Comorbidity - Synthesis


A total of 14 systematic reviews were identified in the synthesis of evidence for comorbidity, frailty and prognostics. Two were specific to older adults and palliative care in an aged care context [1-3], whereas six were only pertinent to older adults some of which included an aged care setting [4-10] but not necessarily a palliative focus. Three did not limit to older adult cohorts or an aged care setting but were pertinent to an end-of-life context. [11-14]

Quality Statement

The included papers were of acceptable to high quality [2,3,5-9,13,14], although four studies scored poorly [1,4,11,12] due to the lack of reporting on methodology and quality of included studies. These papers were still included in this review due to their relevancy to the topic.

Evidence Synthesis 

Almost two thirds of older adults (over 80yrs) have three or more chronic diseases or comorbidities. The term multimorbidity is often used to describe when 2 or more occur together in one person. [6] The presentation and severity of symptoms will be heterogeneous, but produce cumulative effects for each individual. [6,7,10] Comorbidity and particularly multimorbidity are associated with poorer quality of life, increased use of health services and hospitalisation, and polypharmacy. [6,7] While evidence-based guidelines exist for the management of a single disease, few address comorbidity particularly in a palliative care context. [6,13] There is a low inclusion rate of older adults in comorbidity randomised clinical trials and therefore reinforces the difficulty in creating appropriate clinical protocols for their management. [7]

Clinicians may need to pursue more flexible approaches to care of older adults with comorbidities in a palliative care context. [10] Some proposed adjustments in line with person-focused care aim more at fulfilment and quality of life rather an improvement in health status. [13] A number of domains have been raised as pertinent to older adults with comorbidities, although not specific to palliative care, such topics have relevancy to this context. [10,13]

Key Themes

  • Individual preferences for care goals – what to focus on in management of comorbidities
  • Prognosis - Benefits and harms of treatment plan
  • Treatment complexity and optimising therapies

Care goals and prognostication

Prognostic factors are often used to determine the start of palliative care and subsequent discussions for end-of-life planning. A diagnosis such as cancer often causes a clear and sudden deterioration in a person’s physical health in the last weeks of life. In organ system failure (e.g. chronic heart failure), the person’s health deteriorates more gently with symptom flare-ups. In advanced dementia or frailty, the person’s health declines gently over a long period. Frailty with ageing and diagnosis of one or more comorbidities can accelerate the expected decline in health and prognostication can become difficult. Importantly, frailty may unintentionally marginalise the person’s views and wishes in the decision-making process. [3]

Health status may also be used at an organisational level to qualify older adults for access to hospice services or entry to residential care. In the systematic review by Brown et al. [1] looking at prognosticators for advanced dementia, only seven studies were found that identified prognostic outcomes. Overall there was no consensus on which is the best scale to use although limitations of the FAST scale were highlighted; it does not take into account the impact on disease progression as a result of comorbidities despite literature suggesting this being an important prognostic factor. 
The most common outcomes were related to nutrition, eating habits and dementia severity scales with reference to comorbidities. Other less well documented outcomes were ambulation and unstable medical conditions. [1] With regard to nutrition outcomes, the review by Veronese et al. [9] examined the relationship of BMI with mortality in older adults in residential aged care. In agreement with studies in younger adults, overweight status seems to offer mild protection whereas being underweight significantly increases risk of mortality. However the authors do conclude with a number of study limitations and suggest that while overweight and obesity may be protective in older adults, the impact of high BMI on comorbidities and quality of life should not be ignored [9]. More research on weight trajectories and comorbidities in a longitudinal study design is desirable in this context.

In a systematic review by Salpeter et al., [12] the authors conclude that common end-of-life clinical presentations in advanced non-cancer illnesses and consistent with an approximate 6-month prognosis include poor functional performance, advanced age, malnutrition, comorbid illness, organ dysfunction and hospitalisation for acute deterioration in health. Despite the therapeutic resistance of chronic illnesses in their late stage, clinical practice still appears to be biased towards treatment and gives rise to older adults receiving invasive procedures and polypharmacy despite it not prolonging survival. [12]

Although prognosis has traditionally focused on remaining life expectancy; functional disability and quality of life represent additional outcomes of particular relevance for older persons with multiple comorbidity (2 or more chronic medical conditions) or ‘multimorbidity’. [6,10] Each person’s prognosis informs, but does not dictate, clinical management decisions within the context of their preferences. It is estimated that ~40% of deaths are associated with multiple comorbidities and a degree of cognitive impairment but no overriding diagnosis which can make prognostication particularly difficult. [11]

The Australian Commission on Safety and Quality in Health Care (ACSQHC) is currently developing quality and safety indicators for end-of-life care in acute hospitals. In a rapid review to identify existing indicators and their validity, a diverse range of information was found. [14] Most of the indicators (approx. 80%) identified in the review relate to either to the provision of expert care or communication and shared decision-making; very few (<10%) focused on respectful care or trust and confidence in clinicians. The sets of indicators identified in the review rarely match the elements of end-of-life care in hospital settings that are valued by patients and their families. None of the sets of indicators mention futile treatments.

Treatment complexity

A discussion about prognosis can serve as a springboard for difficult conversations with older people with comorbidity, and may thus facilitate shared decision-making and advance care planning. [10] Evaluating and discussing prognosis can often inform several facets of care simultaneously, including elucidation of patient preferences, mitigation of treatment complexity, and prioritisation of therapies most likely to benefit an individual. [10]
Older adults are more prone to adverse drug reactions but despite this, polypharmacy (>5 medications) in the management of multimorbidity are common. [4,6] By adhering to clinical practice guidelines there may be several undesirable side effects in the interactions between a medication and a disease; medications for different diseases and medications and food. Undesirable outcomes can include falls, delirium and cognitive impairment, although these are less well studied than effects on functional outcomes. [4] Therefore some medications may be therapeutically omitted where burden outweighs benefits. [10,13]

In the review by Tjia et al. [5] a review of interventions where medications were ceased in frail older adults found of the 36 studies included only three were in a palliative care or hospice context and only one of these used limited life expectancy as a factor in prescribing. Clearly there is a lack of evidence in this context, but in general findings are that prescriptions can be reduced which has associated improvements with process outcomes such as overuse and inappropriate use. However, the evidence on which this review was based is weak and there continues to be no explicit list of medications that can be ceased for frail older adults and any changes to medication regimes should be individualised.

Conversely, a review by Drageset et al. [2] found that in an aged care context, older adults were less frequently prescribed pain medication for symptoms from a cancer diagnosis than in a home or acute care setting. For many older adults with cancer, admission to an aged care facility occurs at end-of-life. Symptoms of pain as well as a number of other acute and chronic quality of life reducing symptoms may be present. Timely assessment and management of these is important. It is recognised that additional comorbidity of dementia further reduces prescribing and treatment of cancer related symptoms in an aged care setting. The authors call for more research and better guidance for pain assessment in these individuals, particularly in avoiding unnecessary prescribing of behaviour medication where changes may have been precipitated by pain and not cognitive decline. [2] The review by Stewart et al. [6] concludes that there are many challenges in implementing appropriate prescribing in this population and the approach should be person centred, clinically robust, multidisciplinary and designed to fit the healthcare system in which it is delivered. 

Similarly, screening procedures such as prostate-specific antigen testing, mammography, and colonoscopy may not be beneficial or may be even harmful if the time horizon to benefit is longer than remaining life expectancy, especially because the harms and burdens associated with many of these tests increase with age and comorbidity. [10] Finally, the decision to not resuscitate 'DNR’ has implications for older adults with multimorbidity and already poor functional status. [8] In the systematic review by de Decker et al. [8] the authors conclude that DNR orders are already more likely to be in place for older adults with multimorbidity, in particular for people with cognitive impairment particularly where decisions have been influenced by prognosis and quality of life. 

In summary, all clinicians, including primary care providers (physicians, physician assistants, and nurse practitioners), pharmacists, geriatricians, specialists, and other clinicians who take care of older adults with multimorbidity often find themselves challenged on many levels. Of particular concern are complexities involved in clinical management decisions; inadequacy of good evidence for making informed, shared decisions; and time constraints and reimbursement structures that hinder the provision of efficient quality care. [10] This is further compounded in a residential aged care context where specialist staff in palliative care may not have regular contact with the person and regular carers and physicians have not been adequately upskilled. Currently there is insufficient evidence or guidelines to facilitate prognostication, appropriate polypharmacy and symptom management for older adults with multimorbidity.

Evidence gaps

  • Prognostication in older adults with multimorbidity remains poorly understood. Measures need to be developed, refined, externally validated, and tested for feasibility and effect on clinical outcomes for older people receiving palliative care.
  • Does frailty attenuate the views and wishes of an older person at end-of-life? Are frail older people marginalised during the decision-making process? Research answering these questions will address practice and policy of patient agency in end-of-life decision-making.
  • Further investigation is needed to help our understanding of clinician-related factors, such as:
    • how clinicians use prognosis to inform treatment plans,
    • and what methods are used to communicate this information to the individuals concerned and their families. 
  • More research is also needed to identify the 'best' approaches for incorporating prognosis into clinical decision-making for older adults with multimorbidity.

Page updated 24 May 2017

  • References

  1. Brown MA, Sampson EL, Jones L, Barron AM. Prognostic indicators of 6-month mortality in elderly people with advanced dementia: A systematic review. Palliat Med. 2013 May;27(5):389-400.
  2. Drageset J, Corbett A, Selbaek G, Husebo BS. Cancer-related pain and symptoms among nursing home residents: a systematic review. J Pain Symptom Manage. 2014 Oct;48(4):699-710.e1.
  3. Birchley G, Jones K, Huxtable R, Dixon J, Kitzinger J, Clare L. Dying well with reduced agency: a scoping review and thematic synthesis of the decision-making process in dementia, traumatic brain injury and frailty. BMC Med Ethics. 2016 Jul 27;17(1):46.
  4. van der Cammen TJ, Rajkumar C, Onder G, Sterke CS, Petrovic M. Drug cessation in complex older adults: time for action. Age Ageing. 2014 Jan;43(1):20-5.
  5. Tjia J, Velten SJ, Parsons C, Valluri S, Briesacher BA. Studies to reduce unnecessary medication use in frail older adults: a systematic review. Drugs Aging. 2013 May;30(5):285-307.
  6. Stewart D, Mair A, Wilson M, Kardas P, Lewek P, Alonso A, et al. Guidance to manage inappropriate polypharmacy in older people: systematic review and future developments. Expert Opin Drug Saf. 2017 Feb;16(2):203-213.
  7. Nunes BP, Flores TR, Mielke GI, Thume E, Facchini LA. Multimorbidity and mortality in older adults: A systematic review and meta-analysis. Arch Gerontol Geriatr. 2016 Nov-Dec;67:130-8.
  8. de Decker L, Annweiler C, Launay C, Fantino B, Beauchet O. Do not resuscitate orders and aging: impact of multimorbidity on the decision-making process. J Nutr Health Aging. 2014 Mar;18(3):330-5.
  9. Veronese N, Cereda E, Solmi M, Fowler SA, Manzato E, Maggi S, et al. Inverse relationship between body mass index and mortality in older nursing home residents: A meta-analysis of 19,538 elderly subjects. Obes Rev. 2015 Nov;16(11):1001-15.
  10. American Geriatrics Society Expert Panel on the Care of Older Adults with M. Guiding Principles for the Care of Older Adults with Multimorbidity: An Approach for Clinicians. J Am Geriat Soc. 2012 Oct;60(10):E1-E25.
  11. Sharp T, Moran E, Kuhn I, Barclay S. Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis. Br J Gen Pract. 2013 Oct;63(615):e657-68.
  12. Salpeter SR, Luo EJ, Malter DS, Stuart B. Systematic review of noncancer presentations with a median survival of 6 months or less. Am J Med. 2012 May;125(5):512.e1-6.
  13. Mangin D, Stephen G, Bismah V, Risdon C. Making patient values visible in healthcare: a systematic review of tools to assess patient treatment priorities and preferences in the context of multimorbidity. BMJ Open. 2016 Jun 10;6(6):e010903.
  14. Masso M, Samsa P, P G. Rapid review of the literature to inform the development of quality and safety indicators for end-of-life care in acute hospitals (1.1MB pdf). Sydney: ACSHQ, 2016 June.