as they denote unique behavioral entities requiring targeted intervention. Employing insulin injection data (e.g., from a smart insulin pen cap) to underlie an assessment method is a potential new approach to objectively assess insulin timing and dosing adherence in adults with insulin-treated type 2 diabetes.