- Email: [email protected]
Precision medicine to precision care: managing multimorbidity
Comment
about the breadth and duration of protection, and the cost-effectiveness of programmes. Evidence of high vaccine effectiveness, along with high vaccine uptake, should be reassuring to health authorities who are considering whether to introduce vaccine programmes against MenB disease. In addition, cost-effectiveness analyses played a central part in the decision to introduce 4CMenB in the UK.12 To inform vaccination policies in other settings, additional epidemiological and cost-effectiveness studies are now needed to answer important remaining questions, including how differences in the age distribution of MenB cases, variation in the relative frequencies of disease-causing MenB strains, the potential impact of MenB vaccines on carriage among teenagers, and variation in the costs of vaccination programmes could affect the impact of MenB vaccines. If the reductions in MenB disease that Parikh and colleagues observed among UK infants are sustained over time and replicated in other settings, then MenB vaccines could have a vital role in reducing the threat of meningococcal disease.
interventions at the University of Bristol in partnership with Public Health England (PHE). HC has collaborated with PHE when developing mathematical and economic models predicting the impact of 4CMenB in the UK and has co-authored papers with PHE colleagues, including Article authors Shamez Ladhani, Helen Campbell, Ray Borrow, and Mary Ramsay, on preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using Bexsero, but she had no involvement in the present Article. HC has received honoraria from Sanofi Pasteur, paid to her employer, and consultancy fees from IMS Health and AstraZeneca. The views expressed are those of the author(s) and not necessarily those of the NIH, NHS, the NIHR, the Department of Health, or Public Health England. 1 2 3 4
5
6 7
8
9
*Nicole E Basta, Hannah Christensen University of Minnesota, School of Public Health, Minneapolis, MN 55454, USA (NEB); and University of Bristol, School of Social and Community Medicine, Bristol, England, UK (HC) [email protected] NEB is funded by the National Institutes of Health Early Independence Award from the Office of the Director (1DP5OD009162). NEB has collaborated with Ray Borrow and co-authored studies of meningococcal A and B vaccines using data from the USA and Africa. HC is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in evaluation of
10
11
12
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. Vaccine 2009; 27: B51–63. Khatami A, Pollard AJ. The epidemiology of meningococcal disease and the impact of vaccines. Expert Rev Vaccines 2010; 9: 285–98. Campbell H, Borrow R, Salisbury D, Miller E. Meningococcal C conjugate vaccine: the experience in England and Wales. Vaccine 2009; 27: B20–29. Daugla DM, Gami JP, Gamougam K, et al. Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study. Lancet 2014; 383: 40–47. Esposito S, Principi N. Vaccine profile of 4CMenB: a four-component Neisseria meningitidis serogroup B vaccine. Expert Rev Vaccines 2014; 13: 193–202. Brendish NJ, Read RC. Neisseria meningitidis serogroup B bivalent factor H binding protein vaccine. Expert Rev Vaccines 2015; 14: 493–503. Ladhani SN, Campbell H, Parikh SR, Saliba V, Borrow R, Ramsay M. The introduction of the meningococcal B (MenB) vaccine (Bexsero®) into the national infant immunisation programme—new challenges for public health. J Infect 2015; 71: 611–14. Ladhani SN, Ramsay M, Borrow R, Riordan A, Watson JM, Pollard AJ. Enter B and W: two new meningococcal vaccine programmes launched. Arch Dis Child 2016; 101: 91–95. Parikh SR, Andrews NJ, Beebeejaun K, et al. Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study. Lancet 2016; published online Oct 27. http://dx.doi.org/10.1016/S0140-6736(16)31921-3. Santolaya ME, O’Ryan ML, Valenzuela MT, et al. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet 2012; 379: 617–24. Basta NE, Mahmoud AA, Wolfson J, et al. Immunogenicity of a meningococcal B vaccine during a university outbreak. N Engl J Med 2016; 375: 220–28. Christensen H, Trotter CL, Hickman M, Edmunds WJ. Re-evaluating cost effectiveness of universal meningitis vaccination (Bexsero) in England: modelling study. BMJ 2014; 349: g5725.
Precision medicine to precision care: managing multimorbidity The gap between traditional disease-focused medicine and patients’ needs is growing as the burden of multimorbidity increases.1 This mismatch, which stems from both successes (eg, increasing life expectancy and advances in biomedicine) and failures (eg, underinvestment in prevention and focus on managing discrete disease rather than what matters to each patient), results in fragmented care, suboptimal health outcomes, and avoidable harms for patients with multiple chronic conditions. Although multimorbidity is common among older adults (aged ≥65 years), it is also common in younger populations. www.thelancet.com Vol 388 December 3, 2016
In the USA in 2010, over 60% of adults aged 65 years or more had two or more chronic conditions as did a third of adults aged 45–64 years.2 Socioeconomically disadvantaged individuals have a higher burden of multimorbidity, and they develop multiple chronic conditions 10–15 years earlier than do those who are more socioeconomically advantaged.3 People with multimorbidity are common users of health care, generate high costs, and are at increased risk for adverse events. Most of these individuals are cared for by practitioners with inadequate expertise in geriatrics or multimorbidity. 2721
Burger/Phanie/Science Photo Library
Comment
Clinical practice guidelines, based on evidence from clinical trials that often exclude patients with multiple chronic conditions, rarely provide the guidance necessary to optimise their care. Unconsidered application of multiple single disease guidelines can lead to polypharmacy with drug–drug or drug–disease interactions, contradictory recommendations, high treatment burden, inattention to social and personal context, and failure to align care with personal goals and preferences.4,5 Efforts to improve healthcare quality using performance measures based on single disease guidelines can yield unclear benefit and unintended harms for patients with multiple chronic conditions. Guidance for management of multimorbidity in clinical practice is insufficient. The new National Institute for Health and Care Excellence (NICE) guideline Multimorbidity: Clinical Assessment and Management,6 released on Sept 21, 2016, along with supporting evidence from systematic reviews and resources for practitioners to facilitate implementation, helps to fill this gap. The guideline builds on well established geriatric principles7 and principles of primary care practice articulated in the Ariadne principles.8 The patient-centred approach of the NICE guideline is a welcome addition to existing guidelines for common chronic conditions that address clinical management in the context of comorbidity.9 The NICE guideline6 joins a growing number of resources developed to help clinicians to optimise care for patients with multiple chronic 2722
conditions. The National Guideline Clearinghouse10 now tags guidelines, allowing users to identify those that address multiple chronic conditions, and facilitates searching by combinations of conditions. The American Geriatrics Society (AGS) produced a toolkit to support the management of multimorbidity in older adults. The AGS diabetes guideline11 recommends different goals for glycaemic control depending on the patient’s health status. Additionally, the US Agency for Healthcare Research and Quality has developed the Integration Playbook12 to guide practices in integrating behavioural health into primary care and other ambulatory care settings. Provision of effective care for people with multimorbidity requires dynamic individualised care plans. Core elements of these plans should include optimising quality of life, eliciting preferences and goals, weighing risks and benefits of implementing recommendations from single disease guidelines, addressing trade-offs, setting priorities, stopping potentially harmful or unnecessary medications and starting beneficial medications while simplifying regimens, integrating care, and minimising treatment burden. Similar elements have been included in a framework for priority-directed decision making and care of patients with multimorbidity.13 The NICE guideline6 provides a framework based on increasing complexity of needed care, and guidance on how to identify patients who would benefit. This guidance is important because although some individuals with a single complex condition would benefit from application of these principles, not everyone with two or more long-term conditions (eg, mild hypertension and osteoarthritis) requires this intensive approach. The NICE guideline recommends that an explicit decision be made as to how and when single disease guidelines should be applied. Patients with multiple chronic conditions might be best served if clinicians actively rule in the use of disease-specific guidelines. Much attention has been paid to the promise of precision medicine, a term usually used to describe the approach for disease treatment and prevention that takes into account individual variability in their genes, environment, and lifestyle. In the context of multimorbidity, however, precision medicine entails carefully considering the applicability of each recommendation to an individual’s profile www.thelancet.com Vol 388 December 3, 2016
Comment
of conditions, health and functional status, goals, and preferences. Transformation of health-care delivery to optimise care for people with multimorbidity will require changes in clinical practice, medical education, performance and quality measurement, research, and policy. The availability of personalised recommendations for care will make clinical decision making and care planning even more complex. Furthermore, precision measurement is needed to develop quality indicators that effectively assess people-centred care. In the UK, exception reports allow primary care physicians to exclude patients from quality indicators because of clinical judgment. However, this exclusion is not allowed in other jurisdictions. Furthermore, this exception reporting ignores the need to measure and improve quality of care among patients with multimorbidity. The development of quality indicators aligned with patient goals is needed along with measures of care integration and treatment burden. Use of patient-reported outcome measures can help focus care on outcomes that are meaningful to patients. Other measures that assess the extent to which patients’ goals are met, such as goal attainment scaling, might prove to be a viable option. Systematic reviews done by NICE found insufficient evidence to make recommendations in key domains, and identified four priority areas for research, including the effectiveness of alternative approaches to organise care for people with multimorbidity. Models of care should be tailored to available resources, workforce, and the community served. Previous work on primary care medical homes and their surrounding medical neighbourhood can inform this research. Health information technology can provide tools to coordinate care and share care plans developed in partnership with patients. Clinical decision support at the point of care might facilitate shared decision making, assuming that decision making accounts for goals and preferences across conditions not simply within a single condition. Improvement of data infrastructure in learning health systems can support clinical and health services research on the most effective ways to optimise care for people with multimorbidity. Multimorbidity is the most common condition managed in practice. Health-care delivery must be
www.thelancet.com Vol 388 December 3, 2016
transformed to provide precision care to people with multimorbidity. Accomplishing this transition will require a change in practice, research, and policy from disease-specific to patient-centred models of care delivery. *Arlene S Bierman, Mary E Tinetti Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, Rockville, MD 20857, USA (ASB); and Department of Medicine, Yale School of Medicine, and Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA (MET) [email protected] We declare no competing interests. The views in this manuscript represent the authors and not necessarily the policy or views of the Agency for Health Care Research and Quality or the US Department of Health and Human Services. 1 2
3
4
5
6
7
8
9
10
11
12
13
Prince MJ, Wu F, Guo Y, et al. The burden of disease in older people and implications for health policy and practice. Lancet 2015; 385: 549–62. Ward BW, Schiller JS. Prevalence of multiple chronic conditions among US adults: estimates from the National Health Interview Survey, 2010. Prev Chronic Dis 2013; 10: e65. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 2012; 380: 37–43. Wyatt KD, Stuart LM, Brito JP, et al. Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review. Med Care 2014; 52 (suppl 3): S92–100. Tinetti ME, Bogardus ST Jr, Agostini JV. Potential pitfalls of disease-specific guidelines for patients with multiple conditions. N Engl J Med 2004; 351: 2870–74. NICE. Multimorbidity: clinical assessment and management. 2016. http://www.nice.org.uk/guidance/NG56/documents/html-content (accessed Nov 13, 2016). American Geriatrics Society. Guiding principles for the care of older adults with multimorbidity: an approach for clinicians: American Geriatrics Society Expert Panel on the care of older adults with multimorbidity. J Am Geriatr Soc 2012; 60: e1–25. Muth C, van den Akker M, Blom JW, et al. The Ariadne principles: how to handle multimorbidity in primary care consultations. BMC Med 2014; 12: 223. Arnett DK, Goodman RA, Halperin JL, Anderson JL, Parekh AK, Zoghbi WA. AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardiovascular disease and comorbid conditions: from the American Heart Association, American College of Cardiology, and US Department of Health and Human Services. J Am Coll Cardiol 2014; 64: 1851–56. National Guideline Clearinghouse. About multiple chronic condition (MCC) guidelines. 2016. https://www.guideline.gov/help-and-about/summaries/ about-multiple-chronic-condition-mcc-guidelines (accessed Nov 13, 2016). Moreno G, Mangione CM, Kimbro L, Vaisberg E, for the American Geriatrics Society Expert Panel on Care of Older Adults with Diabetes Mellitus. Guidelines abstracted from the American Geriatrics Society guidelines for improving the care of older adults with diabetes mellitus: 2013 update. J Am Geriatr Soc 2013; 61: 2020–26. Korsen N, Blount A, Peek CJ, et al. Integration Playbook: Agency for Healthcare Research and Quality, Academy for Integrating Behavioral Health and Primary Care. 2016. http://integrationacademy.ahrq.gov/ playbook/about-playbook (accessed Nov 13, 2016). Tinetti ME, Esterson J, Ferris R, Posner P, Blaum CS. Patient priority-directed decision making and care for older adults with multiple chronic conditions. Clin Geriatr Med 2016; 32: 261–75.
2723
about the breadth and duration of protection, and the cost-effectiveness of programmes. Evidence of high vaccine effectiveness, along with high vaccine uptake, should be reassuring to health authorities who are considering whether to introduce vaccine programmes against MenB disease. In addition, cost-effectiveness analyses played a central part in the decision to introduce 4CMenB in the UK.12 To inform vaccination policies in other settings, additional epidemiological and cost-effectiveness studies are now needed to answer important remaining questions, including how differences in the age distribution of MenB cases, variation in the relative frequencies of disease-causing MenB strains, the potential impact of MenB vaccines on carriage among teenagers, and variation in the costs of vaccination programmes could affect the impact of MenB vaccines. If the reductions in MenB disease that Parikh and colleagues observed among UK infants are sustained over time and replicated in other settings, then MenB vaccines could have a vital role in reducing the threat of meningococcal disease.
interventions at the University of Bristol in partnership with Public Health England (PHE). HC has collaborated with PHE when developing mathematical and economic models predicting the impact of 4CMenB in the UK and has co-authored papers with PHE colleagues, including Article authors Shamez Ladhani, Helen Campbell, Ray Borrow, and Mary Ramsay, on preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using Bexsero, but she had no involvement in the present Article. HC has received honoraria from Sanofi Pasteur, paid to her employer, and consultancy fees from IMS Health and AstraZeneca. The views expressed are those of the author(s) and not necessarily those of the NIH, NHS, the NIHR, the Department of Health, or Public Health England. 1 2 3 4
5
6 7
8
9
*Nicole E Basta, Hannah Christensen University of Minnesota, School of Public Health, Minneapolis, MN 55454, USA (NEB); and University of Bristol, School of Social and Community Medicine, Bristol, England, UK (HC) [email protected] NEB is funded by the National Institutes of Health Early Independence Award from the Office of the Director (1DP5OD009162). NEB has collaborated with Ray Borrow and co-authored studies of meningococcal A and B vaccines using data from the USA and Africa. HC is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in evaluation of
10
11
12
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. Vaccine 2009; 27: B51–63. Khatami A, Pollard AJ. The epidemiology of meningococcal disease and the impact of vaccines. Expert Rev Vaccines 2010; 9: 285–98. Campbell H, Borrow R, Salisbury D, Miller E. Meningococcal C conjugate vaccine: the experience in England and Wales. Vaccine 2009; 27: B20–29. Daugla DM, Gami JP, Gamougam K, et al. Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study. Lancet 2014; 383: 40–47. Esposito S, Principi N. Vaccine profile of 4CMenB: a four-component Neisseria meningitidis serogroup B vaccine. Expert Rev Vaccines 2014; 13: 193–202. Brendish NJ, Read RC. Neisseria meningitidis serogroup B bivalent factor H binding protein vaccine. Expert Rev Vaccines 2015; 14: 493–503. Ladhani SN, Campbell H, Parikh SR, Saliba V, Borrow R, Ramsay M. The introduction of the meningococcal B (MenB) vaccine (Bexsero®) into the national infant immunisation programme—new challenges for public health. J Infect 2015; 71: 611–14. Ladhani SN, Ramsay M, Borrow R, Riordan A, Watson JM, Pollard AJ. Enter B and W: two new meningococcal vaccine programmes launched. Arch Dis Child 2016; 101: 91–95. Parikh SR, Andrews NJ, Beebeejaun K, et al. Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study. Lancet 2016; published online Oct 27. http://dx.doi.org/10.1016/S0140-6736(16)31921-3. Santolaya ME, O’Ryan ML, Valenzuela MT, et al. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet 2012; 379: 617–24. Basta NE, Mahmoud AA, Wolfson J, et al. Immunogenicity of a meningococcal B vaccine during a university outbreak. N Engl J Med 2016; 375: 220–28. Christensen H, Trotter CL, Hickman M, Edmunds WJ. Re-evaluating cost effectiveness of universal meningitis vaccination (Bexsero) in England: modelling study. BMJ 2014; 349: g5725.
Precision medicine to precision care: managing multimorbidity The gap between traditional disease-focused medicine and patients’ needs is growing as the burden of multimorbidity increases.1 This mismatch, which stems from both successes (eg, increasing life expectancy and advances in biomedicine) and failures (eg, underinvestment in prevention and focus on managing discrete disease rather than what matters to each patient), results in fragmented care, suboptimal health outcomes, and avoidable harms for patients with multiple chronic conditions. Although multimorbidity is common among older adults (aged ≥65 years), it is also common in younger populations. www.thelancet.com Vol 388 December 3, 2016
In the USA in 2010, over 60% of adults aged 65 years or more had two or more chronic conditions as did a third of adults aged 45–64 years.2 Socioeconomically disadvantaged individuals have a higher burden of multimorbidity, and they develop multiple chronic conditions 10–15 years earlier than do those who are more socioeconomically advantaged.3 People with multimorbidity are common users of health care, generate high costs, and are at increased risk for adverse events. Most of these individuals are cared for by practitioners with inadequate expertise in geriatrics or multimorbidity. 2721
Burger/Phanie/Science Photo Library
Comment
Clinical practice guidelines, based on evidence from clinical trials that often exclude patients with multiple chronic conditions, rarely provide the guidance necessary to optimise their care. Unconsidered application of multiple single disease guidelines can lead to polypharmacy with drug–drug or drug–disease interactions, contradictory recommendations, high treatment burden, inattention to social and personal context, and failure to align care with personal goals and preferences.4,5 Efforts to improve healthcare quality using performance measures based on single disease guidelines can yield unclear benefit and unintended harms for patients with multiple chronic conditions. Guidance for management of multimorbidity in clinical practice is insufficient. The new National Institute for Health and Care Excellence (NICE) guideline Multimorbidity: Clinical Assessment and Management,6 released on Sept 21, 2016, along with supporting evidence from systematic reviews and resources for practitioners to facilitate implementation, helps to fill this gap. The guideline builds on well established geriatric principles7 and principles of primary care practice articulated in the Ariadne principles.8 The patient-centred approach of the NICE guideline is a welcome addition to existing guidelines for common chronic conditions that address clinical management in the context of comorbidity.9 The NICE guideline6 joins a growing number of resources developed to help clinicians to optimise care for patients with multiple chronic 2722
conditions. The National Guideline Clearinghouse10 now tags guidelines, allowing users to identify those that address multiple chronic conditions, and facilitates searching by combinations of conditions. The American Geriatrics Society (AGS) produced a toolkit to support the management of multimorbidity in older adults. The AGS diabetes guideline11 recommends different goals for glycaemic control depending on the patient’s health status. Additionally, the US Agency for Healthcare Research and Quality has developed the Integration Playbook12 to guide practices in integrating behavioural health into primary care and other ambulatory care settings. Provision of effective care for people with multimorbidity requires dynamic individualised care plans. Core elements of these plans should include optimising quality of life, eliciting preferences and goals, weighing risks and benefits of implementing recommendations from single disease guidelines, addressing trade-offs, setting priorities, stopping potentially harmful or unnecessary medications and starting beneficial medications while simplifying regimens, integrating care, and minimising treatment burden. Similar elements have been included in a framework for priority-directed decision making and care of patients with multimorbidity.13 The NICE guideline6 provides a framework based on increasing complexity of needed care, and guidance on how to identify patients who would benefit. This guidance is important because although some individuals with a single complex condition would benefit from application of these principles, not everyone with two or more long-term conditions (eg, mild hypertension and osteoarthritis) requires this intensive approach. The NICE guideline recommends that an explicit decision be made as to how and when single disease guidelines should be applied. Patients with multiple chronic conditions might be best served if clinicians actively rule in the use of disease-specific guidelines. Much attention has been paid to the promise of precision medicine, a term usually used to describe the approach for disease treatment and prevention that takes into account individual variability in their genes, environment, and lifestyle. In the context of multimorbidity, however, precision medicine entails carefully considering the applicability of each recommendation to an individual’s profile www.thelancet.com Vol 388 December 3, 2016
Comment
of conditions, health and functional status, goals, and preferences. Transformation of health-care delivery to optimise care for people with multimorbidity will require changes in clinical practice, medical education, performance and quality measurement, research, and policy. The availability of personalised recommendations for care will make clinical decision making and care planning even more complex. Furthermore, precision measurement is needed to develop quality indicators that effectively assess people-centred care. In the UK, exception reports allow primary care physicians to exclude patients from quality indicators because of clinical judgment. However, this exclusion is not allowed in other jurisdictions. Furthermore, this exception reporting ignores the need to measure and improve quality of care among patients with multimorbidity. The development of quality indicators aligned with patient goals is needed along with measures of care integration and treatment burden. Use of patient-reported outcome measures can help focus care on outcomes that are meaningful to patients. Other measures that assess the extent to which patients’ goals are met, such as goal attainment scaling, might prove to be a viable option. Systematic reviews done by NICE found insufficient evidence to make recommendations in key domains, and identified four priority areas for research, including the effectiveness of alternative approaches to organise care for people with multimorbidity. Models of care should be tailored to available resources, workforce, and the community served. Previous work on primary care medical homes and their surrounding medical neighbourhood can inform this research. Health information technology can provide tools to coordinate care and share care plans developed in partnership with patients. Clinical decision support at the point of care might facilitate shared decision making, assuming that decision making accounts for goals and preferences across conditions not simply within a single condition. Improvement of data infrastructure in learning health systems can support clinical and health services research on the most effective ways to optimise care for people with multimorbidity. Multimorbidity is the most common condition managed in practice. Health-care delivery must be
www.thelancet.com Vol 388 December 3, 2016
transformed to provide precision care to people with multimorbidity. Accomplishing this transition will require a change in practice, research, and policy from disease-specific to patient-centred models of care delivery. *Arlene S Bierman, Mary E Tinetti Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, Rockville, MD 20857, USA (ASB); and Department of Medicine, Yale School of Medicine, and Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA (MET) [email protected] We declare no competing interests. The views in this manuscript represent the authors and not necessarily the policy or views of the Agency for Health Care Research and Quality or the US Department of Health and Human Services. 1 2
3
4
5
6
7
8
9
10
11
12
13
Prince MJ, Wu F, Guo Y, et al. The burden of disease in older people and implications for health policy and practice. Lancet 2015; 385: 549–62. Ward BW, Schiller JS. Prevalence of multiple chronic conditions among US adults: estimates from the National Health Interview Survey, 2010. Prev Chronic Dis 2013; 10: e65. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 2012; 380: 37–43. Wyatt KD, Stuart LM, Brito JP, et al. Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review. Med Care 2014; 52 (suppl 3): S92–100. Tinetti ME, Bogardus ST Jr, Agostini JV. Potential pitfalls of disease-specific guidelines for patients with multiple conditions. N Engl J Med 2004; 351: 2870–74. NICE. Multimorbidity: clinical assessment and management. 2016. http://www.nice.org.uk/guidance/NG56/documents/html-content (accessed Nov 13, 2016). American Geriatrics Society. Guiding principles for the care of older adults with multimorbidity: an approach for clinicians: American Geriatrics Society Expert Panel on the care of older adults with multimorbidity. J Am Geriatr Soc 2012; 60: e1–25. Muth C, van den Akker M, Blom JW, et al. The Ariadne principles: how to handle multimorbidity in primary care consultations. BMC Med 2014; 12: 223. Arnett DK, Goodman RA, Halperin JL, Anderson JL, Parekh AK, Zoghbi WA. AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardiovascular disease and comorbid conditions: from the American Heart Association, American College of Cardiology, and US Department of Health and Human Services. J Am Coll Cardiol 2014; 64: 1851–56. National Guideline Clearinghouse. About multiple chronic condition (MCC) guidelines. 2016. https://www.guideline.gov/help-and-about/summaries/ about-multiple-chronic-condition-mcc-guidelines (accessed Nov 13, 2016). Moreno G, Mangione CM, Kimbro L, Vaisberg E, for the American Geriatrics Society Expert Panel on Care of Older Adults with Diabetes Mellitus. Guidelines abstracted from the American Geriatrics Society guidelines for improving the care of older adults with diabetes mellitus: 2013 update. J Am Geriatr Soc 2013; 61: 2020–26. Korsen N, Blount A, Peek CJ, et al. Integration Playbook: Agency for Healthcare Research and Quality, Academy for Integrating Behavioral Health and Primary Care. 2016. http://integrationacademy.ahrq.gov/ playbook/about-playbook (accessed Nov 13, 2016). Tinetti ME, Esterson J, Ferris R, Posner P, Blaum CS. Patient priority-directed decision making and care for older adults with multiple chronic conditions. Clin Geriatr Med 2016; 32: 261–75.
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