Although this systematic review confirms the inverse relationship between multimorbidity and QOL, it also raises some important questions. First, the relative lack of studies in primary care evaluating the association between multimorbidity and QOL or HRQOL is surprising given the number of patients who suffer from multiple concurrent chronic conditions. Although the existence of this association makes logical sense, it still has to be demonstrated and thoroughly studied to find ways of improving care for specially affected patients. Thus, the pressing question may not be whether there is an association but rather how strong is the association and what factors are responsible for it? Identifying these factors may contribute to better care for the affected patients. There is a clear need for further studies to address these issues.
Ultimately, multimorbidity has the potential to affect all domains of QOL. However, the influence of multimorbidity on the social and psychological dimensions of QOL is much less clear than its influence on the physical domains. It is noteworthy that several studies showed a significant decline in social and psychological dimensions of QOL in patients with 3, 4, or more concurrent diagnoses. What does this finding mean? Is there any bias that can explain this difference, or is it related to a certain capacity for adaptation? Are there other factors associated with this finding? All of these questions have yet to be answered.
All the studies examined were cross-sectional in nature. The effect of multimorbidity may vary over time. Some medical conditions may improve while others worsen resulting in various effects on QOL. Therefore, cross-sectional studies may not capture the real effect of multimobidity on QOL and predict the direction of change over time.
Defining and measuring multimorbidity
The absence of a uniform way of defining and measuring multimorbidity is of special concern and may explain some of the variability in our results. In most of the studies we evaluated, investigators had used only a simple list of diseases to identify concurrent medical conditions in patients, providing very incomplete information. Furthermore, the numbers and types of medical conditions in these lists varied among the studies, precluding comparisons.
Given the urgent need for conceptual clarity, Van den Akker and colleagues' definition of multimorbidity should be refined and advanced to achieve a common understanding. A distinction must be made between simple and complex chronic diseases. Treated hypothyroidism (simple) and ischemic heart disease (complex) obviously do not have the same impact on QOL. Moreover, the influence of single-organ versus multi-organ diseases needs to be appropriately weighed. Additional factors to be considered when defining multimorbidity include the severity of the conditions and the presence or absence of associated pain.
The use of self-reported diagnoses in many studies is another methodological limitation that may have introduced error. Patients may confuse symptoms and minor ailments with more significant disease states or may forget to report important diagnoses that are still active. Self-reporting may even be completely inaccurate in the presence of psychosomatic disorders. Conducting a chart review, clinical interview or using any specific standardized method may be a better way to obtain data related to diagnoses.
Another methodological limitation of most of the studies evaluated was their failure to consider the influence of psychiatric comorbidity. This was either because psychiatric diagnoses were not included in the lists of disease states or because patients presenting with psychiatric diagnoses were excluded from QOL assessment. Given the importance of psychiatric conditions in primary care practice with a prevalence of more than 20% [66
], this limitation is simply unacceptable.
QOL tends to decrease with age [67
], whereas the number of diagnoses increases with age. Thus, it is appropriate to consider age as a potential confounding variable. The effect of age was explored in some of the studies that used QOL as a main outcome measure [37
]. Reference to established norms would have facilitated interpretation of these results.
Only a few of the studies evaluated had explored the effect of gender. Furthermore, their results were contradictory, with gender being more detrimental to the QOL of women in some cases [41
] and men, in others [51
Little has been reported about the effects of other potential confounding variables (e.g., socio-demographic and economic data, health habits, social support, number of drugs prescribed), although these factors are recognized as having an impact on QOL [68
]. A few of the studies that used QOL as a secondary outcome measure considered the influence of socio-economic variables; however, their results were ambiguous, showing an impact in only about half of the studies. Some studies also demonstrated that, although socio-economic variables and health habits were significant predictors of QOL, the number of comorbidities was the strongest independent predictor of QOL [41
]. Only one study took into account social support, and this study revealed a relationship with the mental dimension of QOL [58
]. Only one study took into account the number of drugs prescribed and found an impact on the physical domain of QOL [49
]. This study looked specifically at comorbidities associated with arterial hypertension and their impact on QOL. Finally, other potential confounding variables such as marital status and living arrangements were considered in some studies, with demonstration of an impact on QOL in about half the studies.
Many other factors should be explored in this regard. For example, the presence of coexisting acute conditions, the time since the diagnosis of important chronic conditions, and the duration and prognosis of health problems are among factors that may explain some of the variability in QOL or HRQOL.
In light of the findings of this systematic review, further research is needed to clarify the relationship between multimorbidity and QOL. The early work will certainly be conceptual and theoretical. The resultant conceptual clarity would benefit both researchers and practitioners. How do we define and how should we measure multimorbidity are among the first questions to be addressed. More descriptive studies, which take into account the influence of multiple potential confounders, can then be conducted. Multivariate analyses will help control for the effects of these confounding variables. The effects of age and gender also need to be further explored, with reference to established norms. Although there is still a need for cross-sectional studies, longitudinal studies are also needed to identify changes in the relationship between multimorbidity and QOL over time.
The main limitation of a systematic review is its inability to include all of the relevant literature. We realize that some articles may have been missed during the search stage. However, our review of a huge number of abstracts generated by different strategies improved the sensitivity of the search. Obviously, the absence of a keyword for multimorbidity is a limitation. However, we found that in the majority of cases in which the term "multimorbidity" was used to search, the term "comorbidity" also appeared in the list of keywords. Adding the term "chronic disease" also helped to circumvent the problem. Restricting the search to articles published in French or English is another limitation.