Keywords

Introduction

The risk of falling ill rises with increasing age. Due to the aging of the population and to advances in medical care and public health that have allowed people to live longer with incurable diseases, the number and proportion of patients with chronic diseases are growing [1]. If two or more chronic diseases exist at the same time, the state of health of the patient can be referred to as multimorbid. On average, there are five diagnoses in 65–70-year-olds, seven diagnoses in 70–80-year-olds and over eight diagnoses in 80–84-year-olds [2]. Accurate data on the prevalence of multimorbidity are available of only a few studies in Europe. A study that was conducted in several Dutch general practice centers described a prevalence of 15 % for over 60 years old patients. According to the results of a database analysis of 42 general practice centers in Germany a prevalence of 78 % was present in patients aged 80 and over. The “Seven Countries Study” described a prevalence of 10–15 % in men aged 65–84 years with different accumulation depending on the region. In Germany, 40 % of patients over 65 years had up to four diseases at the same time and over 16 % more than four diseases [3]. Because certain conditions heighten the risk of developing other conditions, patients with multimorbidity are likely to accumulate more diagnoses and experience escalating clinical complexity [4, 5].

The prevalence of multimorbidity varies by age, country and investigated patient population. The high variability in prevalence has its basis in the different definitions of multimorbidity, which were used by the researchers. However, even if the values are far apart, they show the significance of multimorbidity for healthcare utilization and costs [6]. Approximately 80 % of spending in the national health insurance accounts for 20 % of the insured person with one or more chronic diseases [7]. In the recent analysis of the PRISCUS study, the average annual direct costs for elderly patients without multimorbidity were at 1250 € in Germany. In patients with two chronic conditions, the average annual direct costs were at € 1962 and in patients with more than ten chronic diseases even at € 6862. Therefore, the impact of multimorbidity on the social security systems are highly relevant because with an increasing number of diseases the cost of care increases predominantly linear (sometimes even exponentially) [8]. Multimorbidity is especially associated with high health care utilization and cost when it is accompanied by functional limitations. In the future, the health systems will thus face major challenges when decisions have to be made about the type of care, on the allocation of services as well as on the financing of the funding [9]. In a systematic review on the association between multimorbidity and health costs, Hodek et al. notes that the knowledge of the impact of chronic (multiple) diseases and possible combinations is of great significance to improve the care of people with multimorbidity, to use resources more efficiently and thus ultimately reduce costs [8].

Multimorbidity may also lead to polypharmacy, i.e. the administration of four or more simultaneously prescribed drugs, which in turn is a serious pharmacological problem [10]. Due to the large number of prescribed drugs the risk of adverse drug reactions increases and thus for the subsequent health care utilization in practices and clinics [11]. Multimorbidity also presents challenges in the development of guidelines and treatment recommendations, which are still largely unresolved. Clinical guidelines limit their recommendations yet often on single diseases. In clinical research, patients with multiple diseases are often excluded. Kaplan and Feinstein explained to the resulting bias: “In clinical practice, the prognostic influences of age and comorbidity are well recognized, and these influences usually receive careful consideration during the diverse decisions of clinical judgment. In statistical studies, the effects of comorbidity are generally ignored [12].”

According to de Groot et al., there are four important reasons to measure multimorbidity in studies [13]. The first reason is to be able to correct confounders, and thereby improve the internal validity of the study. A confounder is a factor that is not directly subject of the investigation. But both the intervention/exposure as well as the target size is associated with the confounder. Thus confounders could cause “confusion” in statements about the relationship between intervention/exposure and target [14]. The second reason is to be able to identify effect modification. Effect modification means the effect of a factor to a disease characterized by the presence of another factor, which means that there is an interaction between the two factors [15]. The third reason is the wish to use multimorbidity as a predictor of survival or progression of patients in studies [16]. The final reason is that a comprehensive measure for multimorbidity, which summarizes many coexisting diseases in a score, is useful for reasons of statistical efficiency.

In the literature there are a wide variety of methods to measure multimorbidity in patients. A common method is to determine the total number of diseases and the detection of chronic diseases among an underlying disease. For example, the Charlson Comorbidity Index captures both the number and severity of each disease. But a standarized procedure for the measurement of multimorbidity does not exist so far [17]. Therefore Professor Cornel Sieber, Chair of Geriatrics at the University of Erlangen-Nuremberg, criticized in a press release prior to the 118th German Internist Congress in Wiesbaden, that currently no consensus in the definition of multimorbidity and the number and type of considered diseases exists [3].

The closely interrelated concepts multimorbidity, comorbidity and frailty are defined in this capital, and then the current methods are compiled and evaluated as multimorbidity has so far been operationalized. Furthermore, the influence of the concepts will be explained on patient outcome.

Definitions

Multimorbidity

The term ‘multimorbidity’ first appeared in a German publication in 1976. For the next 14 years the term was restricted almost entirely to German publications. The term ‘multimorbidity’ used only 72 publications in their text from 1976 to 1990. Alone 66 of these 72 publications were written in German.

It was not until 1990 that concept received international attention through further research. Van den Akker defined multimorbidity, as the presence of multiple, recurrent, chronic or acute illness or symptoms within one person at the same time regardless of an underlying disease [18]. A complex structure with several individual diseases exists in multimorbidity and should always be considered as an independent phenomenon or as a specific disease state [17]. In contrast to comorbidity, there is no primary underlying disease in multimorbidity. While the term multimorbidity is structured patient-related and non-hierarchically oriented, comorbidity is disease-based and hierarchically oriented [7]. But, the terms are often used interchangeably or inconsistently in the literature [19]. As an example, a cardiologist may be concerned with the effect of comorbidity on the management of acute coronary syndromes, whereas multimorbidity captures the general complexity of patients without focusing on any single disease.

The World Health Organization (WHO) defines multimorbid patients than those who are affected by two or more medical or psychiatric conditions [6]. The intention of the WHO was to consider all the conditions of an individual that could affect the general health status. However, the term “state” is not defined clear enough for practical purposes (e.g. as whether the treated disease is a “state” in this sense) and could thus result in numerous interpretations [20].

The “European General Practice Research Network” conducted a systematic review of all relevant publications on this topic in 2011 and identified by more than 100 different definitions used by academic research. To find a comprehensive definition of multimorbidity, which is understandable and suitable for further joint research, the “European General Practice Research Network” asked the following two questions through a study: Which of the criteria for multimorbidity can be found in scientific publications medicine and what definition can be formulated using these criteria?

The criteria found were divided into 11 topics: chronic disease, acute illness, biopsychosocial factors and somatic risk factors, coping strategies of patients, disease burden, stress the health system, disability, quality of life, frailty, social network and health consequences. The “European General Practice Research Network” finally formulated a definition of multimorbidity, which was found in the common consensus: “ Multimorbidity is defined as any combination of chronic disease with at least one other disease (acute or chronic) or biopsychosocial factor (associated or not) or somatic risk factor. Any biopsychosocial factor, any somatic risk factor, the social network, the burden of diseases, the health care consumption, and the patient’s coping strategies may function as modifiers (of the effects of multimorbidity). Multimorbidity may modify the health outcomes and lead to an increased disability or a decreased quality of life or frailty”. This definition of “European General Practice Research Network” focused on the possible consequences of multimorbidity, such as health implications, disability, quality of life and frailty.

The above definition approaches to the definition of “geriatrics typical multimorbidity”. In addition to the presence of multiple co-existing chronic diseases, the disease pattern, the temporal evolution of the disease and social factors are important. In addition, geriatrics typical syndromes are (for example, such as incontinence, confusion, risk of falls and complex pain conditions), relevant to everyday life functional limitations and disabilities of patients [21]. According to the definition of the geriatric scientific society and the health insurance companies, a “typical geriatrics multimorbidity” exists if at least two of the following 14 geriatric syndromes coexist in a patient [22]:

  • immobility,

  • tendency to fall and vertigo,

  • cognitive impairment,

  • incontinence,

  • pressure ulcers,

  • malnutrition,

  • imbalance in fluid and electrolytes,

  • depression, anxiety disorders,

  • chronic pain,

  • paraesthesia,

  • reduced capacity,

  • strong visual and hearing impairment,

  • medication problems,

  • high risk of complications.

This geriatric syndromes again are symptoms or consequences of various diseases. For example, a reduced capacity could be the result of heart failure, chronic obstructive pulmonary disease or cancer. Thus, these criteria are different from the commonly used definitions that focus on individual diagnoses.

Comorbidity

The concept of comorbidity was preceded by the concept of multimorbidity. In the early seventies, Feinstein defined the term comorbidity as “[…] the existence or occurrence of any distinct additional entity during the clinical course of a patient who has the index disease under study”. As comorbidity he described the occurrence of an additional etiologically of the underlying disease (“index disease”) independent acute or chronic illness during the clinical course. The importance and impact of comorbidity for the entire clinical course of an underlying disease, in particular their treatment, care and prognosis, was thus recognized and described already in the seventies by Feinstein [23].

A further development of the concept of comorbidity for clinical problems was done based on the number and the nature of disease, the specification of the disease diagnosis by a physician or medical history of the patient and the location of the study survey, such as general practice centers, hospitals or nursing homes, during the seventies and eighties. Indices have been developed to investigate comorbidity in clinical studies [13]. However, these indices were based on different approaches. Charlson Comorbidity Index takes into account both the number and severity of the disease, to improve the prediction of 10-year mortality [24]. The “Index of coexistent Diseases” predicts health-related quality of life after surgery, while the Kaplan-Feinstein Index assesses comorbidity in patients with diabetes mellitus [12].

However, the general transferability of indexes is restricted, as some were derived from non-representative study populations and/or the underlying data sources (surveys, databases, network of general practice centers) are not comparable. According to a summary review by de Groot et al., the necessary methodological quality criteria are sufficiently met by only four indices: the Charlson Comorbidity Index, the “Cumulative Illness Rating Scale”, the “Index of Coexisting Disease” and the Kaplan-Feinstein Index [25]. Some of the above indices are used either for multimorbidity or comorbidity, depending on whether the focus is on the measurement of the total burden of disease in a patient or on the burden of comorbidities, which are in addition to an underlying disease [13]. The “Cumulative Illness Rating Scale” and Charlson Comorbidity Index are the summative indices, the Kaplan-Feinstein Index and the “Index of Coexisting Disease”, however ordinal indices. Here, the final score is the highest individual score [16]. Currently there is no consensus on the best method to measure comorbidity in research and clinical practice.

The studies that collected the comorbidity in general practice centers, hospitals or groups of patients or the population of a region, investigated the resulting consequences, such as mortality, physical function limitations, quality of life, treatment complications due to drug side effects, health care utilization, quality of care and cost. While the study survey on mortality was done mainly retrospective, cross-sectional and prospective studies were available on the effect on functional status and quality of life. In Germany, the National Health Survey of 1998 raised the disease patterns of comorbidity but also their impact and consequences such as quality of life, consequential costs and health-related quality of life at the population level. In a review of 82 studies from 1993 to 1997, the analysis of causes and consequences showed that comorbidity in almost all studies had influence on different survival parameters such as mortality, functional ability, quality of life and various aspects of health care utilization [6].

Frailty

Due to demographic changes and medical progress, the number of elderly and very elderly patients will increase with multiple illnesses in all areas of care. But multimorbidity in old age is more than the sum of individual diseases. Despite the problems caused by the individual diseases, symptoms such as incontinence, cognitive deficits, immobility, such as falls, pain and other complicating factors in elderly and very elderly patients also are added (see section “Multimorbidity”). Functional limitations and disabilities arise which affect the ability of older people to cope with everyday life. Multimorbidity therefore requires a comprehensive “functional” point of view in comparison with a view focused on the disease in the elderly. It is a very interesting concept when applied to elderly and very elderly patients, since it provides a comprehensive overview of all factors that could lead to frailty.

Frailty is an independent geriatric syndrome, which describes the state of the elderly, which is characterized by the reduced load capacity to external stressors [26]. Frailty is a reduction of physiological capacity, which is not confined to one organ system, but applies across multiple systems and also is not specifically linked to a single pathogenetic process [27]. According to Schuler and Oster, frailty is a state of reduced functional reserves. Important functional reserves of the individual are reduced by physiological and pathological alterations [28]. According to Fried, chronic malnutrition leads to sarcopenia with a loss of muscle strength, walking speed and decreasing physical activity. This can result in limitations to mobility, functional ability, incontinence and increased need for assistance or even death [29].

It is a construct that is difficult to diagnose in clinical practice [30]. According to Drey, a patient is defined as frail if it has weight loss, weakness, poor stamina, slowness, i.e. low walking speed, and low activity, i.e. reduced energy consumption [31]. Finally, there is a relationship between emerging multimorbidity, which can lead to frailty and then in turn to disability [32]. Frailty, an increase in disability or a decrease in quality of life, may therefore be the consequences of multimorbidity. These are factors that make physicians aware of multimorbidity for the first time in many of their older patients.

Methods of Measurement

Summation of Chronic Diseases

Multimorbidity is commonly known as the coexistence of two or more chronic diseases that refers to the simultaneous occurrence of two or more chronic diseases in a person [18]. Previous studies on multimorbidity reported two or more diseases simultaneously in 3.6 % up to 50 % of the patients in the Netherlands [33]. Van den Bussche defined multimorbidity as the presence of three or more diseases. He was able to demonstrate multimorbidity in 62.1 % of the patients examined in primary care in Germany [34]. The comparison of these studies is difficult because of their many differences in methodology, the population and the number and type of disease. Diederichs also pointed out that the boundaries between acute and chronic disease states are often blurred, so that a sharp separation not often succeeds between acute and chronic diseases. Therefore, the methodological approach is increasingly being questioned, to measure multimorbidity with a summation of chronic diseases. Other factors as social, emotional and psychological side effects should be also recorded as the occurrence of two or more diseases in the elderly is not uncommon [17].

Also Extermann criticized that the summation of chronic diseases in the research and clinical practice is not practical. The result is a vast amount of information, if any diagnosis and their severity is considered in the patient. Therefore, in his opinion, a selection and bundling of information is required. Indices reduce all diseases and their severity to a single numerical score. Thereby, a comparison with values from other patients is possible [16]. Until now, different strategies have been used to develop indices for multimorbidity. A first strategy is the qualitative “ad hoc” selection of cases for a particular study by clinical judgment. This strategy, however, is often not systematically performed and is not very reproducible. A second strategy includes a systematic categorical description of disease occurrence by defining criteria (e.g. ICD-9 codes). This can be further refined by each disease is assessed according to their status as active/inactive and/or of its impact on the probability of survival. The Charlson Comorbidity Index (see section “Charlson Comorbidity Index”) and the Kaplan-Feinstein Index (see section “Kaplan-Feinstein Index”) are indices applying this second strategy. Another strategy is the bundling of diseases accordingly involved organ systems in order to evaluate them within the systems. An example of this strategy is the “Cumulative Illness Rating Scale” (see section “Cumulative illness rating scale”) and the “Index of Coexisting Disease” (see section “Index of coexisting disease”) [35].

Charlson Comorbidity Index

The Charlson Comorbidity Index was developed by Mary Charlson and colleagues in 1987, based on data collected from breast cancer patients. It has been used in several studies to assess the severity of existing co-morbidities and is an easy to use instrument with which the general mortality risk can be estimated efficiently. The Charlson Comorbidity Index is used to predict the relative risk of dying of comorbidity factors within 10 years [24]. In addition to mortality, there were also significant relationships of the Charlson Comorbidity Index to disability, for resumption and length of stay in hospital [13]. It is - as the name suggests - rather a method to measure comorbidity than multimorbidity. In practice, however, it is often used for detection of the latter. The Charlson Comorbidity Index contains a list of 19 diseases that can be assessed with one to six points, depending on the severity (see Table 4.1). Any concomitant disease is associated depending on the risk of dying, with a score of one, two, three, or six. The score is added and the mortality rate can be predicted by the sum of the individual diseases (see Table 4.2). The research uses the Charlson Comorbidity Index in the classification of zero, one or two plus.

Table 4.1 List of 19 contributing diseases of the “Charlson Comorbidity Index”
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Table 4.2 Weighting of the “Charlson Comorbidity Index” for 19 contributing diseases
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The Charlson Comorbidity Index has the advantage that it is very clearly structured and easy to complete, since the criteria are easy to identify and differ from each other well. An advantage is that it can be determined without patient survey, so only with the help of the medical record, and only slightly takes time for gathering and analyzing data (about 5 minutes). The index can be optionally used with and without age correction, and is validated for oncology patients. The Charlson Comorbidity Index has now been adapted to the use of administrative data (e.g. ICD-9 codes) [36, 37]. It is characterized by a very good reliability, excellent correlation with mortality and progression-free survival. The test-retest reliability, i.e. the degree of consistency of test results in the same subjects and with the same test in several testings, is good and the inter-rater reliability, i.e. the extent of the consistency of assessment results for different observers, is moderate to good [13]. A limitation of the index is that it only interrogates nineteen diseases. It does not take account of non-malignant hematological diseases (e.g. anemia).

Cumulative Illness Rating Scale

Another methodological approach to measure multimorbidity is the “Cumulative Illness Rating Scale” [38]. The “Cumulative Illness Rating Scale” aims to detect the physical deterioration of the patient by the estimated damage of 13 body systems using a five-point severity scale [25]. The “Cumulative Illness Rating Scale” was developed to assess the total medical burden and capacity for elderly patients to survive and was not originally designed as a comorbidity index [16]. Miller and colleagues revised the “Cumulative Illness Rating Scale” to take account of the problems of the elderly in long-term care. In 1992, they renamed the index in “Cumulative Illness Rating Scale for Geriatrics”, abbreviated CIRS-G [39]. This quantitative scale is used to detect the state of health of institutionalized frail older adults. Based on the examination of the patient and the available document, the doctor or nurses evaluate each of 14 organ systems, whether and to what extent it is affected by damage, malfunctions and activity impairment (see Table 4.3).

Table 4.3 “Cumulative illness rating scale”
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The 14 organ systems include heart, high blood pressure and vascular, hematopoietic and lymphatic system, lungs and respiratory tract (below the larynx), eye and ear, nose and throat medicine (eyes, ears, nose, pharynx, larynx), upper gastrointestinal tract (esophagus, stomach, duodenum, without a pancreas), the lower gastrointestinal tract (lower digestive tract, hernia), liver, gall bladder and pancreas, kidneys (without urinary tract, bladder and prostate), urogenital tract (ureters, urinary bladder, urethra, prostate, genital organs, uterus, ovaries), musculoskeletal and skin, nervous system (brain, spinal cord, nerves, and without dementia and depression), endocrine, metabolic disorders and breast disorders (including various infectious diseases and poisoning) and mental disorders (including dementia and depression). The rating is intuitive and is based on the description of the rating criteria from zero to four (see Table 4.4).

Table 4.4 Weighting of 14 for “Cumulative Illness Rating Scale” contributing organ systems
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The end result of “Cumulative Illness Rating Scale” is the sum of each of the 14 individual organ systems score. The scale can vary theoretically between zero and 56 points, although a very high score is impossible because it would represent multiple organ system failures that are not compatible with life [40].

“Cumulative Illness Rating Scale” has good interrater reliability with correlation coefficients in the range from 0.55 to 0.91 [41]. The retest reliability is good [13]. Some studies have also documented a good predictive validity for mortality and autopsy [42–44]. One study showed a significant association with the risk of hospitalization in the following year [41]. Another study reported good discriminant validity, i.e. the measurements differ from each other by different constructs [39]. “Cumulative Illness Rating Scale” is one of the few validated instruments that can be used to quantify the multimorbidity in research [45]. Before using the “Cumulative Illness Rating Scale” it should however be reviewed to what extent the design of a planned study corresponds to the original study population of the index [16].

Index of Coexisting Disease

The “Index of Coexisting Disease” was first developed in 1993 by S. Greenfield to assess comorbidity in patients with malignant tumors (see Table 4.5). Later, the “Index of Coexisting Disease” was used for other patient categories. This method helps in calculating the length of stay of a patient in the hospital and the risks of repeated reception thereof in the hospital after surgery. For the assessment of comorbidity, the “Index of Coexisting Disease” evaluated separately the patient’s condition by two different components: Physiological and functional properties. The first component – “Index of Disease Severity” – measures the severity of sixteen concomitant diseases, each of which is rated on a 4-point scale, with zero being the absence of disease and three indicating the most severe form of the disease (see Table 4.6).

Table 4.5 “Index of Coexisting Disease” with its two components: “Index of Disease Severity” and “Index of Physical Impairment”
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Table 4.6 Weighting of the “Index of Disease Severity” [46]
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The second component – “Index of Physical impairment” – focuses on the co-morbidity caused by the functional restrictions. It assesses eleven defined functional areas with a 3-point scale, where zero means normal functionality and two repealed functionality (see Table 4.7).

Table 4.7 Weighting of the “Index of Physical Impairment” [46]
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Various data support the predictive validity of the “Index of Coexisting Disease”. The intrarater reliability, i.e. the extent of the consistency of assessment results for the same observers, is good, while the inter-rater reliability is moderate [13]. A limitation of the “Index of Coexisting Disease” is the exclusion of psychiatric elements. Alcoholism per se is not queried by the “Index of Coexisting Disease” and an affected patient would only have positive points if he had known liver disease [16].

Kaplan-Feinstein Index

The Kaplan-Feinstein Index was developed in 1974 as a scheme for the classification of comorbidity and their prognostic relevance in terms of 5-year mortality in patients with diabetes mellitus. The index includes twelve comorbidities that may affect the long-term survival of the patient (see Table 4.8). They are each divided into four severity levels from zero (no disease) to three (severe disease). Grade three is evaluated for a state after decompensation or recently undergone life-threatening episodes caused by the respective comorbidity. Degree two describes a restriction, but not yet complete decompensation and degree one is a slight or implied decompensation or chronic disease. The Kaplan-Feinstein Index in 1986 was tested on patients with prostate cancer and in 1995 on patients with head and neck cancer. A correlation of limitation in overall survival was observed. Unique about this score is that it contains a weighting for each comorbidity of zero to three and the final score corresponds to the highest individual score, and not the sum of the individual ratings. The maximum score is thus three and thus comparatively low. If it is judged twice with the score two in the individual factors that endpoint number also remains at three. Meanwhile, the Kaplan-Feinstein Index for MMCI- and ACE-27 index was developed [16]. Accurate data on the validity or reliability are not known [13].

Table 4.8 The “Kaplan-Feinstein Index”
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Consequences of Multimorbidity

Patients with multimorbidity have on average a lower quality of life, increased mental stress, and longer hospital stays than patients without multimorbidity. They are at heightened risk of adverse health outcomes, often beyond the effects of the individual conditions. These include death, functional limitation and disability, frailty, nursing home placement, treatment complications, and avoidable inpatient admissions. Multimorbid patients experience health care uncoordinated and evaluate the quality worse than patients without multimorbidity. The cost of health care increases exponentially with the number of diseases, in particular due to the increasing number of outpatient visits and hospitalizations. Drug treatment of multimorbid patients has other consequences: multimorbidity is counted among the strongest predictors of multi-drug/polypharmacy. It is estimated that about 6.5 % of all hospital admissions are due to adverse drug events. Since older people have a reduced tolerance for drugs, they are particularly affected.

Most treatments and practice guidelines traget a single index condition, but patients with multimorbidity are complex and heterogeneous. The traditional disease-focused approach to clinical medicine may render care that is fragmented an poorly coordinated and produce treatment plans that are inefficient, ineffective, or even harmful for patients with multimorbidity. Currently, clinicians have limited guidance or evidence on which to base care decisions for such patients.

Conclusion

This capital describes that first, there are no universal consensus on the definition of multimorbidity in the current literature. In addition, multimorbidity is often used in research and clinical practice synonymous with the term comorbidity and/or the connotations of multimorbidity and comorbidity are mixed [13]. Multimorbidity defined Van den Akker generally as the presence of multiple, recurrent, chronic or acute illness or symptoms within one person at the same time regardless of an underlying disease [18]. In particular, for specific populations such as the elderly, this definition is however insufficient because the disease pattern, the temporal development of disease, social factors but also geriatrics typical syndromes (such as incontinence, confusion, risk of falls and complex pain conditions), relevant to everyday life functional limitations and disabilities are of great importance. Frailty is a consequence of multimorbidity in these elderly patients. Many of the doctors are first made aware of the occurrence of frailty on multimorbidity in many of their older patients. The recently, in this sense revised definition of multimorbidity of the “European General Practice Research Network” moves into the center the possible consequences of multimorbidity for the patient, such as health consequences, disability, quality of life and frailty [20].

Second, there is no generally accepted “gold standard” for measuring multimorbidity. While the accumulation of chronic diseases in the research and clinical practice is not very practical because of the lack of comparability of methods and the resulting amounts of information, indexes reduce all diseases and their severity to a single numerical score, making possible a comparison with values from other patients [16]. According to a survey by de Groot only four met by the large number of available indexes sufficiently the necessary methodological quality criteria: the Charlson Comorbidity Index, the “Cumulative Illness Rating Scale”, the “Index of Coexisting Disease” and the Kaplan-Feinstein Index [25].

Third, the general transferability of indices between different populations is restricted, as some were derived from non-representative study populations and/or the underlying data sources (surveys, databases, network of general practice) are not comparable with each other.

Fourth, multimorbidity is associated with poor health outcomes and significant healthcare expenditures.

The challenges of managing patients with multimorbidity are multiple, including the lack of guidelines that are applicable to these complex patients and the conflicting recommendations that arise in trying to apply guidelines developed for single disease conditions; competing and shifting patient priorities of conditions to be addressed; the risks associated with polypharmacy; and the lack of evidence on how best to treat patients with specific comorbid illnesses.

Principles of caring for patients with multimorbidity include attention to understanding a patients goal of treatment and healthcare priorities; communication between multiple providers, healthcare facilities, and caregivers involved in a patient’s treatment; recognizing the potential harms associated with medical interventions and minimizing drug dosing and complexity; and identifying and addressing lifestyle and psychosocial issues that may affect the patient’s quality of life and response to medial care