A Framework for Crafting Clinical Practice Guidelines that are Relevant to the Care and Management of People with Multimorbidity

Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement.     

Precision Medicine,Healthy Living and the Complex Patient: Managing the Patient With Multimorbidity

Multimorbidity is the most common chronic health condition in adults and is associated with poor health outcomes. Optimal care for people with multimorbidity requires a person-centred approach that considers goals and preferences, improves quality of life and coordinates care across services. Because care is focused on patient outcomes, rather than disease outcomes, this provides an ideal setting for delivery of the Healthy Living Polypill (HLPP). Precision in delivery of the HLPP for people with multimorbidity involves active participation of patients in goal setting, strategies to address functional limitations and frailty, and support to develop the self-management skills necessary to adopt and sustain healthy behaviours. The multidisciplinary team is a key feature of integrated care for people with multimorbidity and all members should have the necessary skills to deliver the HLPP. Integration and continuity across health and social care sectors enhances outcomes and increases opportunities for personalised delivery of the HLPP.     

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease‐oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow‐up: strategies in care planning, self‐management and medication‐related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self‐management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.     

Quality of care assessment for people with multimorbidity

Multimorbidity, the simultaneous presence of multiple health conditions in an individual, is an increasingly common phenomenon globally. The systematic assessment of the quality of care delivered to people with multimorbidity will be key to informing the organization of services for meeting their complex needs. Yet, current assessments tend to focus on single conditions and do not capture the complex processes that are required for providing care for people with multimorbidity. We conducted a scoping review on quality of care and multimorbidity in selected databases in June 2018 and identified 87 documents as eligible for review, predominantly original research and reviews from North America, Europe and Australasia and mostly frequently related to primary care settings. We synthesized data qualitatively in terms of perceived challenges, evidence and proposed metrics. Findings reveal that the association between quality of care and multimorbidity is complex and depends on the conditions involved (quality appears to be higher for those with concordant conditions, and lower in the presence of discordant conditions) and the approach used for measuring quality (quality appears to be higher in people with multimorbidity when measured using condition/drug‐specific process or intermediate outcome indicators, and worse when using patient‐centred reports of experiences of care). People with discordant multimorbidity may be disadvantaged by current approaches to quality assessment, particularly when they are linked to financial incentives. A better understanding of models of care that best meet the needs of this group is needed for developing appropriate quality assessment frameworks. Capturing patient preferences and values and incorporate patients’ voices in the form of patient‐reported experiences and outcomes of care will be critical towards the achievement of high‐performing health systems that are responsive to the needs of people with multimorbidity.     

Addressing Multimorbidity in Evidence Integration and Synthesis

To minimize bias, clinical practice guidelines (CPG) for managing patients with multiple conditions should be informed by well-planned syntheses of the totality of the relevant evidence by means of systematic reviews and meta-analyses. However, deficiencies along the entire evidentiary pathway hinder the development of evidence-based CPGs. Published reports of trials and observational studies often do not provide usable data on treatment effect heterogeneity, perhaps because their design, analysis and presentation is seldom geared towards informing on how multimorbidity modifies the effect of treatments. Systematic reviews and meta-analyses inherit all the limitations of their building blocks and introduce additional of their own, including selection biases at the level of the included studies, ecological biases, and analytical challenges. To generate recommendations to help negotiate some of the challenges in synthesizing the primary literature, so that the results of the evidence synthesis is applicable to the care of those with multiple conditions. Informal group process. We have built upon established general guidance, and provide additional recommendations specific to systematic reviews that could improve the CPGs for multimorbid patients. We suggest that following the additional recommendations is good practice, but acknowledge that not all proposed recommendations are of equal importance, validity and feasibility, and that further work is needed to test and refine the recommendations.     

Prevalence,correlates and outcomes of multimorbidity among the middle-aged and elderly: Findings from the China Health and Retirement Longitudinal Study

BackgroundThe multimorbidity associated with ageing has been prevalent worldwide and poses major challenges to the health care system. However, the research about multimorbidity in China is far from sufficient. Additionally, international studies on the influencing factors of multimorbidity and the impact on disability/mortality are still inconsistent. The aim of this study was to examine the prevalence, correlates and outcomes of multimorbidity among the middle-aged and elderly Chinese population.MethodsWe used data from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression was performed to analyze the influencing factors of multimorbidity. The Cox proportional hazard model was used to evaluate the impact of multimorbidity on functional disability and all-cause mortality.ResultsThe prevalence of multimorbidity was 55.12 % in the whole study population and 65.60 % among people aged ≥ 65 years. Multimorbidity was significantly associated with old age (OR: 2.76, 95 % CI: 2.31–3.30), females (OR: 1.21, 95 % CI: 1.01–1.44), ex-smoker (OR: 2.07, 95 % CI: 1.58–2.72), ex-drinker (OR: 2.18, 95 % CI: 1.66–2.87), obesity (OR: 2.87, 95 % CI: 2.30–3.57), lower education (OR:1.32, 95 % CI: 1.08–1.61), living alone (OR: 1.26, 95 % CI: 1.02–1.55) and unemployment (OR: 1.66, 95 % CI: 1.11–2.48). Moreover, multimorbidity was correlated with disability (HR: 2.27, 95 % CI: 1.93–2.66) and all-cause mortality (HR: 1.95, 95 % CI: 1.36–2.80) after multivariable adjustment.ConclusionsMultimorbidity is highly prevalent in China and possesses significantly negative effects on health outcomes. Identification of the key population and tailored interventions on their modifiable risk factors should be paid much importance.     

Percutaneous closure of the patent ductus arteriosus: opportunities moving forward

The optimal treatment method for infants with a patent ductus arteriosus (PDA) necessitating closure remains a subject of controversy and debate. While the risks associated with surgical PDA ligation are well described, the available evidence base for alternative management strategies during infancy, including percutaneous closure or conservative (nonintervention) management, are not well explored. Among infants, the goals of this review are to: (a) use rigorous systematic review methodology to assess the quality and quantity of published reports on percutaneous closure vs surgical ligation; (b) compare outcomes of percutaneous closure vs conservative management; and (c) based on recommendations from the International PDA symposium, to elucidate needs and opportunities for future research and interdisciplinary collaboration. The available evidence base, as well as on broad consensus reached at the International PDA Symposium, suggests that a contemporary, pragmatic clinical trial comparing PDA treatment strategies is warranted. Additionally, quality assurance safeguards are necessary in the implementation of newer PDA closure devices. Finally, to determine best approaches to treatment for infants with PDA, tools for consistent data collection and reporting across centers and disciplines are needed to minimize heterogeneity and permit pooled analysis.     

Guide to designing, conducting, publishing and communicating results of clinical studies involving probiotic applications in human participants

The heterogeneity of human clinical trials to assess the effectiveness of probiotics presents challenges regarding interpretation and comparison. Evidence obtained from clinical trials among a population with a disease or specific risk factors may not be generalizable to healthy individuals. The evaluation of interventions in healthy persons requires careful selection of outcomes due to the absence of health indicators and the low incidence of preventable conditions. Given the tremendous resources invested in such trials, development of consistent approaches to assessing the effectiveness of probiotics would be beneficial. Furthermore, the reporting, presentation and communication of results may also affect the validity of the scientific evidence obtained from a trial. This review outlines the challenges associated with the design, implementation, data analysis and interpretation of clinical trials in humans involving probiotics. Best practices related to their design are offered along with recommendations for enhanced collaboration to advance research in this emerging field.     

Health and social needs of older Australians from culturally and linguistically diverse backgrounds: issues and implications

Australia has one of the most diverse migrant populations in the world. This pattern of cultural diversity is also reflected in the older population, with increasing numbers of older people from culturally and linguistically diverse (CALD) backgrounds. The aim of the present review is to examine the evidence base related to the health and social needs and existing support systems for older Australians from CALD backgrounds. It is difficult to generalise the issues and challenges associated with these groups because of their heterogeneity, both between and within groups. However, their health and social needs may be particularly acute as a result of cultural and language barriers; their geographical location and the circumstances of migration, which impact on their financial circumstances as well as psycho‐social health. Whilst there is a range of community and government stakeholders involved in addressing these issues, the evidence base for policy and practice is not well understood.     

Patterns and impact of comorbidity and multimorbidity among community-resident American Indian elders

PURPOSE: The purpose of this study is to suggest a new approach to identifying patterns of comorbidity and multimorbidity. DESIGN AND METHODS: A random sample of 1,039 rural community-resident American Indian elders aged 60 years and older was surveyed. Comorbidity was investigated with four standard approaches, and with cluster analysis. RESULTS: Most respondents (57%) reported 3 or more of 11 chronic conditions. Cluster analysis revealed a four-cluster comorbidity structure: cardiopulmonary, sensory-motor, depression, and arthritis. When the impact of comorbidity on four health-related quality of life outcomes was tested, the use of the clusters offered more explanatory power than the other approaches. IMPLICATIONS: Our study improves understanding of comorbidity within an understudied and underserved population by characterizing comorbidity in conventional and novel ways. The cluster approach has four advantages over previous approaches. In particular, cluster analysis identifies specific health problems that have to be addressed to alter American Indian elders' health-related quality of life.     

Predictors of social leisure activities in older Europeans with and without multimorbidity

Older people spend much time participating in leisure activities, such as taking part in organized activities and going out, but the extent of participation may differ according to both individual and environmental resources available. Chronic health problems become more prevalent at higher ages and likely necessitate tapping different resources to maintain social participation. This paper compares predictors of participation in social leisure activities between older people with and those without multimorbidity. The European Project on Osteoarthritis (EPOSA) was conducted in Germany, UK, Italy, The Netherlands, Spain and Sweden (N = 2942, mean age 74.2 (5.2)). Multivariate regression was used to predict social leisure participation and degree of participation in people with and without multimorbidity. Fewer older people with multimorbidity participated in social leisure activities (90.6 %), compared to those without multimorbidity (93.9 %). The frequency of participation was also lower compared to people without multimorbidity. Higher socioeconomic status, widowhood, a larger network of friends, volunteering, transportation possibilities and having fewer depressive symptoms were important for (the degree of) social leisure participation. Statistically significant differences between the multimorbidity groups were observed for volunteering and driving a car, which were more important predictors of participation in those with multimorbidity. In contrast, self-reported income appeared more important for those without multimorbidity, compared to those who had multimorbidity. Policies focusing on social (network of friends), physical (physical performance) and psychological factors (depressive symptoms) and on transportation possibilities are recommended to enable all older people to participate in social leisure activities.     

Multimorbidity and mortality in older adults: A systematic review and meta-analysis

ObjectiveTo review literature and provide a pooled effect for the association between multimorbidity and mortality in older adults.MethodsA systematic review was performed of articles held on the PUBMED database published up until January 2015. Studies which used different diseases and other conditions to define frailty, evaluated multimorbidity related only to mental health or which presented disease homogeneity were not included. A meta-analysis using random effect to obtain a pooled effect of multimorbidity on mortality in older adults was conducted only with studies which reported hazard ratio (HR). Stratified analysis and univariate meta-regression were performed to evaluate sources of heterogeneity.ResultsOut of 5806 identified articles, 26 were included in meta-analysis. Overall, positive association between multimorbidity and mortality [HR: 1.44 (95%CI: 1.34; 1.55)] was detected. The number of morbidities was positively related to risk of death [HR: 1.20 (95%CI: 1.10; 1.30)]. Compared to individuals without multimorbidity, the risk of death was 1.73 (95%CI: 1.41; 2.13) and 2.72 (95%CI: 1.81; 4.08) for people with 2 or more and 3 or more morbidities, respectively. Heterogeneity between studies was high (96.5%). The sample, adjustment and follow-up modified the associations. Only nine estimates performed adjustment which included demographic, socioeconomic and behaviour variables. Disabilities appear to mediate the effect of multimorbidity on mortality.ConclusionsMultimorbidity was associated with an increase in risk of death. Multimorbidity measurement standardization is needed to produce more comparable estimates. Adjusted analysis which includes potential confounders might contribute to better understanding of causal relationships between multimorbidity and mortality.     

Fit for caring: factors associated with informal care provision by older caregivers with and without multimorbidity

Due to an increased prevalence of chronic diseases, older individuals may experience a deterioration of their health condition in older ages, limiting their capacity for social engagement and in turn their well-being in later life. Focusing on care provision to grandchildren and (older) relatives (‘informal care’) as forms of engagement, this paper aims to identify which individual characteristics may compensate for health deficits and enable individuals with multimorbidity to provide informal care. We use data from the SHARE survey (2004–2012) for individuals aged 60 years and above in 10 European countries. Logistic regression estimates for the impact of different sets of characteristics on the decision to provide care are presented separately for people with and without multimorbidity. Adapting Arber and Ginn’s resource theory, we expected that older caregivers’ resources (e.g., income or having a spouse) would facilitate informal care provision to a greater extent for people with multimorbidity compared to those without multimorbidity, but this result was not confirmed. While care provision rates are lower among individuals suffering from chronic conditions, the factors associated with caregiving for the most part do not differ significantly between the two groups. Results, however, hint at reciprocal intergenerational support patterns within families, as the very old with multimorbidity are more likely to provide care than those without multimorbidity. Also, traditional gender roles for women are likely to be weakened in the presence of health problems, as highlighted by a lack of gender differences in care provision among people with multimorbidity.     

Quality of Care for Patients with Multiple Chronic Conditions: The Role of Comorbidity Interrelatedness

Multimorbidity—the presence of multiple chronic conditions in a patient—has a profound impact on health, health care utilization, and associated costs. Definitions of multimorbidity in clinical care and research have evolved over time, initially focusing on a patient’s number of comorbidities and the associated magnitude of required care processes, and later recognizing the potential influence of comorbidity characteristics on patient care and outcomes. In this article, we review the relationship between multimorbidity and quality of care, and discuss how this relationship may be mediated by the degree to which conditions interact with one another to generate clinical complexity (comorbidity interrelatedness). Drawing on established theoretical frameworks from cognitive engineering and biomedical informatics, we describe how interactions among conditions result in clinical complexity and may affect quality of care. We discuss how this comorbidity interrelatedness influences the value of existing quality guidelines and performance metrics, and describe opportunities to quantify this construct using data widely available through electronic health records. Incorporating comorbidity interrelatedness into conceptualizations of multimorbidity has the potential to enhance clinical and research efforts that aim to improve care for patients with multiple chronic conditions.     

Patterns of Chronic Multimorbidity in the Elderly Population

OBJECTIVES: To describe patterns of comorbidity and multimorbidity in elderly people.
DESIGN: A community-based survey.
SETTING: Data were gathered from the Kungsholmen Project, a urban, community-based prospective cohort in Sweden.
PARTICIPANTS: Adults aged 77 and older living in the community and in institutions of the geographically defined Kungsholmen area of Stockholm (N=1,099).
MEASUREMENTS: Diagnoses based on physicians' examinations and supported by hospital records, drug use, and blood samples. Patterns of comorbidity and multimorbidity were evaluated using four analytical approaches: prevalence figures, conditional count, logistic regression models, and cluster analysis.
RESULTS: Visual impairments and heart failure were the diseases with the highest comorbidity (mean 2.9 and 2.6 co-occurring conditions, respectively), whereas dementia had the lowest (mean 1.4 comorbidities). Heart failure occurred rarely without any comorbidity (0.4%). The observed prevalence of comorbid pairs of conditions exceeded the expected prevalence for several circulatory diseases and for dementia and depression. Logistic regression analyses detected similar comorbid pairs. The cluster analysis revealed five clusters. Two clusters included vascular conditions (circulatory and cardiopulmonary clusters), and another included mental diseases along with musculoskeletal disorders. The last two clusters included only one major disease each (diabetes mellitus and malignancy) together with their most common consequences (visual impairment and anemia, respectively).
CONCLUSION: In persons with multimorbidity, there exists co-occurrence of diseases beyond chance, which clinicians need to take into account in their daily practice. Some pathological mechanisms behind the identified clusters are well known; others need further clarification to identify possible preventative strategies.     

Factors associated with immune checkpoint inhibitor use among older adults with late-stage melanoma: A population-based study

Improvement in overall survival by immune checkpoint inhibitors (ICI) treatment in clinical trials encourages their use for late-stage melanoma. However, in the real-world, heterogeneity of population, such as older patients with multimorbidity, may lead to a slower diffusion of ICIs. The objective of this study was to examine the association of multimorbidity and other factors to ICI use among older patients with late-stage melanoma using real world data.A retrospective cohort study design with a 12-month baseline and follow-up period was adopted with data from the linked Surveillance, Epidemiology, and End Results cancer registry/Medicare database. Older patients (>65 years) with late-stage (stage III/IV) melanoma diagnosed between 2012 and 2015 were categorized as with or without multimorbidity (presence of 2 or more chronic conditions) and ICI use was identified in the post-index period. Chi-square tests and logistic regression were used to evaluate factors associated with ICI use.In the study cohort, 85% had multimorbidity, 18% received any treatment (chemotherapy, radiation, and/or ICI), and 6% received ICI. Only 5.5% of older patients with multimorbidity and 6% without multimorbidity received ICIs. Younger age, presence of social support, lower economic status, residence in northeastern regions, and recent year of diagnosis were significantly associated with ICI use; however, multimorbidity, sex, and race were not associated with ICI use.In the real-world clinical practice, only 1 in 18 older adults with late stage melanoma received ICI, suggesting slow pace of diffusion of innovation. However, multimorbidity was not a barrier to ICI use.     

Aging and infectious diseases: do patterns of comorbidity vary by HIV status, age, and HIV severity?

Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%-63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count <200 cells/mm(3); hypertension was associated with CD4 cell count >200 cells/mm(3). Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection.     

Effektgrößen in klinischen Studien bei Patienten mit Rheumatoider Arthritis EULAR Guidelines und OMERACT Core-sets

Clinical trials in rheumatology are confronted with new challenges. The pharmaceutical industry must be more efficient in identifying and marketing new drugs, regulatory authorities require additional evidence about the effectiveness of new compounds, and the consumer including physicians require more transparency in the selection and use of appropriate outcomes in clinical trials. These challenges find their common denominator in a further standardization of clinical trials that extends beyond the application of Good Clinical Practice. For years, national and international organizations have developed recommendations for the selection of appropriate outcomes in RA clinical trials. However, these recommendations have rarely been data driven or evidence based. The international informal collaboration Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) has contributed enormously towards the application of a standardized methodology in the development of recommendations to enhance the quality of research in clinical rheumatology. The scope of this initiative goes now far beyond rheumatoid arthritis and now covers all major rheumatic conditions.     

Thromboembolieprophylaxe in der Inneren Medizin und der hausärztlichen Versorgung

Although up to 80% of fatal pulmonary emboli occur in nonsurgical patients, conclusive studies on the prevention of thrombosis have only become available in the last 10 years. Bedridden inpatients with acute medical diseases require pharmacologic prophylaxis for thrombosis with unfractionated or low molecular weight heparin or with fondaparinux. This also holds true for patients with underlying malignancies or those suffering from acute ischemic stroke or paretic leg. The challenges to thrombosis prophylaxis are posed by ensuring that uninterrupted prophylaxis is continued after hospital discharge in cases of persisting risk, determining the indications and applying thrombosis prophylaxis on an outpatient basis as well as the multimorbidity and often advanced age of the internal medicine patients. The last factor not only entails an elevated risk of thromboembolism but also an increased risk of hemorrhage, especially in patients with renal insufficiency or platelet inhibitors. Product-specific recommendations and restrictions on pharmacologic prophylaxis need to be considered. Thromboprophylaxis as applied in internal medicine and family practice represents an effective measure to prevent symptomatic and fatal thromboembolisms, but due to multimorbidity and polytherapy of medical patients it requires careful monitoring.