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General Practice Articles Department of General Practice

1-1-2015

Managing patients with multimorbidity in primary care. Emma Wallace Royal College of Surgeons in Ireland

Chris Salisbury University of Bristol

Bruce Guthrie University of Dundee

Cliona Lewis Royal College of Surgeons in Ireland

Tom Fahey Royal College of Surgeons in Ireland

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This Article is brought to you for free and open access by the Department of General Practice at e-publications@RCSI. It has been accepted for inclusion in General Practice Articles by an authorized administrator of e- publications@RCSI. For more information, please contact [email protected].

Citation Wallace E, Salisbury C, Guthrie B, Lewis C, Fahey T, Smith SM. Managing patients with multimorbidity in primary care. British Medical Journal. 2015;350:h176.

Authors Emma Wallace, Chris Salisbury, Bruce Guthrie, Cliona Lewis, Tom Fahey, and Susan M. Smith

This article is available at e-publications@RCSI: http://epubs.rcsi.ie/gpart/70

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This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

This article is available at e-publications@RCSI: http://epubs.rcsi.ie/gpart/70

Managing patients with multimorbidity in primary care Emma Wallace general practice lecturer 1, Chris Salisbury professor in primary health care 2, Bruce Guthrie professor of primary care medicine 3, Cliona Lewis general practice lecturer 1, Tom Fahey professor of general practice 1, Susan M Smith associate professor of general practice 1

1HRB Centre for Primary Care Research, Royal College of Surgeons in Ireland Medical School, Dublin 2, Ireland; 2Centre for Academic Primary Care, University of Bristol, Bristol, UK; 3Quality, Safety and Informatics Research Group, University of Dundee, Dundee, UK

Multimorbidity, commonly defined as the presence of two or more chronic medical conditions in an individual,1 is associated with decreased quality of life, functional decline, and increased healthcare utilisation, including emergency admissions, particularly with higher numbers of coexisting conditions.2-6 The management of multimorbidity with drugs is often complex, resulting in polypharmacy with its attendant risks.7-9 Patients with multimorbidity have a high treatment burden in terms of understanding and self managing the conditions, attending multiple appointments, and managing complex drug regimens.10 Qualitative research highlights the “endless struggle” patients experience in trying to manage their conditions well.11 Psychological distress is common: in an Australian survey of 7620 patients in primary care, 23% of those with one chronic condition reported depression compared with 40% of those with five or more conditions.12

Multimorbidity presents many challenges, which may at times seem overwhelming. This review provides evidence based practice points that are feasible to implement in general practice and offers guidance for general practitioners in organising care delivery.

How common is it? Recent estimates suggest that one in six patients in the United Kingdom has more than one of the conditions outlined in the Quality and Outcomes Framework, and these patients account for approximately one third of all consultations in general practice.13 A recent, large scale Scottish study reported that approximately 65% of those aged more than 65 years and almost 82% of those aged 85 years or more had two or more chronic conditions.14 Although prevalence increases substantially with age, in absolute terms multimorbidity is more prevalent in those aged 65 years or less and is much more common in socioeconomically deprived areas.14 A recent systematic review included 11 studies relating to patterns of multimorbidity. The most common pair of conditions across studies was osteoarthritis and a cardiometabolic condition, such as hypertension, diabetes, obesity, or ischaemic heart disease.15 This review also attempted to identify meaningful groups of conditions. In four studies that

used factor analysis to identify common factors across combinations of conditions, three were consistent across studies; a cardiometabolic condition factor, a mental health condition factor (most commonly depression or anxiety), and a painful condition factor.15

What is the impact of multimorbidity? Box 1 summarises some commonly encountered problems for patients with multimorbidity. In a recent systematic review, general practitioners identified four areas where they experience difficulties in caring for patients with multimorbidity: disorganisation and fragmentation of care, inadequacy of current disease specific guidelines, challenges in delivering patient centred care, and barriers to shared decision making (box 2).16 General practitioners also highlighted the sense of professional isolation they experience in managing these patients.

What are the challenges of chronic disease management in multimorbidity? Inadequacy of single disease clinical guidelines Managing several chronic conditions with the current single disease focus of clinical guidelines and research is a challenge general practitioners face daily. Guidelines rarely deal with comorbidity, in part because they are designed to be based on evidence from randomised controlled trials and because trials routinely exclude older people and people with multiple chronic conditions.23-25 This leads to a situation where every individual recommendation made by a guideline may be rational and evidence based, but the sum of all recommendations in an individual is not. Consider the application of five UK clinical guidelines for a hypothetical 78 year old woman with previous myocardial infarction, type 2 diabetes, osteoarthritis, chronic obstructive pulmonary disease, and depression.26 She would be prescribed a minimum of 11 drugs, with potentially up to 10 others recommended depending on symptoms and progression of disease, and she would be advised to engage in at least nine

Correspondence to: E Wallace [email protected]

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The bottom line

Multimorbidity is commonly defined as the presence of two or more chronic medical conditions in an individual and it can present several challenges in care particularly with higher numbers of coexisting conditions and related polypharmacy Practices should actively identify patients with complex multimorbidity and adopt a policy of continuity of care for these patients by assigning them a named doctor The adoption of a policy for routine extended consultations should be considered for particularly complex patients or the introduction of occasional “specific extended consultations.” allowing protected time to deal with problems encountered in the management of chronic diseases

Sources and selection criteria

We based this article on the authors’ experience and information from published literature. We carried out searches of PubMed and the Cochrane library using the search terms “co-morbidity” or “comorbidity” or “multimorbid” or “multimorbidity” or “multi-morbidity”. No MeSH term exists for multimorbidity. The searches were supplemented by a review of authors’ personal archives as well as relevant articles from the International Research Community on Multimorbidity archive at the University of Sherbrooke, Quebec, Canada (http://crmcspl-blog. recherche.usherbrooke.ca/?page_id=248).

Box 1: Problems commonly experienced by patients with multimorbidity

Fragmentation and poor coordination of care Results from seeing multiple health professionals in primary and secondary care.16 17

Polypharmacy Attendant risk of adverse drug events, potentially inappropriate prescribing, and problems with drug concordance7 18

Treatment burden Results from the necessity of learning about and adhering to management plans and lifestyle changes suggested for different conditions and engaging with multiple healthcare professionals19

Mental health difficulties Anxiety and depression are more common in patients with multimorbidity and can impact on patients’ ability to manage other long term conditions2 12

Patients living in deprived areas are particularly vulnerable to multimorbidity that includes mental health conditions 20

Those with cognitive impairment are also particularly vulnerable and may have added difficulties in managing their conditions21

Functional difficulties Functional difficulties increase with increasing number of conditions and in people aged more than 75 years5 6

Reduced quality of life Associated with the number of chronic medical conditions6

Increased healthcare utilisation Includes an increased risk of emergency admission to hospital4 22

Box 2: Practice points for dealing with challenges in caring for patients with multimorbidity

Disorganisation and fragmentation of care Identify patients as having complex multimorbidity and adopt a practice policy of continuity of care by assigning them a named doctor

Chronic disease management Some evidence supports focusing on functional optimisation of patients with multimorbidity and on shared risk factors for several conditions, such as blood pressure and smoking cessation In the absence of meaningful clinical guidelines, clinical judgment is especially important in the decision making process

Medicines management Plan regular reviews (at least annually) of drugs (explicit prescribing tools for potentially inappropriate prescribing may be useful in reviewing polypharmacy)

Promoting patient centred care Shared decision making—asking patients at the outset of a consultation “What is bothering you most?” or “What would you like to focus on today?” can help prioritise management to those aspects of care that will have the most impact on patients Self management of multimorbidity—research to date is mixed about the benefit of self management, but it may be an option for patients expressing an interest in group based support

Short consultation times Consider adopting a practice policy of routine extended consultations for particularly complex patients or introducing occasional “specific extended consultations,” allowing protected time to deal with problems encountered in the management of chronic diseases Ensure practice systems are in place to maximise the value of the general practice consultation for both patient and doctor in reaching management decisions—for example, by seeing the practice nurse ahead of an appointment with the doctor Arrange multidisciplinary team involvement, where appropriate

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lifestyle modifications. In addition to any unplanned appointments, she would be expected to annually attend 8-10 routine primary care appointments for her physical conditions and 8-30 psychosocial intervention appointments for depression and advised to attend multiple appointments for smoking cessation support and pulmonary rehabilitation.26

One potential solution is for future developers of guidelines to consider addressing more common clusters of chronic conditions.27 Although this is an important step, guidelines to cover all combinations of conditions are unlikely and so the value of clinical judgment should be recognised and supported.28 At times clinical judgment may mean an acceptance that in certain circumstances pursuing stringent disease specific targets is unlikely to be beneficial and may in fact be harmful. Alternatively it may mean prioritising the treatment of depression, which has been shown to impact the ability of patients to manage their other chronic conditions.29 Policy makers who base performance related payments on disease specific targets need to be aware that such trade-offs based on clinical judgment may represent better patient centred care. Other performance measures that truly capture quality of care for this patient group should be considered.

Targeting function not disease The Cochrane systematic review of community based interventions to improve outcomes for patients with multimorbidity identified only 10 randomised controlled trials.30 Of these, six involved changes to the organisation of care delivery, usually through case management, and the remaining four interventions were predominantly patient oriented, including support for self management. Although results were mixed, interventions directed towards particular risk factors shared across comorbid conditions or generic functional difficulties experienced by patients seem promising. One randomised controlled trial delivered by occupational therapists and physiotherapists targeted functional difficulties of 319 patients aged 70 years or older with multimorbidity and improved health outcomes including a statistically significant reduction in mortality two years post-intervention. This highlights the potential importance of a multidisciplinary approach in management and a focus on generic outcomes relevant across conditions.31

Medicines management A recent study of 180 815 adults in primary care reported that approximately 20% of patients with two conditions were prescribed four to nine drugs and 1% were prescribed 10 or more drugs.32 For patients with at least six conditions, these values increased to 48% and 42%, respectively. Polypharmacy is associated with drug related morbidity such as adverse drug events, potentially inappropriate prescribing, and reduced drug adherence.8 The prevalence of polypharmacy is increasing, owing largely to changes in population demographics and increasing multimorbidity. A major difficulty for general practitioners is that many prescriptions are initiated by specialists but repeat prescribing occurs in primary care.8 Without clear communication it can be difficult to judge the rationale of drug treatment. Optimising drug regimens is an important component of care, and to achieve this regular drug reviews are required for patients with multimorbidity.8 The evidence for pharmacist led drug reviews for complex polypharmacy in the community is mixed.33-35 Close collaboration between pharmacists and doctors seems the most sensible approach for this patient group.

Drug reviews should encompass “deprescribing,” which involves stopping drugs that are not indicated, have inadequate prognostic benefit, or are causing side effects.36 Explicit prescribing criteria, such as the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) and the Screening Tool to Alert doctors to Right Treatment (START), can be useful in maximising the effectiveness of drugs.37 STOPP consists of 65 indicators of potentially inappropriate prescribing in older populations (aged ≥65 years), which have been validated in both hospital and community settings and have been found to be associated with adverse drug events.38 39 START comprises 22 evidence based prescriptions for long term conditions relevant to older people.40 For younger patients, the Prescribing Optimally in Middle Aged People’s Treatments (PROMPT) prescribing criteria have recently been developed. Although yet to be validated, these criteria are important steps in recognising and dealing with treatment burden in those aged less than 65 years.41

How can organisation and continuity of care be improved? Patients with complex multimorbidity often see many different healthcare providers working across multiple sites. Communication between providers is frequently suboptimal, which can impact negatively on patient outcomes.16 Changes in the delivery of general practice service have reduced the provision of continuity of care.42 43 Patients value continuity, with over 80% of older patients (aged ≥75 years) in a recent UK survey reporting a preference for seeing a particular doctor in their general practice.44 Continuity of care is also associated with improved outcomes, such as the delivery of preventive care and reduced preventable admissions.45 46 In a recent US study, higher levels of continuity were associated with lower rates of hospital and emergency department visits, lower complication rates, and less healthcare expenditure.47 General practitioners are uniquely positioned to provide the necessary relational, informational, and managerial continuity of care, and the importance of this function should not be underestimated.28 48 A great strength of primary care is the access it affords patients, and regular planned reviews may be helpful in “ordering the chaos” for this group.49 Another key aspect for general practitioners is rationalising specialist referrals and considering the components of secondary care that will have most impact on patients’ wellbeing. Clinicians are encouraged to identify patients as having complex multimorbidity and adopt a practice policy of continuity of care for these patients by assigning them a named doctor. Identification is not straightforward: the most common research definition of multimorbidity (the presence of ≥2 conditions) will identify large numbers of patients, many of whom will not have particularly complex needs. Evidence is lacking to guide practice in this area, but groups with multimorbidity and demonstrably higher care needs include patients with “complex” multimorbidity, defined as three or more chronic conditions affecting three or more body systems50; patients with comorbid physical conditions and depression51; patients prescribed 10 drugs or more8 52; and patients who are housebound or resident in nursing homes. Practices could also consider running specific multimorbidity clinics that address common clusters of conditions, as there is evidence that targeting risk factors common to comorbid conditions such as diabetes, heart disease, and depression is effective,30 and this would also reduce treatment burden for patients as they would need less frequent visits.19 Currently it may not be easy for practices to identify

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such patients and this is a priority for general practice software systems.

What measures can be used to promote patient centred care? Shared decision making Shared decision making has been defined as “an approach where clinicians and patients share the best available evidence when faced with the task of making decisions, and where patients are supported to consider options, to achieve informed preferences.”53 Research shows that shared decision making improves patients’ knowledge about their condition and treatment options, increases patient satisfaction with care, and improves patient self confidence and self care skills.54 In the context of multimorbidity it is first important to elicit what matters most to the patient. Asking this at the outset of the consultation allows the rest of the consultation to be utilised most effectively. A recent model has been proposed to support clinicians in implementing shared clinical decision making in clinical practice.55 This concerns three key steps: firstly, “choice talk,” which refers to the step of making sure that patients know that reasonable options are available, “option talk,” which refers to providing more detailed information about options, and “decision talk,” which relates to supporting the work of considering preferences and deciding what is best. A range of online shared decision making tools is also available to support this process.56

Another tool named the “Adriadne principles” has recently been developed to support decision making specifically during general practice consultations involving multimorbidity.57 This model places the setting of realistic treatment goals at the centre of the multimorbidity consultation and this is achieved by a thorough interaction assessment of the patient’s conditions, treatments, consultation, and context; the prioritisation of health problems that take into account the patient’s preferences; and individualised management to determine the best options of care to achieve these goals. In practice, asking a patient at the outset of a consultation “What is bothering you most?” or “What would you like to focus on today?” can help prioritise the management of aspects of care that will have the most impact for patients. Once patient priorities are identified, using available shared decision making tools may help support the process.

Self management in patients with multimorbidity Some evidence supports lay led self management education programmes for single chronic diseases in improving certain outcomes, such as self efficacy and self rated health.58 The evidence for such an approach with multimorbidity is, however, mixed.30 Patient preference should guide the utilisation of lay led self management groups. The evaluation of the UK expert patient programme showed improved self efficacy and energy levels at six month follow-up but no reduction in healthcare utilisation.59 In a recent randomised controlled trial in the United Kingdom general practice staff were trained about available resources, including an assessment tool for the support needs of patients, guidebooks on self management, and a web based directory of local resources. At 12 month follow-up there were no reported

improvements in shared decision making, self efficacy, or generic health related quality of life.60

What can be achieved in a 10 minute consultation? Internationally, general practitioners have highlighted lack of time as a barrier to providing care for patients with multimorbidity.61 62 Some evidence suggests that longer consultations result in more preventive health advice, less prescribing, and increased patient satisfaction rates.63 However this review was limited by the inclusion of only five older studies with short term follow-up. In deprived areas, increased consultation times have been shown to increase patient enablement and reduce general practitioners’ stress.64

With demand for general practitioner services increasing, it is difficult to schedule extra consultation time for patients with multimorbidity. Practices may decide to flag certain patients with complex needs to allocate longer routine consultation times, or arrange “specific extended consultations” to allow protected time on occasion to review chronic disease management and drugs. Having robust practice systems in place to ensure appropriate monitoring with the practice nurse before the appointment with a general practitioner would facilitate the most efficient and effective use of both patients’ and doctors’ time. Practice nurses or other multidisciplinary team members can contribute in specific ways, including undertaking target assessment of chronic disease and psychological or functional capacity assessments that can support doctor and patient shared decision making. Multidisciplinary input is an essential component of care for these patients, and referrals to relevant disciplines should be arranged when indicated and available.

Contributors: All authors contributed to the development, content, and practice points presented in this article, and all agreed on the final version. EW wrote the manuscript. SS is the guarantor. Funding: EW is funded by the Health Research Board (HRB) of Ireland under the research training fellowship for healthcare professionals award (HPF/2012/20). This review was conducted as part of the HRB PhD scholars programme in health services research (PHD/2007/16) at the HRB Centre for Primary Care Research (HRC/2007/1). Competing interests: We have read and understood the BMJ policy on declaration of interests and declare that: BG is the chair of the National Institute of Health and Care Excellence Guideline Development Group for “Multimorbidity: clinical assessment and management.” The views and opinions expressed are those of the authors, and do not represent NICE. CS has received fees as an external speaker on the topic of multimorbidity for the Ministry of Health in Singapore and has a role in the Royal College of General Practitioners in the United Kingdom, which includes consideration of care for multimorbidity. Provenance and peer review: Not commissioned; externally peer reviewed.

1 Fortin M, Bravo G, Hudon C, Vanasse A, Lapointe L. Prevalence of multimorbidity among adults seen in family practice. Ann Fam Med 2005;3:223-8.

2 Fortin M, Bravo G, Hudon C, Lapointe L, Dubois MF, Almirall J. Psychological distress and multimorbidity in primary care. Ann Fam Med 2006;4:417-22.

3 Fortin M, Lapointe L, Hudon C, Vanasse A, Ntetu AL, Maltais D. Multimorbidity and quality of life in primary care: a systematic review. Health Qual Life Outcomes 2004;2:51.

4 Condelius A, Edberg AK, Jakobsson U, Hallberg IR. Hospital admissions among people 65+ related to multimorbidity, municipal and outpatient care. Arch Gerontol Geriatr 2008;46:41-55.

5 Bayliss EA, Bayliss MS, Ware JE Jr, Steiner JF. Predicting declines in physical function in persons with multiple chronic medical conditions: what we can learn from the medical problem list. Health Qual Life Outcomes 2004;2:47.

6 Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, et al. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev 2011;10:430-9.

7 Gandhi TK, Weingart SN, Borus J, Seger AC, Peterson J, Burdick E, et al. Adverse drug events in ambulatory care. N Engl J Med 2003;348:1556-64.

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Questions for future research

What is the role of complex interventions to improve function in multimorbidity? The UK National Institute for Health Research is examining a complex intervention for multimorbidity patients in general practice (http: //public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=16067). The intervention is a coordinated three dimensional review of multimorbidity and includes the assessment of quality of life, patients’ priorities and disease measures, the identification and treatment of depression, and measures relating to simplification of drug regimens and adherence What is the role of integrated chronic disease prevention and management in patients with multimorbidity? In Canada, the Patient-Centred Innovations for Persons with Multimorbidity (PACE) team is developing and testing interventions of integrated chronic disease prevention and management for patients with multimorbidity in primary care (http://crmcspl-blog.recherche. usherbrooke.ca/?p=716) Will extended general practice consultation times improve outcomes for people with multimorbidity? The ongoing Scottish CARE PLUS randomised controlled trial, which is examining a general practice system-wide approach, including extended general practitioner consultation time, to improve outcomes for people with multimorbidity living in deprived areas will add to the limited evidence base in this area

Additional educational resources

Resources for healthcare professionals Medicines optimisation: helping patients to make the most of medicines. Good practice guidance for healthcare professionals in England (www.rpharms.com/promoting-pharmacy-pdfs/helping-patients-make-the-most-of-their-medicines.pdf)—This guide, developed as a collaboration between patients and practitioners, describes four principles of medicines optimisation American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity. Guiding principles for the care of older adults with multimorbidity: an approach for clinicians. J Am Geriatr Soc 2012;60:E1-25 (www.guideline.gov/content.aspx?id=39322)—This guide summarises the evidence for clinicians in managing older patients with multimorbidity across five domains; patient preferences, interpreting the evidence, prognosis, clinical feasibility, and optimising therapies and care plans

Resources for patients US Department of Health & Human Services. Agency for Healthcare Research and Quality. Questions to ask your doctor (www.ahrq. gov/patients-consumers/patient-involvement/ask-your-doctor/index.html)—Tips for patients to get the most out of their doctor appointments Ottawa Health Research Institute. Ottawa personal decision guide (http://decisionaid.ohri.ca/decguide.html)—A resource to support patients in making decisions about their health

8 Duerden M, Avery T, Payne R. Polypharmacy and medicines optimisation. King’s Fund, 2013.

9 Guthrie B, McCowan C, Davey P, Simpson CR, Dreischulte T, Barnett K. High risk prescribing in primary care patients particularly vulnerable to adverse drug events: cross sectional population database analysis in Scottish general practice. BMJ 2011;342:d3514.

10 Gallacher K, May CR, Montori VM, Mair FS. Understanding patients’ experiences of treatment burden in chronic heart failure using normalization process theory. Ann Fam Med 2011;9:235-43.

11 O’Brien R, Wyke S, Guthrie B, Watt G, Mercer S. An ‘endless struggle’: a qualitative study of general practitioners’ and practice nurses’ experiences of managing multimorbidity in socio-economically deprived areas of Scotland. Chronic Illn 2011;7:45-59.

12 Gunn JM, Ayton DR, Densley K, Pallant JF, Chondros P, Herrman HE, et al. The association between chronic illness, multimorbidity and depressive symptoms in an Australian primary care cohort. Soc Psychiatry Psychiatr Epidemiol 2012;47:175-84.

13 Salisbury C, Johnson L, Purdy S, Valderas JM, Montgomery AA. Epidemiology and impact of multimorbidity in primary care: a retrospective cohort study. Br J Gen Pract 2011;61:e12-21.

14 Barnett K, Mercer S, Norbury M, Watt G, Wyke S, Guthrie B. The epidemiology of multimorbidity in a large cross-sectional dataset: implications for health care, research and medical education. Lancet 2012;380:37-43.

15 Violan C, Foguet-Boreu Q, Flores-Mateo G, Salisbury C, Blom J, Freitag M, et al. Prevalence, determinants and patterns of multimorbidity in primary care: a systematic review of observational studies. PLoS One 2014, 9:e102149.

16 Sinnott C, Mc Hugh S, Browne J, Bradley C. GPs’ perspectives on the management of patients with multimorbidity: systematic review and synthesis of qualitative research. BMJ Open 2013;3:e003610.

17 Bodenheimer T. Coordinating care—a perilous journey through the health care system. N Engl J Med 2008;358:1064-71.

18 Tinetti ME, Bogardus ST Jr, Agostini JV. Potential pitfalls of disease-specific guidelines for patients with multiple conditions. N Engl J Med 2004;351:2870-4.

19 May C, Montori VM, Mair FS. We need minimally disruptive medicine. BMJ 2009;339. 20 Mercer SW, Watt GC. The inverse care law: clinical primary care encounters in deprived

and affluent areas of Scotland. Ann Fam Med 2007;5:503-10. 21 Drewes YM, den Elzen WP, Mooijaart SP, de Craen AJ, Assendelft WJ, Gussekloo J.

The effect of cognitive impairment on the predictive value of multimorbidity for the increase in disability in the oldest old: the Leiden 85-plus Study. Age Ageing 2011;40:352-7.

22 Glynn LG, Valderas JM, Healy P, Burke E, Newell J, Gillespie P, et al. The prevalence of multimorbidity in primary care and its effect on health care utilization and cost. Fam Pract 2011;28:516-23.

23 Wyatt KD, Stuart LM, Brito JP, Carranza Leon B, Domecq JP, Prutsky GJ, et al. Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review. Med Care 2014;52(Suppl 3):S92-s100.

24 Zulman DM, Sussman JB, Chen X, Cigolle CT, Blaum CS, Hayward RA. Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials. J Gen Intern Med 2011;26:783-90.

25 Fortin M, Dionne J, Pinho G, Gignac J, Almirall J, Lapointe L. Randomized controlled trials: do they have external validity for patients with multiple comorbidities? Ann Fam Med 2006;4:104-8.

26 Hughes LD, McMurdo ME, Guthrie B. Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity. Age Ageing 2013;42:62-9.

27 National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: treatment and management. (Clinical guideline 91.) 2009. www. nice.org.uk/guidance/cg91.

28 Roland M, Paddison C. Better management of patients with multimorbidity. BMJ 2013;346:f2510.

29 Lin EH, Katon W, Von Korff M, Tang L, Williams JW Jr, Kroenke K, et al. Effect of improving depression care on pain and functional outcomes among older adults with arthritis: a randomized controlled trial. JAMA 2003;290:2428-9.

30 Smith S, Soubhi H, Fortin M, Hudon C, O’Dowd T. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst Rev 2012;4:CD006560.

31 Gitlin LN, Hauck WW, Dennis MP, Winter L, Hodgson N, Schinfeld S. Long-term effect on mortality of a home intervention that reduces functional difficulties in older adults: results from a randomized trial. J Am Geriatr Soc 2009;57:476-81.

32 Payne RA, Avery AJ, Duerden M, Saunders CL, Simpson CR, Abel GA. Prevalence of polypharmacy in a Scottish primary care population. Eur J Clin Pharmacol 2014;70:575-81.

33 Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M, et al. A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet 2012;379:1310-9.

34 Holland R, Desborough J, Goodyer L, Hall S, Wright D, Loke YK. Does pharmacist-led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta-analysis. Br J Clin Pharmacol 2008;65:303-16.

35 Holland R, Lenaghan E, Harvey I, Smith R, Shepstone L, Lipp A, et al. Does home based medication review keep older people out of hospital? The HOMER randomised controlled trial. BMJ 2005;330:293.

36 Steinman MA, Hanlon JT. Managing medications in clinically complex elders: “there’s got to be a happy medium”. JAMA 2010;304:1592-601.

37 Gallagher P, Baeyens J-P, Topinkova E, Madlova P, Cherubini A, Gasperini B, et al. Inter-rater reliability of STOPP (Screening Tool of Older Persons’ Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) criteria amongst physicians in six European countries. Age Ageing 2009;38:603-6.

38 Hamilton H, Gallagher P, Ryan C, Byrne S, O’Mahony D. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med 2011;171:1013-9.

39 Cahir C, Bennett K, Teljeur C, Fahey T. Potentially inappropriate prescribing and adverse health outcomes in community dwelling older patients. Br J Clin Pharmacol 2013;77:201-10.

40 Gallagher P, Ryan C, Byrne S, Kennedy J, O’Mahony D. STOPP (Screening Tool of Older Person’s Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. Int J Clin Pharmacol Ther 2008;46:72-83.

41 Cooper JA, Ryan C, Smith SM, Wallace E, Bennett K, Cahir C, et al. The development of the PROMPT (PRescribing Optimally in Middle-aged People’s Treatments) criteria. BMC Health Serv Res 2014;14:484.

42 Campbell SM, Kontopantelis E, Reeves D, Valderas JM, Gaehl E, Small N, et al. Changes in patient experiences of primary care during health service reforms in England between 2003 and 2007. Ann Fam Med 2010;8:499-506.

43 Sharma G, Fletcher KE, Zhang D, Kuo YF, Freeman JL, Goodwin JS. Continuity of outpatient and inpatient care by primary care physicians for hospitalized older adults. JAMA 2009;301:1671-80.

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44 Aboulghate A, Abel G, Elliott MN, Parker RA, Campbell J, Lyratzopoulos G, et al. Do English patients want continuity of care, and do they receive it? Br J Gen Pract 2012;62:e567-75.

45 Saultz JW, Lochner J. Interpersonal continuity of care and care outcomes: a critical review. Ann Fam Med 2005;3:159-66.

46 Nyweide DJ, Anthony DL, Bynum JP, Strawderman RL, Weeks WB, Casalino LP, et al. Continuity of care and the risk of preventable hospitalization in older adults. JAMA Intern Med 2013;173:1879-85.

47 Hussey PS, Schneider EC, Rudin RS, Fox DS, Lai J, Pollack CE. Continuity and the costs of care for chronic disease. JAMA Intern Med 2014;174:742-8.

48 Guthrie B, Saultz JW, Freeman GK, Haggerty JL. Continuity of care matters. BMJ 2008;337:a867.

49 Haggerty JL. Ordering the chaos for patients with multimorbidity. BMJ 2012;345. 50 Harrison C, Britt H, Miller G, Henderson J. Examining different measures of multimorbidity,

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BMJ 2015;350:h176 doi: 10.1136/bmj.h176 (Published 20 January 2015) Page 6 of 6

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