Christine Clark BSc, MSc, PhD
Pharmacists must make use of remote monitoring technology to improve pharmaceutical care to patients in their own homes, according to James McElnay (professor of pharmacy practice, School of Pharmacy, Queens University, Belfast). This would involve the use of telehealth technologies to provide care at the right place and time to make a difference, he continued.
Previous work in Northern Ireland has already demonstrated the value of clinical pharmacy services. For example, in one study, patients with chronic obstructive airways disease, who received structured pharmaceutical care over a 12 month period experienced significant improvements in symptom control, better adherence to medicines, fewer visits to the emergency department and fewer hospitalisations compared with those receiving usual care.
In another randomised study, the integrated medicines management project, hospital pharmacist actively managed patients’ medicines from the time of admission to discharge. This involved medicines’ reconciliation on arrival, monitoring of treatment and education about treatment changes during the hospital stay and prompt communication of the discharge prescription to both family doctors and community pharmacists. This scheme had a significant impact on the medication appropriateness index, which fell from 17.5 to 5.7 in the intervention group. Moreover, length of stay decreased by two days, and the rate of readmission was reduced such that for every 12 patients receiving the service, one readmission was prevented.
One way to make further improvements in health care is to make use of devices that allow home-monitoring of patients – so-called ‘connected health’. Measurements such as blood pressure, weight, and lung function can be sent to a central server and made available to doctors and pharmacists. So far, most connected health projects have not involved pharmacy input. “Manufacturers [of this type of technology] have generally failed to grasp the importance that patients place on personalised health care”, said Professor McElnay. Triage centres are usually staffed by anonymous health care personnel rather than someone that the patient knows and trusts, he noted.
The general scheme for connected health is that the patient monitors his condition using a device connected to a telephone or the internet. The data are sent to central hub or health professional’s office and reviewed; at this stage reminders can be sent for missing data. When abnormal results are seen action can be taken, such as dose adjustment or referral. Two such projects, involving pharmacy services are currently getting under way in Belfast.
The first project will be a randomised trial of remote monitoring of patients with heart failure and is being undertaken in collaboration with the University of Texas. Plans are now in place for pilot testing of a device that incorporates weighing scales with a stand and handle bars that allows monitoring of weight, body fluid and electrocardiogram (via sensors in the handle bars). A clinical pharmacist will be able to read the results on a secure server and contact the patient to take action, within agreed guidelines, if necessary. The second project, which is currently being piloted in four community pharmacies, involves patient management of blood pressure. Each patient will receive a laptop, an automated sphygmomanometer and a mobile phone. During the study they will receive twice-daily text reminder messages and/or bespoke video messages. Each evening patients will confirm their adherence to treatment and send a blood pressure reading via the internet. The sphygmomanometer is connected to the laptop by bluetooth. The community pharmacist will monitor the results and intervene if necessary.
In summary, Professor McElnay said that the connected health approach has the potential to integrate pharmacists in the health care team. Importantly, it could facilitate early intervention that could prevent hospitalisations, reduce complications, involve patients in their own care and reduce healthcare costs. However, there is no doubt that pharmacists must engage with this new technology both as practitioners and researchers and take the opportunity to control it at local level so that patients can speak to people that they know and trust.
Can pharmacogenomics improve outcomes?
As many as 40% of people with psychiatric disease do not respond to prescribed drugs and pharmacogenomics could have a key role in their management, Hans Mulder (Department of Clinical Pharmacy, Wilhelmina Hospital, Assen, The Netherlands) told the audience. In future, doctors could check a patient’s pharmacogenetic profile before prescribing.
There are particular problems for patients with psychiatric disease. It can be difficult to communicate with them and some actively avoid care. Diagnosis and treatment are hard to quantify and the drugs used have complex pharmacokinetic and pharmacodynamics. For example, antidepressants take six weeks to achieve their full therapeutic effect but adverse effects start immediately.
Ideally, genotyping should be easy to interpret and provide clinically relevant information for more than one drug. Pharmacodynamics can be influenced by variations in receptors and transporters, for example, variations in the 5HT2A (serotonin 2A) receptors affect the responses to paroxetine and mirtazapine. People with the CC variant are more likely to discontinue paroxetine treatment than those with the TC or TT genotypes, but mirtazapine handling is not affected. Variations in the serotonin transporter gene, 5HTTPLR also affect responses to treatment with paroxetine and mirtazapine – people with the LL variant tolerate paroxetine well but mirtazapine poorly. Detailed knowledge is required to be able to interpret this kind of information and it is doubtful that many pharmacists have this knowledge at present, said Dr Mulder.
Genotyping for pharmacodynamic responses is complex but genotyping for pharmacokinetic responses is relatively simple. The phenotypes can be identified by plasma levels of the drugs in question. For example, genetic variants of cytochrome p450 2D6 (CYP2D6), which is involved in the metabolism of many antidepressant and antipsychotic drugs, have been characterised. Amongst Caucasians, 6-10% are poor metabolisers and 1-10% are ultra-rapid metabolisers. It follows that up to 20% of patients will metabolise these drugs abnormally. One study of nortriptyline dosing showed that the majority of patients required daily doses of 100–300mg, but a small number of poor-metabolisers needed only 20-30 mg and ultra-rapid metaboliser required 750mg. Many drugs are metabolised by CYP2D6, including risperidone, aripiprazole, fluoxetine, metoprolol, tramadol and oxycodone, added Dr Mulder.
In the general population about 20% of people are taking at least one drug metabolised by CYP2D6 but amongst patients with psychiatric (including geriatric and psychogeriatric) disease this rises to 50%. Genotyping for CYP2D6 is a worthwhile activity because only four need be tested in order to find one patient who would need dose modification, explained Dr Mulder.
In Dr Mulder’s hospital a pharmacogenetic service has been in operation since 2006. Test for CYP2D6 and CYP2C19 are available and the results can be provided in one week. The results are explained to the prescriber – especially for poor metabolisers and ultra-rapid metabolisers with CYP2D6, said Dr Mulder. Advice is based on the Dutch therapeutic guidelines for genotype dose modifications. In 2011 the Scientific Institute of Dutch Pharmacists (WINAp) published a new guideline that covers 53 drugs, 25 of which are metabolised by CYP2D6.
Dr Mulder cited the example of a patient who was taking fluvoxamine, metoclopramide and codeine. The patient had a plasma fluvoxamine level of 365microg/ml (normal range 100-250) and was experiencing poor pain relief and bradycardia. Pharmacogenetic testing showed that he was a CYP2D6 poor-metaboliser and this enzyme is responsible for metabolising all three drugs.
In this case, both fluvoxamine and metoprolol were being metabolised too slowly and so the patient was effectively overdosed, whereas the codeine was not being converted to morphine and was therefore not delivering effective pain relief. When his treatment was changed to sertraline, atenolol and morphine, the problems were solved. The pharmacogenetic service was called 1200 times in 2010 with dosing queries and this accounts for 0.5 full-time equivalent member of staff. “This has got us recognised as part of the patient care team”, said Dr Mulder.
As yet, genotype-based dose modification is not widely practised and one of the reasons given for this is that there is no good evidence to support it. However, the level of evidence for pharmacogenetic dose adjustment is better than for dose adjustment in renal failure, said Dr Mulder.
Children and the elderly
Children and the elderly represent special populations and it is at the extremities of life that pharmacists can have the biggest input, argued Steve Tomlin (consultant paediatric pharmacist, Evelina Children’s Hospital, London). Children are particularly challenging; there can be a two-three fold variation in the weights of adults but in children the variation can be 200-fold, he continued. In addition, drug-handling differs from that in adults, for example, the half life of diazepam in adults is 10-12 hours but in a 24-week old neonate it is 80 hours.
Important questions are, “when does a child become an adult?” (for dosing purposes) and, “when can a dose be rounded up or down?”. Sometimes the licensing provisions further complicate the situation, for example, the adult dose of intravenous aciclovir is 10 mg/kg (for immunocompromised patients) and the paediatric dose in 500mg/m2. This can result in an 11-year old patient getting twice the dose that a 12-year old would have, said Mr Tomlin.
In the EU more than 50% of medicines used in children have never been tested in children. A survey in 2003 showed that 80% of medicines used in neonatal intensive care were unlicensed and 40% of medicines used in paediatric intensive care were unlicensed.
The medicines that are used need to be right for the population being treated. Sometimes the product is too concentrated, for example, one survey showed that in a unit 31% of prescriptions required less than 1/10th of a vial to give the correct dose and nearly 5% required less than 1/100th. Another problem can be unsuitable excipients. Benzyl alcohol, present in amiodarone and lorazepam injections, can cause gasping syndrome in infants. Ibuprofen injection contains lignocaine and is therefore not suitable for treatment of patent ductus arteriosus.
There can also be problems with oral formulations, said Mr Tomlin. For example, phenobarbitone elixir contain 38% alcohol which can result in the patient receiving an unacceptably large amount of alcohol. It is important to be aware of the difference between dispersible and soluble dosage forms – when dispersible products are used much of the dose can be lost.
In conclusion, Mr Tomlin said that most research in medicines related to the general adult population and little information is available for the population extremes but this is where pharmaceutical expertise can play an important part.
The challenge of intellectual disability
Patients with intellectual disability (ID, also known learning difficulties or mental retardation) represent a particular challenge for effective drug treatment, according to Martin Henman (senior lecturer in the Practice of Pharmacy, Trinity College, Dublin).
ID is associated with many of the diseases seen in the general population but the age of onset is often earlier. For example, dental disease is common and the pain and discomfort can lead to feeding difficulties. In addition the rate of ageing is faster than in the general population – a 50-60-year-old with ID is considered elderly. Mood, anxiety and adjustment disorders tend be under diagnosed in this group but psychotic disorders tend to be over-diagnosed. Dementia occurs in 12% of ID patients by the age of 50 compared with 34% of those with Down’s syndrome. Challenging behaviour, associated with aggression, over-activity and self-injurious behaviour occurs in 60% of ID patients and antipsychotic drugs are commonly used to treat the condition.
People with ID have poor coping skills and consequently are very vulnerable to stressful life events, for example, the death of a parent, that can trigger behaviour disorders.
Turning to the quality of care with medicines, Dr Henman said that no formal studies have looked at the use of medicines for these conditions and they are rarely listed on the SPCs for medicines.
A systematic review of the use of antidepressants suggested that about 50% of patients would benefit from selective serotonin reuptake inhibitors (SSRIs). Studies with mood stabilisers and anti-epileptics were mostly “riddled with methodological problems”, according to one reviewer, although lithium could be of benefit to some patients. A Cochrane review of the use of antipsychotics concluded that there was no evidence of help or harm for ID patients and the consensus view is that antipsychotics should be used as a last resort, said Dr Henman.
People with ID have substantial health care needs but they receive less pharmaceutical care than any other group of patients. They receive more medicines than almost any other group of patients and they start taking them at an early age. In addition, their pharmacodynamic and pharmacokinetic responses are more variable than most.
Pharmacists involved in the care of these patients should take steps to manage the polypharmacy that is feature of their treatment, recommended Dr Henman. This should involve a review of indications, doses and effectiveness every three months together with checks for adherence and for signs of adverse drug reactions.
Where appropriate laboratory tests should be closely monitored, for example for liver and renal function. Pharmacists should also ensure that care-givers understand appropriate use of all medicines – prescribed, non-prescription, as-needed and herbal or alternative medicines.
Doing more for less
The average performance in health systems compared to the best suggests 15-20% saving is usually feasible without damaging care, according to Charles Normand (Edward Kennedy Professor of Health Policy and Management, Trinity College Dublin). Moreover, the annual scope for gains is 2–4%; “It is feasible – it only a matter of doing it”, he added.
Performance can be improved by pure efficiencies, such as utilising the time spent waiting for some thing else to happen. It can also be improved through the use of new technologies or through new ideas or understanding, which Professor Normand described as “doing it differently”. Of these three approaches, the last one is probably the most important, he said.
“It is often said that costs will rise because of technological development but this is nonsense – technology can only reduce or maintain costs”, said Professor Normand. New technologies can shorten the treatment time, shorten the stay in hospital, speed the recovery time, or reduce incorrect diagnoses. They can also increase the scope of what can be done. If technology is badly used it will increase costs, for example, if a device is used for two hours per day instead of 18 hours per day. Well-known examples include the use of short-course chemotherapy for tuberculosis instead of months in a sanatorium and transurethral resection of the prostate instead of open prostatectomy.
Turning to new ideas and understanding, Professor Normand said that changes in skill mix were important steps. Examples of this included greater use of assistants and technicians such as dental hygienists and operating theatre technicians and more use of allied health professionals in place of doctors. “Could the idea of a doctor be past its sell-by date?” he asked. Another important step was the use of available technology to handle tasks differently. Remote monitoring and diagnostics, and e-prescribing and drug management were examples of this.
Changes in the configuration of the health services were possible and this has been evident in the way that some services have been moved closer to patients; for example, some consultations now take place entirely through communication over the telephone. Another key change is the use of electronic records. This is not just a change from paper to electronic records – it has also made possible the pro-active management of some chronic diseases. For example, it is possible to identify patients on multiple treatments and, with a few keystrokes, call them up for review.
There is good evidence that good building design can save money (in healthcare) as the cost of buildings is never more than 10% of the costs of care, said Professor Normand. Having the right technology and investing in the right skills can also save money but we tend to use the wrong buildings with the wrong equipment and with staff with too few or the wrong skills, he added.
Paradoxically, the current economic recession might help to make some of the changes that are needed by producing a degree of destabilisation. In the long run it is easier to adapt frequently and rapidly rather than let old ideas and approaches persist, he concluded.
MRSA in nursing homes
A survey of antimicrobial prescribing in nursing homes in 17 European countries showed that the highest rates were in Northern Ireland, Finland and the Czech Republic. Michael Tunney (Queen’s University, Belfast, Northern Ireland) explained that the overall mean prevalence of antimicrobial prescribing was 6.5% in April and 5% in November. There was wide variation ranging from 1.4% in Germany and Latvia to 19.4% in Northern Ireland in April. The main indications for antimicrobials in Northern Ireland were treatment and prevention of urinary tract infections and treatment of respiratory tract infections.
Coupled with the high rates of antimicrobial prescribing were high rates of colonisation of staff and patients with methicillin-resistant Staphylococcus aureus. A 2009 study reported prevalence rates of 23.3% for residents and 7.5% for staff. Dr Tunney called for specific guidelines for antimicrobial use in nursing homes and increased accountability for antibiotic prescribing.