Thinking outside the (dosette) box: Professional support for medicines management at home for patients approaching the end of life. A qualitative study CURRENT STATUS:

Background: The management of medicines towards the end of life can place increasing burdens and responsibilities on patients and families. This has received little attention yet it can be a source of great difficulty and distress patients and families. Dose administration aids can be useful for some patients but there is no evidence for their wide spread use or the implications for their use as patients become increasing unwell. Aim: To explore how healthcare professionals describe the support they provide for patients to manage medications at home at end of life. Methods: Qualitative interview study with thematic analysis. Participants were a purposive sample of 40 community healthcare professionals (including GPs, pharmacists, and specialist palliative care and community nurses) from across two English counties. Results: Healthcare professionals reported a variety of ways in which they tried to support patients to take medications as prescribed. While dose administration aids were useful for some they posed a number of practical difficulties. Other strategies described included: rationalising the number of medications; providing different formulations; explaining what medications were for and how best to take them; providing and supporting ways to record medication taking; and ways of balancing restricted access to controlled drugs and appropriate pain management for patients in the context of substance misuse and memory loss. Conclusions: The burdens and responsibilities of managing medicines at home for patients approaching the end of life has not been widely recognised or understood. This paper considers some of the strategies reported by professionals in the study, and points to the great potential for a more widely proactive stance in supporting patients and family carers to understand and take their medicines effectively. By adopting tailored, and sometimes, ‘outside the box’ thinking professionals can identify immediate, simple solutions to the problems patients and families experience with managing medicines.

between patient and family caregiver (FCG), between families and HCPs, and between HCPs is fundamental to identifying and managing any issues with medication 9. Providing clear information about medications and undertaking regular reviews were also central elements that promote and support medicines management (8, also see 1). There are a number of dose administration aids see Box 1 and technologies available for patients and FCGs to support management and administration.
Multi-compartment compliance aids can be extremely useful for some but do have a number of limitations 10, 11 and there is currently insufficient evidence to support their widespread use 7, 12, 13.

_________________________________________________________________ Box 1: Dose administration aids
Such as: mobile phone applications for reordering prescriptions, alarms, timer dispensers, lock boxes, pharmacy pre-packaged blister packs and, most commonly simple pill organisers such as dosette boxes Dosette boxes -re-useable containers typically filled by patients. (The term 'dosette box' has multiple spelling options in the UK (dosette, dosset, dossete, dosett) and is based on the registered trade mark 'Dosett' by a Swedish Company for a 'plastic container for dispensing drugs'. We will use the spelling 'dosette' as this is most common in the UK and used by the NHS.) Blister packs -disposable bubble packs containing designated sealed compartments for medicines to be taken at particular times of the day There is a lack of consistency of terms used in the literature to describe dose administration aids.
These included pill organisers, dosette boxes®, blister packs, Monitored Dosage System (MDS), Multi-compartment Compliance Aid (MCA) and various branded versions such as Medisure® and Nomad® 7 . HCPs in this study often used the terms dosette box and blister pack interchangeably.

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Research into older age, including the impact of dementia, is contributing to our knowledge about the role patients and FCGs must take on in order to manage medications 1,5,14,15 . This work has identified that patients often have to cope with complex regimes and require considerable support from FCGs. Managing medications when someone is seriously ill and dying at home can generate additional issues. However, little attention has been paid to the context of palliative and end of life care. As patients become increasingly unwell they often require frequent and irregular changes to their medication regimes. This may include stopping some long-term preventative medicines such as statins, but increasing others such as those for pain and nausea [see Box 2 on Polypharmacy and deprescribing]. Patients may begin to struggle with swallowing standard tablets and medications may be dispensed in other forms such as patches, liquids or sublingually.

Box 2: Polypharmacy and deprescribing
Polypharmacy: taking of multiple medications. It is recognised that all medications can have side effects. Adverse reactions are more likely as the number of medications increase, and there is greater risk of patients being unable to take medications as prescribed. Such 'potentially inappropriate medications', or 'problematic polypharmacy' 16 is common in palliative care 17 and ultimately has a cost to both patients and the wider community [18][19][20] .
Deprescribing: 'the process of tapering, withdrawing, discontinuing or stopping medicines to reduce potentially problematic polypharmacy, adverse drug effects and inappropriate or ineffective medicine use by regularly re-evaluating the ongoing reasons for, and effectiveness of medication therapy' 21 ______________________________________________________________________________________________ In their different roles HCPs engage with patients and families in a variety of ways, in clinics, pharmacy/community settings and in their own homes allowing them to identify practical day-to-day issues and offer support. This paper draws on a set of findings from a wider National Institute of Health Research funded UK study to explore the management of medications for patients who are approaching end of life. We report on how HCPs described the way in which they supported patients and families to manage medications in their homes.

Study design
Qualitative study involving semi-structured in-depth interviews.

Setting
The study is set in two English counties. Both are diverse in levels of affluence, age, ethnicity and population density, with both rural and urban areas. In both regions there are generalist and specialist teams providing palliative and end of life care.

Participants
Participants included 40 community professionals from a range of roles, including: General practitioners (GP), specialist palliative care nurses, community nurses and both GP-and communitybased pharmacists (see Table 1). Participants were recruited using purposive and snowballing techniques across the two counties via GP practices and specialist palliative care services. Each was invited via letter, email or face to face contact and given an information sheet and contact details of the research team if they wished to participate.

Data collection and recording
Interviews took place between June 2017 and October 2018. The majority of participants were interviewed on a one-to-one, face-to-face basis by EW, GC and KP at their place of work. However, we were receptive to workload constraints and participant preferences so undertook four interviews over the telephone, one joint interview, and three group interviews (involving three or more participants).
All participants gave written or, in the case of telephone interviews, verbal consent. All interviews were audio recorded and notes written up after the interview took place. The focus of the interviews was to explore what HCPs saw the issues to be for patients and families managing medications at home as the patient approached the end of life, and how they sought to support such patients and families in managing their medications. HCPs were asked to think of a current or recent case which had posed issues for medicines management or where this had worked well. They were then asked to situate this case within their normal practice to establish how common or rare particular issues might be.

Analysis
All interviews were transcribed verbatim and fully anonymised before transcripts were uploaded to Nvivo12© and coded. Using a process of thematic analysis EW, GC and KP reviewed codes and undertook condensing and sorting. The legitimacy of categories was reviewed with the project steering group. Several transcripts were also read and coded by our PPI co-applicant (Alan Caswell) for an additional perspective, transparency and comparison. Each transcript was coded by two team members and three were triple coded. Once coding was complete, nodes were further interrogated and refined to generate node summaries of key themes illustrated by quotations from transcripts.

Results
The majority of HCPs acknowledged that patients did not always take medications as prescribed and many reported trying to explore how to resolve this with patients and families. Dosette boxes, and more commonly 'blister packs', were prepared by pharmacists, and often delivered directly to patients' homes. These were offered and perceived as a problem solving intervention to help patients to organise and remember when to take their medicines. In a number of cases these boxes could be helpful and appropriate. However, HCPs recognised that some patients and families needed more comprehensive and innovative approaches. Here we discuss the strategies described by HCP participants in the study who were thinking 'outside the box' in order to help support patients overcome the practical difficulties of managing their medications in the home environment. This insight from a community nurse illustrates the underpinning issues:

Dosette boxes and blister packs
Dosettes and blister packs were often seen as an effective strategy in eliminating any confusion about what tablets to take when. HCPs viewed them as an important tool and appropriate way to support patient's wishes to continue to manage at home independently: We've got a high incidence of dementia as well in the area. So what we've done, as a pharmacy team, is we've put everybody into, that we feel are vulnerable, with their consent, obviously … dosette boxes where we dispense the medication into morning, lunchtime, evening, bedtime.

(HCP20_Pharmacist)
A few respondents observed that this system was sometimes put in place for the convenience of paid Home Care Workers enlisted to prompt patients to take medication in the home. However, this could potentially undermine agency and competence, detaching patients from the process by 'making people further removed from taking responsibility of their own medication' (HCP05_Community nurse). They also made it difficult, if not impossible, for patients to identify individual tablets.
One of the recognised issues with pre-prepared blister packs is that they do not accommodate all types of medication. Consequently, patients might have to take additional medications, such as liquids or tablets prescribed to be taken 'as needed', alongside the allocated pills from the box. In addition, box contents are usually made up for a month, and cannot be easily altered if medication is changed during this period: HCPs cited concerns around the wastage of medications when boxes needed to be altered during the month's prescribed supply in which case the rest of the medications in the box had to be disposed of.
HCPs also identified potential problems with pain medications where patients who are unaware of, or unable to identify the contents, may risk taking more pain relief than they need if they are also taking 'as needed' doses on top of those included in their dosette box. This was a particular issue when changes were made to medication regimes. For these issues taking some time to explain, and implementing a simple memory aid system, could be extremely effective. HCPs also reported using items such as lockable tins for patients who could not safely manage their own medications, or where there was potential for misuse or misappropriation of medication, and dispensers with timing devices or alarms for those with impaired memory. Some reported changing the route of administration for a patient when swallowing tablets became an issue or when the number of tablets added to the burden of medicines management. One community nurse felt alternative administration routes also supported adherence as they did not hold the same negative connotations as 'pills' and 'tablets'.

I get on well with other forms of medication, because sometimes, like a buccal … or a patch, that can be an easier way for someone to actually accept receiving the medication rather than taking everything orally. (HCP06_Community nurse)
In a small number of reported instances, HCPs recognised that their input was needed on a more consistent basis to support medication use. A few HCPs reported telephoning patients to remind them of recent changes to their medications. One HCP narrated an instance with a patient with memory issues who was repeatedly coming to hospital with heart failure symptoms because he was not remembering to take his medication. They subsequently rationalised this to be taken once a day and arranged for a community nurse to visit daily to prompt this administration. However, lack of time to adequately discuss and monitor medicines and related issues was acknowledge to be a limitation, and this level of input was unlikely to be routinely available.
Recognition, and support for, patient choices about their treatment and care was a strong theme throughout the interviews. A number of HCPs described the considerable effort they were prepared to make to enable these, regardless of whether they considered them to be wise options.

So she'd developed swallowing issues. And so we tried liquid medication, she didn't like it. … So she went back to taking oral tablets. … And then I can think about an incident, it was interesting, at the hospice, where I got a phone call from the staff nurse saying the carers had said that she'd had a
choking episode following taking tablets in the morning, and that, at the hospice, they weren't going to be prepared to give her tablets any longer. … I said, 'This isn't an issue, this lady has capacity to make the decision, she doesn't want to take liquid medication, she wants to take her tablets, the risks have been explained to her'. (HCP05_Community nurse) Tailored solutions were particularly required in difficult and unusual situations, for example where patients or someone in their household were affected by phobias, addictions, substance abuse or the effects of dementia. One palliative care nurse described how she and her colleagues were working to find constructive and creative ways to manage pain for a patient who was determined to die at home.
As the patient, his FCG and their circle of friends had issues with substance misuse, safeguards were put in place to limit the amounts of morphine they could access at any one time.
We just introduced the patch last week, he was using a lot of the Oramorph, … he's used the Oramorph less since the patch has gone on. …We always put dates on the bottle and the box. So we can see which bottle he's still using and which box, and keep an eye on it as well. He knows we do

that. (HCP07_Specialist Palliative Care nurse)
This HCP also recalled a patient who expressed a fear of needles and refused any injectable medications. In the quote below the HCP described trying to balance respecting the patient's choice and agency and providing effective care: There were few references to pharmacists taking on roles to support medicines management or to other HCPs identifying the potential for greater pharmacy integration in the healthcare team.

Discussion
The paper has explored ways in which HCPs in a UK study reported thinking 'outside the box' in order to support patients and families with medication needs. Some expressed resignation that patients often failed to, could not or did not want to take their medications as prescribed. However, participants described sometimes going to considerable lengths to support patients and seek ways to help them to take medications in an acceptable and effective way. HCPs in this study often focused on the prescription element of the process, aiming to ensure appropriate symptom control by undertaking simple changes to regimes and routes of administration. These adaptations often made a considerable difference to patients' ability to manage their medicines effectively. In other instances, HCPs reported having to be quite innovative, and explore a number of routes to help patients overcome the practical problems involved in organising and taking their medicines effectively.
Examples included writing the function of the tablets on the box, giving prompt cards, issuing medications on a limited basis to reduce stockpiling and misuse, providing visual aids and reinforcing information in writing or over the phone.
Patients living at home at the end of life often have complex medication regimes with large numbers of medications, different routes of administration, and high doses of controlled drugs. In line with the international literature, the HCPs participating in this study recognised the burdens of polypharmacy at end of life 17, 19, 22-24 , but did not always seem to acknowledge how the burdens of medication management added to the 'work' patients and FCG's were undertaking when someone is seriously ill in the home environment 25 . FCGs are also more likely to be older, and have reduced abilities and comorbidities of their own 26 . Until recently much of the literature on medication management focused on 'adherence' and 'compliance' and the implication for health outcomes 8,[27][28][29][30] . There is now a small but growing body of work that recognises the difficulties for patients 5 , their desire to limit the amount of medications they take as far as possible 2,3,19 and the burdens regimes can place on FCGs when a patient is dying at home 23,31,32 . Indeed, the international literature indicates that in other countries, particularly the United States and Australia, FCGs are regularly undertaking even more advanced tasks in administering sub-cutaneous medications prescribed for end of life symptoms 33-37 .
While there have been some moves towards this in the UK the feasibility of this approach is still being assessed 38, 39 .
While not aimed specifically at palliative care, current UK guidance 20,40 advocates for professionals to take account of individual patient needs, preferences for treatment, health priorities and lifestyle and recognise that 'medicines are likely to be just one aspect of a person's care' 40 . However, to date there has been little work to explore ways of supporting patients and families in medicines management in order to make their lives less stressful 7,41 .
The ability to maintain accurate medicine taking could be a critical factor in avoiding unscheduled hospital admissions and determining whether a patient could remain living at home 42-44 . This paper seeks to extend beyond the compliance/adherence discourse 45 to recognise the reasonable difficulties patients and families often face in managing complex regimes and how HCPs might help them overcome these 8 . HCPs in this study often reported encouraging the use of simple dose administration aids such as dosette boxes and blister packs. These can be extremely useful and can support patients to remain at home by helping them to manage their own medication. They can also be a useful tool in supporting Home Care Workers to safely prompt and administer medications in patients' homes [10][11][12]46 . Conversely, these aids can have negative implications for a person's independence and agency when they disempower patients by removing responsibility for, and understanding of, their own medications 47 . They also have practical disadvantages when, as is common in end of life care, medications need to be changed rapidly and frequently 10 . This increases risk of adverse events, lack of effective symptom management, and instability of some medications when stored outside their original packs. The result is often considerable wastage of pre-prepared boxes or multiple additional medications which are not included in the box or blister pack 46 . These types of issues add to the challenge of optimising pain control in the home environment 48,49 .
Our findings further echo those of current literature in that the majority of participants rarely recognised the current or potential contribution of pharmacists as part of the palliative care team 50-54 , and the community pharmacy services designed to improve patients' knowledge of medicines and use 9,55,56 . Those that did recognise and refer to the role of pharmacists, were either based at, or working with, GP practices where pharmacy services were on-site. This proximity afforded closer relationships between pharmacists and GP/community nurses and a greater understanding of the benefits of additional services, such as, medication review clinics run by pharmacists in GP surgeries. This paper has demonstrated that there is scope for much greater understanding of the reality of patient and FCG experience, the difficulties they face, and the potential for HCPs to engage with innovative and tailored ways of supporting medicines management for seriously ill patients being cared for and dying at home.

Limitations
A strength of the study is that it represents the views of a wide range of HCPs, including pharmacists, working in diverse community healthcare services and geographic locations. However, the study location in two adjacent English counties means that the findings may not be typical of other settings.

Conclusions
If we move the discourse forward from one of compliance and adherence and recognise the reasonable, and often practical, difficulties patients and FCG face when managing medications we can look at ways in which HCPs can help them to overcome these issues. Medication reviews, reduction of problematic polypharmacy and the use of dose administration aids such as dosette boxes are some of the ways in which HCPs can support patients and families in medicines management at the end of life.
However, there may be times when HCPs need to 'think outside the box' in order to identify and support patients to safely, effectively and independently manage their medications. Availability of data and materials: The datasets generated and/or analysed during the current study are not publicly available as they are personal accounts of patients', families' and healthcare professional's experiences. It is essential that we maintain confidentiality and anonymity but sufficiently anonymised parts of the data are available from the corresponding author on reasonable request.

Competing interests:
The authors declare that there is no conflicts of interest.  Acknowledgements: We would like to acknowledge PPI co-applicant Alan Caswell for his overarching contributions to the study and for contributing to the analysis of the interview data in this paper.  *Specialist palliative care nurses -those working at a Band 6 or 7 level with additional training in palliative care. These may include: Clinical Nurse Specialists/Hospice at home nurses -these nurses provide advice and support to patients and families as well as having expertise in the management of symptoms. They may be assigned to work in patients' homes or with care homes. Macmillan Nurses -some specialist palliative care nurses are badged under the brand of 'Macmillan Cancer Support', a national cancer charity. These nurses focus on providing advice for the management of complex symptoms and/or psychological distress. **This is an overarching group of nurses working in the community including District nurses, Community Matrons and Clinical Nurse Specialists in non-palliative specialisms such as heart failure and neurological conditions. In the UK, qualified nurses' start at Band 5 and go up to Band 8. Nurses at Band 6 have advanced training, skills and experience; those at Band 7 have managerial roles in addition.

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