The authors have declared that no competing interests exist.
Conceived and designed the experiments: ACL APT. Performed the experiments: ACL BPP JMAD APF APT. Analyzed the data: BPP. Contributed reagents/materials/analysis tools: ACL LGF FGR MLS APT. Wrote the manuscript: ACL LGF FGR MLS APT.
The aim of this study was to demonstrate the existence of systematic associations in drug prescription that lead to the establishment of patterns of polypharmacy, and the clinical interpretation of the associations found in each pattern.
A cross-sectional study was conducted based on information obtained from electronic medical records and the primary care pharmacy database in 2008. An exploratory factor analysis of drug dispensing information regarding 79,089 adult patients was performed to identify the patterns of polypharmacy. The analysis was stratified by age and sex.
Seven patterns of polypharmacy were identified, which may be classified depending on the type of disease they are intended to treat: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. Some of these patterns revealed a clear clinical consistency and included drugs that are prescribed together for the same clinical indication (i.e., ARI and COPD patterns). Other patterns were more complex but also clinically consistent: in the cardiovascular pattern, drugs for the treatment of known risk factors—such as hypertension or dyslipidemia—were combined with other medications for the treatment of diabetes or established cardiovascular pathology (e.g., antiplatelet agents). Almost all of the patterns included drugs for preventing or treating potential side effects of other drugs in the same pattern.
The present study demonstrated the existence of non-random associations in drug prescription, resulting in patterns of polypharmacy that are sound from the pharmacological and clinical viewpoints and that exist in a significant proportion of the population. This finding necessitates future longitudinal studies to confirm some of the proposed causal associations. The information discovered would further the development and/or adaptation of clinical patient guidelines to patients with multimorbidity who are taking multiple drugs.
Multimorbidity, which is defined as suffering from multiple chronic diseases simultaneously, has begun to be considered a major health problem affecting developed countries [
Drug therapy is an area in which this shortage of available evidence is most clearly manifested since the use of multiple disease-focused CPGs might lead to misinterpretations by GPs. In fact, polypharmacy has frequently undesirable consequences, such as increased risk of inappropriate drug use, under-use of effective treatments, medication errors, poor adherence, drug-drug and drug-disease interactions and, most importantly, adverse drug reactions [
According to the European Forum for Primary Care, an important step in producing and/or adapting the available evidence to patients with multimorbidity lies in the consideration of the systematic associations between diseases and drugs [
The general objective of this paper is to show the existence of systematic associations in drug prescription and use, which create patterns of polypharmacy. The specific objectives are 1) to describe drugs that constitute these patterns, 2) to estimate the prevalence of these patterns, and 3) to interpret clinically the associations found in each pattern.
A cross-sectional study was conducted based on data obtained from electronic medical records and pharmacy billing records for 79,089 patients who were over 14 years of age and had been seen at least once by their family doctor in 2008. The seven Zaragoza health centres that were included in the study were previously selected based on criteria related to the quality of the collected information [
Demographic variables of the age and sex were extracted from patients’ electronic medical records. Data on prescribed and dispensed active ingredients during 2008, and the date of dispensing was obtained from the pharmacy billing records. The active ingredients were coded according to the Anatomical Therapeutic Chemical Classification System (ATC) [
This study was favourably evaluated by the Clinical Research Ethic Committee of Aragon (CEICA). Written consent by patients was not needed since the study does not involve interventions on individuals, the use of human biological samples, or the analysis of personally identifiable data. Instead, the present work is based on the statistical analysis of anonymous data contained in previously existing databases which were obtained with prior permission from the corresponding entity.
All of the analyses were stratified by sex and age; the latter variable was grouped into three intervals: 15-44, 45-64, and ≥64. The identification of patterns of polypharmacy was based on exploratory factor analysis, which is one of the methods commonly used to identify patterns of multimorbidity [
The factor analysis was based on a tetrachoric correlation matrix, and the factor extraction was performed using the principal factor method. The number of factors to extract was determined using sedimentation graphs (Figure A in
To estimate the prevalence of the individual patterns of polypharmacy, the number of individuals who had a certain pattern was determined, considering that an individual belonged to the pattern if he/she had been dispensed at least three of the drugs included in the pattern. It is understood that the threshold of three drugs dispensed simultaneously could justify, by itself, some of the undesirable effects of polypharmacy [
The STATA 11.0 software was used for the statistical analyses.
The study population was composed of 79,089 patients who were over 14 years of age (with a mean age of 47 years), of which 55.03% were women (
18,779 (23.74) | 13,807 (17.46) | 12,016 (15.19) | 15,341 (19.4) | 10,725 (13.56) | 8,418 (10.64) | |
230 (1.22) | 2,347 (17) | 6,154 (51.22) | 324 (2.11) | 2,333 (21.75) | 3,709 (44.06) | |
150 (0.8) | 718 (5.2) | 1,986 (16.53) | 170 (1.11) | 1,076 (10.03) | 1,666 (19.79) | |
316 (1.68) | 1,903 (13.78) | 2,095 (17.44) | 646 (4.21) | 1,879 (17.51) | 1,382 (16.42) | |
20 (0.11) | 42 (0.3) | 74 (0.62) | 13 (0.08) | 93 (0.87) | 178 (2.11) | |
2 (0.01) | 59 (0.43) | 270 (2.25) | 13 (0.08) | 149 (1.39) | 314 (3.73) | |
3 (0.02) | 22 (0.16) | 287 (2.39) | 5 (0.03) | 31 (0.29) | 160 (1.9) | |
1,591 (8.47) | 1,437 (10.41) | 933 (7.76) | 731 (4.77) | 506 (4.72) | 279 (3.31) | |
571 (3.04) | 1,003 (7.26) | 857 (7.13) | 233 (1.52) | 307 (2.86) | 218 (2.59) | |
437 (2.33) | 482 (3.49) | 533 (4.44) | 262 (1.71) | 225 (2.1) | 240 (2.85) | |
--- | 15 (0.11) | 82 (0.68) | --- | 11 (0.1) | 73 (0.87) | |
640 (3.41) | 830 (6.01) | 1,127 (9.38) | 494 (3.22) | 554 (5.16) | 856 (10.17) | |
16 (0.09) | 102 (0.74) | 231 (1.92) | 18 (0.12) | 240 (2.24) | 744 (8.84) | |
711 (3.79) | 346 (2.51) | 175 (1.46) | 496 (3.23) | 184 (1.72) | 124 (1.47) | |
439 (2.34) | 328 (2.38) | 346 (2.88) | 336 (2.19) | 125 (1.17) | 111 (1.32) | |
21 (0.11) | 769 (5.57) | 1,227 (10.21) | 8 (0.05) | 30 (0.28) | 77 (0.91) | |
10,094 (53.75) | 3,977 (28.8) | 856 (7.12) | 9,788 (63.8) | 3,856 (35.94) | 821 (9.75) | |
2,989 (15.92) | 1,931 (13.99) | 574 (4.78) | 2,129 (13.88) | 1,614 (15.04) | 709 (8.42) | |
2,574 (13.71) | 1,939 (14.04) | 951 (7.91) | 1,712 (11.16) | 1,572 (14.65) | 919 (10.92) | |
3,122 (16.62) | 5,960 (43.18) | 9,635 (80.19) | 1,712 (11.17) | 3,686 (34.36) | 5,969 (70.91) |
Seven patterns of polypharmacy were identified in this study, which, depending on the type of disease they are intended to treat, may be classified as cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. The first four patterns occurred in both men and women, the following two occurred only in men, and the latter occurred only in women (
Depression-anxiety | 0.53 | Depression-anxiety | 11.90 | Depression-anxiety | 37.48 | |
ARI | 8.39 | Cardiovascular | 3.62 | Cardiovascular | 8.85 | |
ARI | 7.39 | COPD | 7.41 | |||
Menopause | 0.55 | |||||
Depression-anxiety | 0.78 | Depression-anxiety | 2.04 | Depression-anxiety | 0.29 | |
ARI | 3.55 | Cardiovascular | 10.85 | Cardiovascular | 24.63 | |
Rhinitis-asthma | 0.09 | COPD | 5.18 | COPD | 25.34 | |
Pain | 4.52 |
* Numerator: individuals with three or more drugs of the pattern within each age and sex group; Denominator: the entire population within each age and sex group.
A clear clinical consistency was identified in some of these patterns because they encompassed various therapeutic groups with a common clinical indication—as was the case for the ARI or COPD patterns. Other patterns were more complex but also clinically consistent; this was the case of the cardiovascular pattern, which included medications for the treatment of known risk factors (i.e., diabetes, hypertension, or dyslipidemia) along with other medications aimed at preventing complications (e.g., antiplatelet agents). Finally, this study also discovered associations that are difficult to explain based on the available clinical knowledge and that should facilitate the design of future research efforts.
The various identified patterns of polypharmacy are analysed in detail below.
The cardiovascular pattern is present in men and women from age 45 years onwards (
Ace inhibitors, plain | Ace inhibitors, plain | ||
Angiotensin ii antagonists, combinations | Antigout preparations | ||
Angiotensin ii antagonists, plain | Antithrombotic agents | ||
Antiglaucoma preparations and miotics | Beta blocking agents | ||
Antithrombotic agents | Blood glucose lowering drugs, excluding insulins | ||
Beta blocking agents | Cardiac glycosides | ||
Blood glucose lowering drugs, excluding insulins | High-ceiling diuretics | ||
High-ceiling diuretics | Insulins and analogues | ||
Insulins and analogues | Potassium-sparing agents | ||
Lipid modifying agents, plain | Selective calcium channel blockers with direct cardiac effects | ||
Selective calcium channel blockers with mainly vascular effects | Vasodilators used for cardiac diseases | ||
Ace inhibitors, plain | Ace inhibitors, plain | ||
Angiotensin ii antagonists, combinations | Antithrombotic agents | ||
Angiotensin ii antagonists, plain | Beta blocking agents | ||
Antigout preparations | Drugs for peptic ulcer and gastro-oesophageal reflux disease | ||
Antithrombotic agents | High-ceiling diuretics | ||
Beta blocking agents | Insulins and analogues | ||
Blood glucose-lowering drugs, excluding insulins | Lipid modifying agents, plain | ||
Drugs for peptic ulcer and gastro-oesophageal reflux disease | Potassium-sparing agents | ||
High-ceiling diuretics | Selective calcium channel blockers with direct cardiac effects | ||
Insulins and analogues | Selective calcium channel blockers with mainly vascular effects | ||
Lipid modifying agents, plain | Vasodilators used in cardiac diseases | ||
Selective calcium channel blockers with mainly vascular effects | |||
Vasodilators used in cardiac diseases |
After 65 years of age, the prevalence of this pattern increases in women, being present in almost one out of ten. In addition, new drugs are added as possible treatments for some of the complications in these patients, such as nitrites for ischaemic heart disease, digoxin and aldosterone inhibitors for heart failure, and hypouricemic drugs, which are frequently prescribed for cardiovascular disease [
In men who are 45 to 64 years of age, the pattern almost triples in prevalence compared with women (11%) and is very similar in terms of its composition. This greater prevalence of the pattern is consistent with the increased frequency of cardiovascular disease in men. Other relevant differences with regard to women are as follows: nitrites are used in ischaemic heart disease, which occurs earlier in men; hypouricemic drugs begin to be used; and PPIs appear, which could be associated with the use of antiplatelet agents in patients for whom these drugs are indicated in the CPGs [
During old age, after 65 years, the prevalence of this pattern of polypharmacy increases until it is present in one out of four men. Regarding the therapeutic groups that comprise this pattern, there are three important differences compared with women of the same age: 1) the sustained use of PPIs, 2) the absence of drugs for heart failure, and 3) the additional use of lipid-lowering drugs. The latter difference may be due to an increased cardiovascular risk in men and their increased incidence of ischaemic heart disease and cerebrovascular disease—with the effectiveness of lipid-lowering drugs being less evident in women [
In summary, this study allowed for the identification of a clinically consistent cardiovascular pattern of polypharmacy that exhibits a clear relation to the recently described cardio-metabolic multimorbidity pattern (2) and that develops differently based on the gender and age. The present investigation also revealed the presence of unexpected associations (i.e., antiglaucoma drugs in middle-aged women) or the absence of certain drugs (such as PPIs) in older women, which opens new and relevant research areas.
This is a highly prevalent pattern, present in all age and gender groups, with a wide range of variation in their composition and frequency of occurrence (i.e., at advanced ages, the frequency ranges between 37% in women and 0.3% in men) (
Antiandrogens | Antacids | Antidepressants | |
Antidepressants | Antidepressants | Antiepileptics | |
Antiepileptics | Antiepileptics | Antiinflammatory and antirheumatic products, non-steroids | |
Antipsychotics | Antiinflammatory and antirheumatic products, non-steroids | Anxiolytics | |
Anxiolytics | Antipsychotics | Calcium | |
Muscle relaxants, centrally acting agents | Anxiolytics | Drugs for peptic ulcer and gastro-oesophageal reflux disease | |
Drugs for peptic ulcer and gastro-oesophageal reflux disease | Iron preparations | ||
Hypnotics and sedatives | Laxatives | ||
Laxatives | Opioids | ||
Muscle relaxants, centrally acting agents | Other urologicals, including antispasmodics | ||
Opioids | Other analgesics and antipyretics | ||
Propulsives | Propulsives | ||
Psychostimulants, agents used for ADHD and nootropics | |||
Topical products for joint and muscular pain | |||
Vitamin B12 and folic acid | |||
Antidepressants | Antacids | Agents for treatment of haemorrhoids and anal fissures for topical use | |
Antiepileptics | Antidepressants | Antidepressants | |
Antipsychotics | Antiepileptics | Antipsychotics | |
Anxiolytics | Antipsychotics | Capillary stabilising agents | |
Drugs for peptic ulcer and gastro-oesophageal reflux disease | Anxiolytics | Cardiac glycosides | |
Lipid modifying agents, plain | Hypnotics and sedatives | Dopaminergic agents | |
Laxatives | Laxatives | ||
Opioids | |||
Propulsives |
Despite the clinical coherence in most of the associations between drugs, other associations were detected, for which it has not been possible to find a causal explanation. This is the case of antiandrogens (i.e., ethinyloestradiol and cyproterone) in young women aged 15 to 44 years, although future studies should continue to shed light on the possible association between acne beginning at puberty and depression [
In young men aged 15 to 44 years, lipid-lowering medications and drugs for peptic ulcer and gastro-oesophageal reflux are added to the pattern. The presence of the latter medications could be justified because of the association between antidepressants and upper gastrointestinal tract bleeding [
Among patients aged 45 to 64 years, opioids are added to this pattern, which may be explained by the association for depression-somatisation pain [
After 65 years of age, this pattern of polypharmacy corresponds to a clinical situation of serious mental illness and it includes antidepressants, anxiolytics, and anticonvulsants in women as well as antidepressants, antipsychotics, and dopaminergic agents in men. Furthermore, in women, an analgesic component appears in this pattern, which consists of the same drug groups as that for middle-aged women (e.g., opioids) and topical preparations for joint pain. The use of laxatives and gastroprokinetic agents is present in both sexes, most likely in response to the adverse effects of opioids [
In men over 65 years of age, it is possible to hypothesise that this pattern relates to the treatment of psychogeriatric diseases, comprising dopaminergic agents prescribed for parkinsonism, in addition to the previously mentioned drugs [
In conclusion, some of the findings within this complex pattern indicate associations between drugs that are difficult to explain from the available clinical knowledge. It has also been impossible to elucidate the causes of certain differences observed between the sexes, such as the absence of antipsychotics in older women or the absence of vitamin B12 and folic acid in older men.
This pattern is present in men from 15 to 44 years of age and in women up to 64 years (
Adrenergics, inhalants | Adrenergics, inhalants | ||
Antifungals for topical use | Antihistamines for systemic use | ||
Antihistamines for systemic use | Antiinfectives for systemic use | ||
Antiinfectives and antiseptics, excluding combinations with corticosteroids | Corticosteroids for systemic use, plain | ||
Antiinfectives for systemic use | Cough suppressants, excluding combinations with expectorants | ||
Antiinflammatory and antirheumatic products, non-steroids | Decongestants and other nasal preparations for topical use | ||
Anxiolytics | Expectorants, excluding combinations with cough suppressants | ||
Corticosteroids, plain | Nasal decongestants for systemic use | ||
Cough suppressants, excluding combinations with expectorants | Other analgesics and antipyretics | ||
Decongestants and other nasal preparations for topical use | |||
Drugs for peptic ulcer and gastro-oesophageal reflux disease | |||
Expectorants, excluding combinations with cough suppressants | |||
Opioids | |||
Other analgesics and antipyretics | |||
Antiinfectives for systemic use | |||
Antiinflammatory and antirheumatic products, non-steroids | |||
Cough suppressants, excluding combinations with expectorants | |||
Drugs for peptic ulcer and gastro-oesophageal reflux disease | |||
Expectorants, excluding combinations with cough suppressants | |||
Other analgesics and antipyretics |
In middle-aged women, the prevalence of this pattern is very similar to that in young women (7%), but with interesting therapeutic absences: 1) NSAIDs, perhaps due to underprescribing because of the risk of digestive and cardiovascular side effects (consequently, PPIs also do not appear); 2) antifungals for topical use, most likely due to the lower incidence of vaginal candidiasis in postmenopausal women [
Between 15 and 44 years of age, the prevalence of this pattern in men is one-half that in women of the same age (4%) and comprises analgesics, NSAIDs with their associated PPIs, antibiotics, and drugs for the symptomatic treatment of cough. With respect to women of the same age, opioids, sympathomimetic bronchodilators, nasal decongestants, and the previously discussed therapeutic groups of difficult clinical explanation disappear.
In summary, the ARI pattern is highly prevalent—probably due to the use of pharmacy data from the months of January and February—and comprises a group of drugs administered for the same category of diseases, including medications (e.g., vaginal antifungal agents and PPIs) that are used to treat complications of these illnesses or the side effects of other drugs. Some of the associations that have been found, especially in young women, should be further investigated.
The COPD pattern appears in men over 44 years of age, and it is delayed in women until the age of 65 years (
Adrenergics, inhalants | |||
Antihistamines for systemic use | |||
Antiinfectives | |||
Antiinfectives for systemic use | |||
Antiinfectives for systemic use | |||
Antiinflammatory agents and antiinfectives in combination | |||
Corticosteroids for systemic use, plain | |||
Cough suppressants, excluding combinations with expectorants | |||
Decongestants and other nasal preparations for topical use | |||
Expectorants, excluding combinations with cough suppressants | |||
Other drugs for obstructive airway diseases, inhalants | |||
Adrenergics, inhalants | Adrenergics, inhalants | ||
Antihistamines for systemic use | Antihistamines for systemic use | ||
Antiinfectives for systemic use | Antiinfectives | ||
Corticosteroids for systemic use, plain | Antiinfectives for systemic use | ||
Cough suppressants, excluding combinations with expectorants | Antiinflammatory agents and antiinfectives in combination | ||
Decongestants and other nasal preparations for topical use | Antiinflammatory and antirheumatic products, non-steroids | ||
Expectorants, excluding combinations with cough suppressants | Antiinflammatory agents | ||
Other analgesics and antipyretics | Calcium | ||
Other drugs for obstructive airway diseases, inhalants | Corticosteroids for systemic use, plain | ||
Cough suppressants, excluding combinations with expectorants | |||
Drugs for peptic ulcer and gastro-oesophageal reflux disease | |||
Expectorants, excluding combinations with cough suppressants | |||
Opioids | |||
Other drugs for obstructive airway diseases, inhalants | |||
Other analgesics and antipyretics | |||
Other ophthalmologicals |
In men over 64 years of age, this pattern is present in one out of four individuals and comprises the same drugs that are used by middle-aged individuals, to which NSAIDs and drugs for peptic ulcer and gastro-oesophageal reflux are added. The presence of calcium in this pattern is possibly due to its use for the prevention of osteoporosis in patients taking corticosteroids. Opioids also appear, prescribed probably as antitussives or analgesics in patients with COPD [
In older women, this pattern has a prevalence of 7% and exhibits certain peculiarities, namely, the absence of opioids, eye lubricants, and calcium. It is necessary to consider what the possible causes are. Finally, it should be mentioned that PPIs, which are prescribed for protection against NSAIDs or the gastric reflux induced by beta-2 mimetics, do not appear to be associated to this pattern among women.
The rhinitis-asthma pattern occurs with a low frequency and exclusively in young men (0.1%), and it is highly consistent from the clinical viewpoint (
Adrenergics, inhalants | |||
Antihistamines for systemic use | |||
Decongestants and other nasal preparations for topical use |
The pain pattern appears only in men who are 45 to 64 years of age, affecting 5% of the patients in this group (
Antiinflammatory and antirheumatic products, non-steroids | |||
Cough suppressants, excluding combinations with expectorants | |||
Drugs for peptic ulcer and gastro-oesophageal reflux disease | |||
Low-ceiling diuretics, excluding thiazides | |||
Muscle relaxants, centrally acting agents | |||
Opioids | |||
Other analgesics and antipyretics | |||
Topical products for joint and muscular pain |
The menopause pattern has a low prevalence—1% of women aged 45-64 years-(
Calcium | |||
Decongestants and antiallergics | |||
Drugs affecting bone structure and mineralisation | |||
Oestrogens | |||
Other ophthalmologicals | |||
The main strengths of the present study are the large population size and the quality of the data in the pharmacy database (i.e., pharmacy billing records), which yield greater reliability and representativeness compared with other studies that are based on medical records or surveys of drug use [
The exploratory factor analysis that was employed in this study, in addition to being the technique that best responds to the proposed objective, was performed according to the recommendations of Costello et al. [
Although several hypotheses have been presented regarding the pathophysiological processes that underlie the seven polypharmacy patterns revealed in this study, the former must be interpreted with the necessary caution since the study design (i.e., transversal) does not allow for the establishment of the sequence in which medications cluster within a pattern. Longitudinal studies would be necessary to corroborate the suggested causal associations and to elucidate those associations that could not be explained in the present study.
Another limitation of this study stems from the lack of information on the actual use of drugs by the patients because the pharmacy database contains information on the drugs that are prescribed and dispensed at the pharmacy, without providing proof of their consumption. Yet, this is currently the data source of choice when carrying out population-based studies on drug use, as stated previously.
Access to data on the use of over-the-counter (OTC) medications was not available, which could lead to an underestimation of the actual drug utilisation. Additionally, only patients seen by their GP in 2008 were included in the study. By doing so, prevalence figures of polypharmacy patterns may overestimate the real frequency in the studied age and sex groups. However, we believe this drawback may not have interfered with the essential objective of the study, that is, to analyse systematic associations in drug prescription and use.
Because these data were obtained from seven different health centres, there may be differences in the socioeconomic status and/or accessibility to public health care among members of the target population; however, this heterogeneity across individuals would increase the external validity of the results. Some variability might also exist between the centres in the drug prescription practices of their health professionals, which would directly influence the results. Similarly, potential differences in the organisational or functional aspects of each centre (e.g., organisation of the pharmacy or laboratory) could indirectly influence the associations obtained. Therefore, the fact that the therapeutic group variable has been analysed with the information obtained up to the third level of the ATC classification (i.e., by the therapeutic family rather than by the active ingredient) would reduce the possible variability between the centres and professionals in determining the patterns of polypharmacy.
No distinction was made regarding the level of care where prescriptions originated albeit the importance of induced prescription in primary care, as stated in the introduction. Future studies should consider this information in order to elucidate the impact of the primary-secondary care interface on the nature and intensity of polypharmacy.
Comparing our results with those of other studies is difficult, mainly because of the lack of similar studies in the scientific literature. In fact, the present study is the first investigation of the patterns of polypharmacy to be conducted in the general population. Research in the field of pharmacoepidemiology remains driven by the hermetic single-disease-single-medication framework required in clinical trials [
This study revealed systematic associations in drug prescription that affect a significant proportion of the population and that are present in all of the age and sex groups that were studied. These associations yield patterns of polypharmacy that are consistent from the pharmacological and clinical points of view. Seven patterns of polypharmacy were identified: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause.
The clinical interpretation of the relations between the drugs that give rise to these patterns allows us to hypothesise the existence of underlying causal factors that are often related, not to the disease itself, but to the adverse effects of the prescribed treatments, which would explain many of the observed associations.
The present study highlights the necessity of developing future longitudinal studies, including the joint analysis of diseases and drugs, which would facilitate the validation of certain potential interactions described in this article. This information would be an essential source for the development of CPGs addressing multimorbidity and the design of clinical management strategies and models of care with the capacity to respond appropriately to the real health needs of patients with multiple chronic conditions.
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