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Multimorbidity Development and Evolution: Clinical Implications

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Epidemiology & Public Health".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 35462

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Special Issue Editors

Dr. Davide Liborio Vetrano

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Guest Editor

Postdoctoral Fellow at the Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Interests: multimorbidity development; prognosis in older adults; frailty and functional decline in aging; multidimensional assessment of health in older people

Dr. Amaia Calderón-Larrañaga

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Guest Editor

Assistant Professor at the Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Interests: multimorbidity development; prognosis in older adults; frailty and functional decline in aging; multidimensional assessment of health in older people

Special Issue Information

Dear Colleagues,

Research on multimorbidity is regaining ground more than two decades after its origin. The growing number of individuals suffering from multiple chronic conditions undeniably challenges clinicians and healthcare systems, for whom targeted evidence-based guidelines and effective integrated care models are still lacking. Moreover, the significant knowledge gaps concerning the life-long risk factors of multimorbidity hinder the implementation of primary and secondary prevention strategies. Finally, the complex and heterogeneous nature of multimorbid patients is at the core of an endless number of clinical phenotypes, hampering any attempt to reliably predict negative health-related events.

Lately, the adoption of new operationalization models, the implementation of powerful statistical approaches, and the availability of longitudinal, comprehensive population-based data, have paved the way for a new generation of promising studies. The recognition of the clinical value of multimorbidity patterns and the biological relevance of measuring the speed of disease accumulation over time reflect recent trends to uncover the biological basis of multimorbidity, and to translate these findings into better prevention, treatment and prognosis of patients with multimorbidity.

Considering your expertise in the field, we would like to kindly invite you to contribute with an original paper or a literature review to the Special Issue of the Journal of Clinical Medicine, titled “Multimorbidity Development and Evolution: Clinical Implications.”

The articles in this collection are expected to cover the following areas:

Life-long psychosocial, behavioral and environmental risk factors for the development of multimorbidity.
Mechanisms and biomarker identification to improve the prevention, management and prognosis of older individuals with multimorbidity.
Relationship between multimorbidity, frailty, physical and cognitive function, and their synergistic effects on health outcomes.
Care-related factors, such as hospitalizations or drug-related problems, either resulting from or leading to multimorbidity.

We are looking forward to receiving your contribution.

Dr. Davide Liborio Vetrano
Dr. Amaia Calderón-Larrañaga
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

Multimorbidity
Chronic disease
Personalized medicine
Patient-centered care
Biomarkers
Frailty
Drug-related problems
Prognosis
Aging

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

2 pages, 195 KiB

Open AccessEditorial

Special Issue—“Multimorbidity Development and Evolution: Clinical Implications”

by Alberto Zucchelli, Amaia Calderón-Larrañaga and Davide Liborio Vetrano

J. Clin. Med. 2021, 10(16), 3450; https://doi.org/10.3390/jcm10163450 - 4 Aug 2021

Viewed by 1458

Abstract

Multimorbidity, the co-existence of multiple chronic diseases in the same individual, is not only extremely common in older persons but is also strongly associated with several poor health outcomes [...] Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

Research

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17 pages, 1261 KiB

Open AccessArticle

Assessing the Impact of Multi-Morbidity and Related Constructs on Patient Reported Safety in Primary Care: Generalized Structural Equation Modelling of Observational Data

by Ignacio Ricci-Cabello, Aina María Yañez-Juan, Maria A. Fiol-deRoque, Alfonso Leiva, Joan Llobera Canaves, Fabrice B. R. Parmentier and Jose M. Valderas

J. Clin. Med. 2021, 10(8), 1782; https://doi.org/10.3390/jcm10081782 - 20 Apr 2021

Cited by 2 | Viewed by 2989

Abstract

We aimed to examine the complex relationships between patient safety processes and outcomes and multimorbidity using a comprehensive set of constructs: multimorbidity, polypharmacy, discordant comorbidity (diseases not sharing either pathogenesis nor management), morbidity burden and patient complexity. We used cross-sectional data from 4782 patients in 69 primary care centres in Spain. We constructed generalized structural equation models to examine the associations between multimorbidity constructs and patient-reported patient safety (PREOS-PC questionnaire). These associations were modelled through direct and indirect (mediated by increased interactions with healthcare) pathways. For women, a consistent association between higher levels of the multimorbidity constructs and lower levels of patient safety was observed via either pathway. The findings for men replicated these observations for polypharmacy, morbidity burden and patient complexity via indirect pathways. However, direct pathways showed unexpected associations between higher levels of multimorbidity and better safety. The consistent association between multimorbidity constructs and worse patient safety among women makes it advisable to target this group for the development of interventions, with particular attention to the role of comorbidity discordance. Further research, particularly qualitative research, is needed for clarifying the complex associations among men. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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14 pages, 840 KiB

Open AccessArticle

by Amelia Troncoso-Mariño, Albert Roso-Llorach, Tomás López-Jiménez, Noemí Villen, Ester Amado-Guirado, Sergio Fernández-Bertolin, Lucía A. Carrasco-Ribelles, Josep Ma Borras and Concepción Violán

J. Clin. Med. 2021, 10(4), 709; https://doi.org/10.3390/jcm10040709 - 11 Feb 2021

Cited by 14 | Viewed by 3200

Abstract

Aging, multimorbidity, and polypharmacy are associated with medication-related problems (MRPs). This study aimed to assess the association that multimorbidity and mortality have with MRPs in older people over time. We followed multimorbid, older (65–99 years) people in Catalonia from 2012 to 2016, using longitudinal data and Cox models to estimate adjusted hazard ratios (HR). We reviewed electronic health records to collect explanatory variables and MRPs (duplicate therapy, drug–drug interactions, potentially inappropriate medications (PIM), and contraindicated drugs in chronic kidney disease (CKD) or liver disease). There were 723,016 people (median age: 74 years; 58.9% women) who completed follow-up. We observed a significant (p < 0.001) increase in the proportion with at least one MRP (2012: 66.9% to 2016: 75.5%); contraindicated drugs in CKD (11.1 to 18.5%) and liver disease (3.9 to 5.3%); and PIMs (62.5 to 71.1%), especially drugs increasing fall risk (67.5%). People with ≥10 diseases had more MRPs (in 2016: PIMs, 89.6%; contraindicated drugs in CKD, 34.4%; and in liver disease, 9.3%). All MRPs were independently associated with mortality, from duplicate therapy (HR 1.06; 95% confidence interval (CI) 1.04–1.08) to interactions (HR 1.60; 95% CI 1.54–1.66). Ensuring safe pharmacological treatment in elderly, multimorbid patient remains a challenge for healthcare systems. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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14 pages, 636 KiB

Open AccessArticle

The Effect of a Comprehensive, Interdisciplinary Medication Review on Quality of Life and Medication Use in Community Dwelling Older People with Polypharmacy

by Donna Bosch-Lenders, Jesse Jansen, Henri E. J. H. (Jelle) Stoffers, Bjorn Winkens, Karin Aretz, Mascha Twellaar, Jos M. G. A. Schols, Paul-Hugo M. van der Kuy, J. André Knottnerus and Marjan van den Akker

J. Clin. Med. 2021, 10(4), 600; https://doi.org/10.3390/jcm10040600 - 5 Feb 2021

Cited by 10 | Viewed by 3516

Abstract

Background: We conducted a comprehensive medication review at the patients’ home, using data from electronic patient records, and with input from relevant specialists, general practitioners and pharmacists formulated and implemented recommendations to optimize medication use in patients aged 60+ years with polypharmacy. We evaluated the effect of this medication review on quality of life (QoL) and medication use. Methods: Cluster randomized controlled trial (stepped wedge), randomly assigning general practices to one of three consecutive steps. Patients received usual care until the intervention was implemented. Primary outcome was QoL (SF-36 and EQ-5D); secondary outcomes were medication changes, medication adherence and (instrumental) activities of daily living (ADL, iADL) which were measured at baseline, and around 6- and 12-months post intervention. Results: Twenty-four general practices included 360 women and 410 men with an average age of 75 years (SD 7.5). A positive effect on SF-36 mental health (estimated mean was stable in the intervention, but decreased in the control condition with −6.1, p = 0.009,) was found with a reduced number of medications at follow-up compared to the control condition. No significant effects were found on other QoL subscales, ADL, iADL or medication adherence. Conclusion: The medication review prevented decrease of mental health (SF36), with no significant effects on other outcome measures, apart from a reduction in the number of prescribed medications. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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11 pages, 607 KiB

Open AccessArticle

Multimorbidity Patterns and Unplanned Hospitalisation in a Cohort of Older Adults

by Roselyne Akugizibwe, Amaia Calderón-Larrañaga, Albert Roso-Llorach, Graziano Onder, Alessandra Marengoni, Alberto Zucchelli, Debora Rizzuto and Davide L. Vetrano

J. Clin. Med. 2020, 9(12), 4001; https://doi.org/10.3390/jcm9124001 - 10 Dec 2020

Cited by 32 | Viewed by 4420

Abstract

The presence of multiple chronic conditions (i.e., multimorbidity) increases the risk of hospitalisation in older adults. We aimed to examine the association between different multimorbidity patterns and unplanned hospitalisations over 5 years. To that end, 2,250 community-dwelling individuals aged 60 years and older from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were studied. Participants were grouped into six multimorbidity patterns using a fuzzy c-means cluster analysis. The associations between patterns and outcomes were tested using Cox models and negative binomial models. After 5 years, 937 (41.6%) participants experienced at least one unplanned hospitalisation. Compared to participants in the unspecific multimorbidity pattern, those in the cardiovascular diseases, anaemia and dementia pattern, the psychiatric disorders pattern and the metabolic and sleep disorders pattern presented with a higher hazard of first unplanned hospitalisation (hazard ratio range: 1.49–2.05; p < 0.05 for all), number of unplanned hospitalisations (incidence rate ratio (IRR) range: 1.89–2.44; p < 0.05 for all), in-hospital days (IRR range: 1.91–3.61; p < 0.05 for all), and 30-day unplanned readmissions (IRR range: 2.94–3.65; p < 0.05 for all). Different multimorbidity patterns displayed a differential association with unplanned hospital care utilisation. These findings call for a careful primary care follow-up of older adults with complex multimorbidity patterns. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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13 pages, 1924 KiB

Open AccessArticle

Socioeconomic Position, Multimorbidity and Mortality in a Population Cohort: The HUNT Study

by Kristin Hestmann Vinjerui, Johan H. Bjorngaard, Steinar Krokstad, Kirsty A. Douglas and Erik R. Sund

J. Clin. Med. 2020, 9(9), 2759; https://doi.org/10.3390/jcm9092759 - 26 Aug 2020

Cited by 12 | Viewed by 3022

Abstract

Multimorbidity and socioeconomic position are independently associated with mortality. We investigated the association of occupational position and several multimorbidity measures with all-cause mortality. A cohort of people aged 35 to 75 years who participated in the Trøndelag Health Study in 2006–2008 and had occupational data was linked to the Norwegian National Population Registry for all-cause mortality from study entry until 1 February 2019. Logistic regression models for each occupational group were used to analyze associations between the number of conditions and 10-year risk of death. Cox regression models were used to examine associations between combinations of multimorbidity, occupational position, and mortality. Analyses were conducted for men and women. Included were 31,132 adults (16,950 women (54.4%)); occupational groups: high, 7501 (24.1%); low, 15,261 (49.0%)). Increased mortality was associated with lower occupational group, more chronic conditions, and all multimorbidity measures. The joint impact of occupational group and multimorbidity on mortality was greater in men than women. All multimorbidity measures are strongly associated with mortality, with varying occupational gradients. Social differences in multimorbidity are a public health challenge and necessitate consideration in health care. Men in lower occupational groups seem to be a particularly vulnerable group. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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Review

Jump to: Editorial, Research

10 pages, 536 KiB

Open AccessReview

Innovative Strategies to Facilitate Patient-Centered Research in Multiple Chronic Conditions

by Tullika Garg, Courtney A. Polenick, Nancy Schoenborn, Jane Jih, Alexandra Hajduk, Melissa Y. Wei and Jaime Hughes

J. Clin. Med. 2021, 10(10), 2112; https://doi.org/10.3390/jcm10102112 - 14 May 2021

Cited by 6 | Viewed by 2967

Abstract

Multiple chronic conditions (MCC) are one of today’s most pressing healthcare concerns, affecting 25% of all Americans and 75% of older Americans. Clinical care for individuals with MCC is often complex, condition-centric, and poorly coordinated across multiple specialties and healthcare services. There is an urgent need for innovative patient-centered research and intervention development to address the unique needs of the growing population of individuals with MCC. In this commentary, we describe innovative methods and strategies to conduct patient-centered MCC research guided by the goals and objectives in the Department of Health and Human Services MCC Strategic Framework. We describe methods to (1) increase the external validity of trials for individuals with MCC; (2) study MCC epidemiology; (3) engage clinicians, communities, and patients into MCC research; and (4) address health equity to eliminate disparities. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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23 pages, 1239 KiB

Open AccessReview

AI and Big Data in Healthcare: Towards a More Comprehensive Research Framework for Multimorbidity

by Ljiljana Trtica Majnarić, František Babič, Shane O’Sullivan and Andreas Holzinger

J. Clin. Med. 2021, 10(4), 766; https://doi.org/10.3390/jcm10040766 - 14 Feb 2021

Cited by 51 | Viewed by 8636

Abstract

Multimorbidity refers to the coexistence of two or more chronic diseases in one person. Therefore, patients with multimorbidity have multiple and special care needs. However, in practice it is difficult to meet these needs because the organizational processes of current healthcare systems tend to be tailored to a single disease. To improve clinical decision making and patient care in multimorbidity, a radical change in the problem-solving approach to medical research and treatment is needed. In addition to the traditional reductionist approach, we propose interactive research supported by artificial intelligence (AI) and advanced big data analytics. Such research approach, when applied to data routinely collected in healthcare settings, provides an integrated platform for research tasks related to multimorbidity. This may include, for example, prediction, correlation, and classification problems based on multiple interaction factors. However, to realize the idea of this paradigm shift in multimorbidity research, the optimization, standardization, and most importantly, the integration of electronic health data into a common national and international research infrastructure is needed. Ultimately, there is a need for the integration and implementation of efficient AI approaches, particularly deep learning, into clinical routine directly within the workflows of the medical professionals. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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24 pages, 13983 KiB

Open AccessReview

End-of-Life Care Preferences of Older Patients with Multimorbidity: A Mixed Methods Systematic Review

by Ana I. González-González, Christine Schmucker, Julia Nothacker, Edris Nury, Truc Sophia Dinh, Maria-Sophie Brueckle, Jeanet W. Blom, Marjan van den Akker, Kristian Röttger, Odette Wegwarth, Tammy Hoffmann, Ferdinand M. Gerlach, Sharon E. Straus, Joerg J. Meerpohl and Christiane Muth

J. Clin. Med. 2021, 10(1), 91; https://doi.org/10.3390/jcm10010091 - 29 Dec 2020

Cited by 23 | Viewed by 4004

Abstract

Unpredictable disease trajectories make early clarification of end-of-life (EoL) care preferences in older patients with multimorbidity advisable. This mixed methods systematic review synthesizes studies and assesses such preferences. Two independent reviewers screened title/abstracts/full texts in seven databases, extracted data and used the Mixed Methods Appraisal Tool to assess risk of bias (RoB). We synthesized findings from 22 studies (3243 patients) narratively and, where possible, quantitatively. Nineteen studies assessed willingness to receive life-sustaining treatments (LSTs), six, the preferred place of care, and eight, preferences regarding shared decision-making processes. When unspecified, 21% of patients in four studies preferred any LST option. In three studies, fewer patients chose LST when faced with death and deteriorating health, and more when treatment promised life extension. In 13 studies, 67% and 48% of patients respectively were willing to receive cardiopulmonary resuscitation and mechanical ventilation, but willingness decreased with deteriorating health. Further, 52% of patients from three studies wished to die at home. Seven studies showed that unless incapacitated, most patients prefer to decide on their EoL care themselves. High non-response rates meant RoB was high in most studies. Knowledge of EoL care preferences of older patients with multimorbidity increases the chance such care will be provided. Full article

(This article belongs to the Special Issue Multimorbidity Development and Evolution: Clinical Implications)

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