Entete 3

Comorbidity and progression of late onset Alzheimer’s Disease: A systematic review

By Miriam L. Haaksma
and Lara R. Vilela, Alessandra Marengoni, Amaia Calderón-Larrañaga, Jeannie-Marie S. Leoutsakos, Marcel G.M. Olde Rikkert, René J.F. Melis.
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Alzheimer’s disease is a neurodegenerative syndrome characterized by multiple dimensions including cognitive decline, decreased daily functioning and psychiatric symptoms. This systematic review [1] aimed to investigate the relation between somatic comorbidity burden and progression in late-onset Alzheimer’s disease (LOAD). We searched four databases for observational studies that examined cross-sectional or longitudinal associations of cognitive or functional or neuropsychiatric outcomes with comorbidity in individuals with LOAD. From the 7966 articles identified originally, 11 studies were included in this review. Nine studies indicated that comorbidity burden was associated with deterioration in at least one of the three dimensions of LOAD examined. Seven out of ten studies investigating cognition found comorbidities to be related to decreased cognitive performance. Five out of the seven studies investigating daily functioning showed an association between comorbidity burden and decreased daily functioning. Neuropsychiatric symptoms (NPS) increased with increasing comorbidity burden in two out of three studies investigating NPS. Associations were predominantly found in studies analyzing the association cross-sectionally, in a time-varying manner or across short follow-up (≤2 years). Rarely baseline comorbidity burden appeared to be associated with outcomes in studies analyzing progression over longer follow-up periods (>2 years). This review provides evidence of an association between somatic comorbidities and multifaceted LOAD progression. Given that time-varying comorbidity burden, but much less so baseline comorbidity burden, was associated with the three dimensions prospectively, this relationship cannot be reduced to a simple cause-effect relation and is more likely to be dynamic. Therefore, both future studies and clinical practice may benefit from regarding comorbidity as a modifiable factor with a possibly fluctuating influence on LOAD.
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Is it possible to improve drug prescription in primary care patients with multimorbidity and polypharmacy by implementing the Ariadne principles in clinical practice?

By Alexandra Prados Torres
This is the question that Multi-PAP is trying to answer.
Multi-PAP is a coordinated multicentre project aimed at designing and measuring the effectiveness of a complex intervention in primary care for improving drug prescription in multimorbid patients compared to usual care. The intervention is based on the Ariadne principles designed by Muth et al. in 2014, and consists of two components: training of General Practitioners (GP) and GP-patient interviews.
Training of physicians has been conceived as a 4-weeks massive online open course (MOOC) designed by a multidisciplinary team with emphasis in multimorbidity, polypharmacy, medication appropriateness and adherence, and the Ariadne principles and tools for their implementation in clinical practice. During GP-patient interviews that will be conducted over a month, physicians are expected to put into practice the knowledge acquired during the training.
To measure the effectiveness of this intervention, Multi-PAP is conducting a pragmatic cluster randomized clinical trial (RCT) in primary care health centres in three regions in Spain (Aragon, Madrid and Andalusia). The unit of randomization is the family physician (N=80), and the unit of analysis is the patient. The study population is conformed by 400 patients (200 per study arm) aged 65–74 years with multimorbidity (defined as presence of 3 or more chronic diseases) and polypharmacy (defined as 5 or more drugs prescribed in ≥3 months). The intervention is based on the implementation of the Ariadne principles (GP training and GP-patient interviews) and it is compared to usual care. The main outcomes, to be measured at months 6 and 12, are: MAI score, health services use, quality of life, pharmacotherapy and adherence to treatment, and clinical and socio-demographic variables.
This project is justified by the need to provide evidence concerning interventions on primary care patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes.
This RCT is registered in Clinicaltrials.gov (NCT02866799). Accessible at:
The full-text protocol of Multi-PAP RCT is accessible at: http://rdcu.be/rErC

Book: Aging, Place, and Health: A Global Perspective

By: William A. Satariano, and Marlon Maus
This book represents a collaboration of experts in the field of aging and public health. The present book builds on the first edition of the book (Epidemiology of Aging:  An Ecological Approach. Satariano, 2006).
Various international researchers and practitioners were asked to join the project based on their expertise in particular areas of aging research, practice, and policy. This has resulted in a book that presents each topic, e.g., cognitive function, as an outcome in epidemiological research.  In addition, each chapter considers conceptual and measurement issues, implications for practice and policy, and future directions for research.  The book stresses a global perspective identifying work from countries throughout the world, not just the U.S.
This edition of the book is intended to target a wide audience which includes not only other experts in the field and academics, but also students, practitioners and interested researchers from other disciplines. The book is intended to help inspire further progress in the global effort towards what the World Health Organization has described as a “state of complete physical, mental, and social well-being, not merely the absence of disease or infirmity” of our older population.
Chapter 8, Disease, Comorbidity, and Multimorbidity, by Martin Fortin, Aline Ramond, Cynthia Boyd, and Jose Almirall focuses on multimorbidity (MM). The authors explore how the several coexisting health conditions in a single individual negatively affect an individuals’ health-related outcomes (functional status, social participation, quality of life, life expectancy) and is also responsible for numerous impacts on society (healthcare utilization, direct and indirect costs). The importance of MM is now acknowledged as a research priority in health care, and in-depth understanding of its main determinants is required as a first step in this direction. This chapter helps distinguish MM-related essential definitions and concepts and successively addresses the role of sociodemographics, socioeconomic factors, social networks, social capital, genetics, lifestyle, psychological and psychosocial factors, and polypharmacy as potential risk factors for MM, following an ecological model of health. Finally, the chapter highlights current gaps in the literature as well as specific challenges, and suggests future directions for MM epidemiology research.

Multimorbidity as a complex systems phenomenon: a series exploring this perspective from the Journal of Evaluation in Clinical Practice

By René Melis
Multimorbidity is one of public health and healthcare’s top priorities. Yet despite this, healthcare continues to struggle to provide solutions to deal with multimorbidity in healthcare that work. It is recognized that our healthcare systems – due to their focus on the acute phase of single diseases – are not well positioned to deal with multimorbidity. Unfortunately, our dealings with changing the system do not easily translate into successes: there are so many stakeholders involved and multimorbidity is interconnected with a huge number of aspects of life and society. Where to begin? Our multimorbidity challenge has all the characteristics of a “wicked problem”: a societal problem that is so complex that is seems difficult or even impossible to solve. In the most recent Complexity Forum of the Journal of Evaluation in Clinical Practice a series of articles explore multimorbidity and how we should shape our healthcare from the perspective of complex systems thinking (http://onlinelibrary.wiley.com/doi/10.1111/jep.12723/full). Rather than a stable, albeit complicated, arrangement of individual elements with predictable results following from inputs in a linear way, a complex system is a dynamic, ecological system in which outcomes seem to emerge quite unpredictably out of the interaction of the starting conditioning. For the reasons mentioned above, this “complexity” approach might fit very well to the multimorbidity challenge.
The series starts with an introductory paper of Dr Joachim Sturmberg and colleagues. Sturmberg, who is a general practitioner as well as a longstanding expert on complexity in health (care systems), together with his colleagues explore how taking multimorbidity as a complexity phenomenon might shape integrated, personalized care differently. Following, this work is commented on by several authors from different perspectives. Being a “wicked problem” neither of these works provide a miracle potion to solve our multimorbidity issue, however, the richness of the perspectives included does shed new light. The famous Cynefin framework (https://hbr.org/2007/11/a-leaders-framework-for-decision-making) for management problems tells us that managing complex problems – and multimorbidity sure is! – has to begin with uncovering the “unknown unknowns” and we need to “probe first, then sense, and then respond”. The latter is what this series hopefully has to offer to the multimorbidity community.

Brazilian Group of Studies about Multimorbidity

By Bruno P Nunes and Sandro R Rodrigues Batista
We are very satisfied to inform the International Research Community on Multimorbidity (an important encouraging community of our work) about the creation of the Brazilian Group of Studies about Multimorbidity (named in Portuguese: Grupo Brasileiro de Estudos sobre Multimorbidade – GBEM). The group is headed by Bruno P Nunes and Sandro R Rodrigues Batista, two researchers from Brazil. The group is already formalized in the Brazilian national research platform of the Brazilian National Council for Scientific and Technological Development
Furthermore, we are described in ResearchGate too
Currently, we have more than 20 Brazilian researchers and some international collaborators, including researchers from Chile, Colombia, EUA, India, Peru, Portugal and Sri Lanka. One of our research goals as a group is to improve epidemiological information about multimorbidity in Low and Middle Income Countries, mainly in Brazil and South America. We are using a platform for planning our work and intend to publish the first scientific results of the partnership by the end of 2017. The articles already published by group members can be viewed in the ResearchGate website. Furthermore, we are looking for researchers interested in cross-country comparisons about a wide range of issues related to multimorbidity (prevalence, patterns, inequalities, use of health services and others) to be included in the GBEM. Contact e-mail for further information: nunesbp@gmail.com/ sandrorbatista@gmail.com/ gbemulti@gmail.com.

Assessing and measuring chronic multimorbidity in the older population

By Amaia Calderón-Larrañaga and Davide L Vetrano
Multimorbidity is one of the main challenges facing health systems worldwide. While its definition as “the simultaneous presence of two or more chronic diseases” is well established, its operationalization is not yet agreed. This study aimed to provide a clinically-driven comprehensive list of chronic conditions to be included when measuring multimorbidity.
Based on a consensus definition of chronic disease, all codes from the International Classification of Diseases 10th revision (ICD-10) were classified as chronic or not by an international team of physicians and epidemiologists specialized in geriatrics and family medicine, and were subsequently grouped into broader categories. Last, we showed proof of concept by applying the classification to older adults from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K).
An initial number of 918 chronic ICD-10 codes were identified and grouped into 60 chronic disease categories. In SNAC-K, 88.6% had ≥2 of these 60 disease categories, 73.2% had ≥3, and 55.8% had ≥4. Once validated, this operational measure of multimorbidity may enable the advancement and evolution of conceptual and theoretical aspects of multimorbidity that will eventually lead to better care.
The publication can be found in the following link:

European guidelines on nutritional support for polymorbid (multimorbid) internal medicine patients

By Filomena Gomes and Philipp Schuetz
The European Society for Clinical Nutrition and Metabolism (ESPEN) holds several guidelines and position papers which guide clinicians in providing nutritional support in particular groups of patients, usually disease or age specific (http://www.espen.org/education/espen-guidelines).
However, many of the patients requiring nutritional support may suffer from multiple diseases. In fact, polymorbidity (multimorbidity) is highly prevalent, affecting more than 70% of the hospitalized adult population, and is associated with higher mortality and costs. In this context, a group of 14 European experts is developing guidelines on nutritional support for polymorbid (multimorbid) internal medicine patients, with the aim to help clinicians who struggle with the uncertainties of applying disease-specific guidelines to their patients who suffer from multiple conditions.
This project, which is endorsed by ESPEN, started with an initial meeting in Zurich, in January 2015, and the methodology used follows the standard operating procedures for ESPEN guidelines (Clinical Nutrition. 2015;34(6):1043-51). The working group has developed 12 important clinical questions, covering different areas of nutritional support: indication, route of feeding, energy, protein, micronutrients, disease-specific nutrients, timing, monitoring and procedure of intervention. Systematic literature searches were conducted in 3 different databases (as well as in secondary sources) resulting in a total of 4532 retrieved abstracts. These abstracts were screened to identify papers which meet the inclusion criteria; the quality of the included papers was evaluated and a level of evidence was assigned, which then resulted in a proposal of 22 recommendations and 4 statements. The first DELPHI online voting for these recommendations and statements is now completed and a final consensus conference will take place in April 2017, which will be followed by the preparation of the manuscript for publication.

Publications on multimorbidity October – December 2016

By Martin Fortin
Our search for papers on multimorbidity that were published during the period October – December 2016 has been completed. As in previous searches, we found many new papers and the list is too long for this venue. Therefore, we have prepared a PDF file that can be accessed following this link.
Probably, there are some publications that were not detected by our search strategy using the terms “multimorbidity”, “multi-morbidity” and the expression “multiple chronic diseases” in PubMed (https://www.ncbi.nlm.nih.gov/pubmed), but we are sure that most publications on the subject are included in the list.
All references are also included in our library. Feel free to share with anyone interested in multimorbidity.

Perceived stress and multimorbidity

By Anders Prior
Multimorbidity and especially mental-physical multimorbidity is an increasing concern worldwide. It is well-known that psychiatric illness impairs the prognosis in persons with chronic physical disease. However, little is known on the impact of non-syndromic mental stress; mental stress is common in the general population, and psychological problems are an increasingly frequent reason for primary care contacts. In two studies, we aimed to determine whether perceived mental stress is associated with potentially preventable hospitalizations and all-cause mortality in persons with various degrees of multimorbidity.
The Danish Civil Registration System allowed us to individually link health survey data with prospectively collected data from Danish health registers creating a unique population-based cohort.  The Danish National Health Survey 2010 provided data on e.g. perceived stress and lifestyle factors on a representative sample of 118,000 Danish citizens aged 25 or older. Danish health registers provided data on hospitalizations, demographic and socioeconomic factors. We developed a new Danish multimorbidity index based on recorded diagnoses and redeemed medicine prescriptions on all Danish citizens identifying 39 mental and physical long-term conditions. We adjusted for and analyzed the modifying effect of multimorbidity on the study outcomes.
In general, we found that high stress perception was associated with multimorbidity, an increased number of potentially preventable hospitalizations and increased all-cause mortality after adjusting for mental-physical multimorbidity, socioeconomic factors and lifestyle where appropriate, and there often seemed to be dose-response relations. In absolute numbers, persons with multimorbidity had a poorer prognosis and psychiatric conditions aggravated this.
This may be the first step to understand the impact of mental stress on physical health, to discuss mental stress in a general practice setting, and to create the foundation for developing potential interventions and practice guidelines for patients with stress in general practice. Hopefully, this may lead to better care and improved life expectancy of people with stress and chronic disease.
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References
Prior A, Fenger-Grøn M, Larsen KK, et al. The association between perceived stress and mortality among people with multimorbidity: A prospective population-based cohort study. Am J Epidemiol. 2016;184(3):199-210.
Prior A, Vestergaard M, Davydow DS, et al. Perceived stress, multimorbidity, and risk for hospitalizations for ambulatory care-sensitive conditions: A population-based cohort study. Med Care. 2017;55(2):131-139.

Different multimorbidity measures affect estimated levels of physical quality of life

By Aline Ramond-Roquin
Health-related quality of life is adversely affected by the presence of multimorbidity in a way that an increasing number of concurrent chronic conditions is associated with lower scores of health-related quality of life. Studies aiming to quantify the impact of multimorbidity on the quality of life show wide heterogeneity in terms of the intensity of this association but these studies also present other important methodological differences such as population studied, measure of quality of life, measure of multimorbidity, etc.
Most operational definitions of multimorbidity have been based on a simple count of conditions which are screened as present or not in a given individual from a predetermined list of conditions. Many different lists of potential conditions have been proposed, with some being as short as six conditions and others as long as 40.
We investigated the influence of the list of conditions on the estimated level of the physical component of health-related quality of life in individuals with multimorbidity and found that the length of the list of candidate conditions considered has a great impact on the estimations of physical health-related quality of life.
This argues for careful methodological consideration when measuring multimorbidity and its association with different outcomes. We conclude that standardization of the measure of multimorbidity is needed to allow the comparison of the results across different studies on multimorbidity.
The article describing this study was published on line (1) and is freely accessible to those interested in this subject.
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Reference
1) Ramond-Roquin A, Haggerty J, Lambert M, Almirall J, Fortin M: Different Multimorbidity Measures Result in Varying Estimated Levels of Physical Quality of Life in Individuals with Multimorbidity: A Cross-Sectional Study in the General Population. Biomed Res Int. 2016;2016:7845438.