Open research questions in Chronic Disease Management Strategies

What the literature leaves open

• The complexity of modelling physical comorbidity burden and mortality in people with SMI. The need to account for missing baseline data and potential biases in the study. The challenge of identifying distinct trajectory groups and their associated mortality risks using joint latent class modelling.

  Trajectories of physical comorbidity burden and all-cause mortality in people with severe mental illness: joint latent class modelling study with up to 10 years of follow-up · 2026 · DOI

• Further research is needed to understand the underlying causes of the mortality gap in people with SMI, - Studies should investigate the effectiveness of interventions to reduce physical multimorbidity in people with SMI, - Research should examine the impact of socioeconomic deprivation on health outcomes in people with SMI

  Trajectories of physical comorbidity burden and all-cause mortality in people with severe mental illness: joint latent class modelling study with up to 10 years of follow-up · 2026 · DOI

• Evaluation of interventions to improve mortality and life expectancy in people receiving mental healthcare, - Investigation of the role of comorbid conditions in excess mortality, - Monitoring of the situation to determine if the mortality gap is persisting or widening

  Mortality and life expectancy in people receiving mental healthcare without a diagnosis: South London electronic health records linkage study · 2026 · DOI

• The study faced challenges in replicating the indices due to lack of data on certain diseases and conditions. The severity of diabetes was not available in the dataset. The study had to map the original index definitions to the Rotterdam Study data.

  Counting co-occurring diseases to predict mortality is as accurate as multimorbidity indices: an external validation study · 2026 · DOI

• Assessing risk and pathways of disease transmission, - Intervention and prevention strategies based on the d factor, - Further exploration of the relationship between lifestyle and the d factor

  Large-scale evidence of a general disease (‘d’) factor accounting for both mental and physical health disorders in different age groups · 2025 · DOI

• The study identifies a gap in the literature by investigating the presence of a general disease factor across different age groups. Prior research has focused on specific mental and physical factors in different age groups, but not on a general disease factor.

  Large-scale evidence of a general disease (‘d’) factor accounting for both mental and physical health disorders in different age groups · 2025 · DOI

• The role of the HbA1c/HDL-C ratio in predicting cardiometabolic multimorbidity remains unclear. The combined effect of the HbA1c/HDL-C ratio and depression on cardiometabolic multimorbidity risk is not well understood.

  Association of HbA1c/HDL-C ratio and depression with cardiometabolic multimorbidity in middle-aged and older adults: a nationwide prospective cohort study · 2025 · DOI

• The study faces the challenge of identifying distinct subgroups of depression trajectories among middle-aged and older Chinese individuals with chronic diseases. The research needs to determine the significant factors affecting trajectory grouping. The study requires the use of appropriate statistical models to analyze the data.

  Identifying the subgroups of depression trajectories among the middle-aged and older Chinese individuals with chronic diseases: an 8-year follow-up study based on CHARLS · 2024 · DOI

• Investigate the relationship between health insurance status and depression trajectory. Investigate the relationship between drinking status and depression trajectory. Investigate the relationship between physical activity and depression trajectory. Replicate the study using different populations or datasets.

  Identifying the subgroups of depression trajectories among the middle-aged and older Chinese individuals with chronic diseases: an 8-year follow-up study based on CHARLS · 2024 · DOI

• Limited studies have explored the association between disability and multimorbidity. There is a need to understand the association between disability and multimorbidity in India's older adult population.

  Understanding the association of disability with multimorbidity, and healthcare utilization in India’s older adult population: insights from cross-sectional evidence of SAGE-2 · 2024 · DOI

• Small number of participants with comorbid overweight-depression did not provide enough statistical power, - Missing data in the study population, - Limited to a British birth cohort

  Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort · 2024 · DOI

• Investigating the mechanisms between ACEs and comorbid overweight-depression, - Examining the impact of ACEs on other types of multimorbidity, - Studying the effects of intervention strategies on ACEs and comorbidities

  Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort · 2024 · DOI

• Further research is needed to evaluate the performance of multimorbidity indices in different populations and settings. Research should focus on developing more accurate and reliable methods for predicting mortality and other health outcomes in patients with multimorbidity. The development of new multimorbidity indices that incorporate additional variables, such as lifestyle factors and disease severity, may be warranted.

  Counting co-occurring diseases to predict mortality is as accurate as multimorbidity indices: an external validation study · 2026 · DOI

• However, it remains unclear whether this concept effectively identifies patients with greater complexity of care needs.

  Treatment burden in complex versus simple multimorbidity: nationwide cross-sectional study in Japan · 2026 · DOI

• BackgroundAmenable mortality, deaths preventable through timely and effective healthcare, is a widely used indicator of health system performance, yet evidence is lacking on its individual-level determinants in Brazil.

  Amenable Mortality Among Older Brazilians: Evidence From the Brazilian Longitudinal Study of Aging (ELSI-Brazil) · 2026 · DOI

• ABSTRACT While the association between depressive symptoms and cardiometabolic disease is well established, the relationships among depressive symptoms, sleep disturbance, and cardiometabolic multimorbidity (CMM) in adults with arthritis remain insufficiently understood.

  Depressive Symptoms, sleep Disturbance, and Cardiometabolic Multimorbidity Among Adults With Arthritis: A Cross‐Sectional Analysis of NHANES 2013–2020 · 2026 · DOI

• Sleep disturbance may represent an important co‐occurring factor and warrants further investigation in prospective studies.

  Depressive Symptoms, sleep Disturbance, and Cardiometabolic Multimorbidity Among Adults With Arthritis: A Cross‐Sectional Analysis of NHANES 2013–2020 · 2026 · DOI

• BACKGROUND: Multimorbidity is a major determinant of older adults’ functioning, yet its long-term pathways and underlying mechanisms remain insufficiently understood.

  Multimorbidity and functioning disparities in retired older adults: longitudinal trajectories, disease clusters, and mediating mechanisms · 2026 · DOI

• However, research exploring the complexities of living with these conditions are scarce.

  Living with a multimorbidity. A qualitative study on the personal perspectives of individuals with type 2 diabetes and cardiovascular disease · 2025 · DOI

• BACKGROUND: Few studies have explored the impact of multimorbidity patterns on premature mortality.

  Multimorbidity patterns and premature mortality in a prospective cohort: effect modifications by socioeconomic status and healthy lifestyles · 2025 · DOI

• However, the role of the glycosylated hemoglobin A1c to high-density lipoprotein cholesterol ratio (HbA1c/HDL-C) in predicting CMM remains unclear.

  Association of HbA1c/HDL-C ratio and depression with cardiometabolic multimorbidity in middle-aged and older adults: a nationwide prospective cohort study · 2025 · DOI

• Background: The triglyceride-glucose (TyG) index is a recognized marker of insulin resistance, yet its role in the dynamic progression from cardiovascular disease (CVD) to cardiovascular multimorbidity (CVM) remains unclear.

  Triglyceride-glucose index as a predictor of cardiovascular multimorbidity: a prospective cohort study · 2025 · DOI

• Exercise therapy and self-management support are promising interventions, but their effect has not been evaluated.

  Exercise therapy and self-management support for individuals with multimorbidity: a randomized and controlled trial · 2025 · DOI

• This review emphasizes the important role of caregivers in the transition from hospital to home, addressing a significant gap in the literature.

  Transitional Care Interventions in Improving Patient and Caregiver Outcomes After Discharge: A Scoping Review · 2025 · DOI

• Understanding how multimorbidity patterns contribute to depression risk and identifying high-risk subgroups through integrated statistical and machine learning approaches remain underexplored, limiting targeted prevention strategies.

  Multimorbidity Patterns and Depression: Bridging Epidemiological Associations with Predictive Analytics for Risk Stratification · 2025 · DOI

Most-cited papers in Chronic Disease Management Strategies

• Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 · The Lancet · 2018 · 11,068 citations
• Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 · The Lancet · 2012 · 6,836 citations
• Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 · The Lancet · 2012 · 6,651 citations
• Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 · The Lancet · 2017 · 6,214 citations
• Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study · The Lancet · 2012 · 5,855 citations
• Updating and Validating the Charlson Comorbidity Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 Countries · American Journal of Epidemiology · 2011 · 5,279 citations
• Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 · The Lancet · 2015 · 5,026 citations
• Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population · American Journal of Epidemiology · 2017 · 3,987 citations
• The Functioning and Well-being of Depressed Patients · JAMA · 1989 · 2,647 citations
• Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 · The Lancet · 2018 · 2,550 citations

Most recent work

• Shared and specific blood biomarkers for multimorbidity · Nature Medicine · 2026
• Association between the CHG index and cardiometabolic multimorbidity: a nationwide prospective cohort and multi-community cross-sectional study · Frontiers in Nutrition · 2026
• Ten-year population-based assessment of multimorbidity burden progression in a regional cohort of 5.5 million adults · npj Digital Medicine · 2026
• Patterns of Children With Complex Chronic Conditions: A Latent Class Analysis · PEDIATRICS · 2026
• Interventions for the prevention and management of cardiometabolic multiple long-term conditions · The Lancet · 2026
• Epidemiology of cardiometabolic multiple long-term conditions · The Lancet · 2026
• Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes · JAMA · 2026
• Multimorbidity and suicidality among military veterans: a scoping review · Psychiatry Research · 2026
• Saving Healthcare Costs in the Real-World: Implementation of CAPABLE in Population-Based Care · Journal of Applied Gerontology · 2026
• The economic cost of outpatient primary care of adults with multimorbidity (HIV, diabetes, and hypertension) in rural South Africa · Health Policy and Planning · 2026

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