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Polypharmacy guidance document









Polypharmacy Guidance
October 2012
Developed by The Model of Care Polypharmacy Working
Group

Quality and Efficiency Support Team
Scottish Government Health and Social Care Directorates

Version 2 – controlled only when electronic – to be updated September 2013 Acknowledgements We would like to take the opportunity to acknowledge the following individuals and groups that have worked collectively to develop this guidance: Model of Care Polypharmacy Working Group:
Alpana Mair, Kate Wood, Martin Wilson, Miles Witham, Niles Michael, Graham
McPhee, John Cromarty,
Identification of Patients and Data for Improvement
Thomas Ross, Michelle Watt, Steve Kendrick, Mark Sanderson, Bruce Guthrie,
Noreen Downes, Joyce Mitchell, Alpana Mair, Libby Morris


In addition would like to thank the following groups and individuals for their in the input:
The Scottish Primary Care Advisors Group, iSPARRA team, LTCAS, Gregor Smith, Anne
Hendry, Joint Improvement Team, HIS, Steve Gilbert, Graham Kramer, and Simon Hurding.


Cover image: foto76 / FreeDigitalPhotos.net
Version 2 – controlled only when electronic – to be updated September 2013 Foreword
We are pleased to present the Polypharmacy Guidance for 2012. This is the first iteration of
a national approach to address the issues resulting from the use of multiple medicines in the
frail and elderly population. The aim is to improve therapeutic care by reducing the risk of
adverse drug reactions associated with polypharmacy.
The story of Pat provided by the Health and Social care alliance illustrates the problems that
can be faced by patients taking multiple medications and can be found at :

NHS Scotland has a very good track record in delivering high standards of care and the
safe, effective and efficient use of medication is no exception.
It is important to highlight that this report contains both management information for boards
to use locally and guidance information for clinicians to undertake the review.
Management information included is the evidence based rationale behind this approach to
addressing polypharmacy. In addition there is included a set of tools that can be used by
NHS Boards to form the guidance documents to allow clinicians to implement change.
It is recommended that the Polypharmacy Report 2012 is considered by boards for
Prescribing Action Plans.

We commend the information within this report to you, please use wisely and efficiently
Kind regards

Bill

Chief Pharmaceutical Officer
Chief Medical Officer
Version 2 – controlled only when electronic – to be updated September 2013 Contents


Version 2 – controlled only when electronic – to be updated September 2013 Section 1: General Principles
Version 2 – controlled only when electronic – to be updated September 2013 Why is reviewing polypharmacy important?

Medication is by far the most common form of medical intervention. Four out of five people
aged over 75 years take a prescription medicine and 36 per cent are taking four or more.
However, it is suggested that up to 50 per cent of drugs are not taken as prescribed, many
drugs in common use can cause problems and that adverse reactions to medicines are
implicated in 5 - 17 per cent of hospital admissions.
Research has demonstrated that patients on multiple medications are more likely to suffer
drug side effects and that this is more related to the number of co-morbidities a patient has
than age2. There is a clear and steady increase in the number of patients admitted to
hospital with drug side effects. Patients admitted with one drug side effect are more than
twice as likely to be admitted with another3. This can lead to a situation where adults may be
suffering side effects (that may even lead to hospital admission) from drugs that they derive
little or no benefit from, or where the harm of the drug outweighs any possible benefit.
Prescribers and pharmacists receive extensive guidance on the indications for starting
drugs, particularly drugs used in primary prevention. However, these guidelines are usually
based on evidence from narrow and often atypical populations, and almost exclusively focus
on single conditions.
In contrast, clinical care frequently involves balancing the recommendations of multiple
guidelines in people who have many different conditions These recommendations, often
focussed on starting treatment, are not balanced by comprehensive policy or guidance on
when it might be appropriate to stop medication. This may be especially relevant in people
with multiple morbidities prescribed large numbers of medications, in people particularly
vulnerable to adverse events or in those who are unlikely to obtain benefit in long-term
prevention due to life expectancy.
Before now, little guidance existed to assist prescribers in balancing the recommendations of
multiple (and potentially conflicting ) guidelines. This guidance aims to support primary care
practitioners undertaking comprehensive face-to-face medication reviews (defined as Level
3 Reviews) with patients and where appropriate carers/welfare proxies, particularly for
patients with cognitive impairment.
The general principles of what should be covered in a medication review are covered in
but decision making always needs to be tailored to an individual's circumstances
and preferences. Clinical tools and information that may help these decisions are included in
nformation that assists in the
planning and implementation of this guidance.
1 Quality and Outwork framework 2012 http://www.nhsemployers.org/Aboutus/Publications/Documents/QOF_2012-13.pdf 2 Co-morbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort study M Zhang et al BMJ 2009;338:a275 3 Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients M Pirmohamed et al, BMJ 2004;329:15-19 4 Epidemiology of multiple morbidity and impliocations for healthcare, research, and medical education: a cross-sectional study. Quality, safety and Informatics Research Group, University of Dundee. May10, 2012 DOI;10.1016/s0140-6736(12)60240-2 5 Patterson SM, Hughes C, Kerse N, Cardwell CR, Bradley MC. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database of Systematic Reviews 2012, Issue 5. Art. No.: CD008165. DOI:10.1002/14651858.CD008165.pub2 Version 2 – controlled only when electronic – to be updated September 2013 It is the clinical responsibility of the prescriber to assess the appropriateness of making
changes to a patients prescribed therapy. Prescribers need to be aware that patients with
frailty and or multiple co-morbidites are often excluded from clinical trials and as such the
benefit risk results may not be generalisable .
What should be happening under QOF?
As part of the GP contract, medication review is covered under medicines indicator 11 and
12, detail is shown below:

Medicines 11
A medication review is recorded in the notes in the preceding 15 months for
all patients being prescribed four or more repeat medicines (Standard 80%)
Medicines 12 A medication review is recorded in the notes in the preceding 15 months for
all patients being prescribed repeat medicines (Standard 80%)
The detailed guidance can be found
For frail adults, a level 3 medication review is recommended.
What is the aim of this guidance?
A multidisciplinary group from NHS Boards across Scotland, has developed guidance to
address polypharmacy. For membership, see covers key learning
from NHS Boards that have started to deliver polypharmacy reviews.
Prescribers are often faced with two often overlapping situations where extra thought and
consideration is needed:
When faced with a patient who is either on or has indications to be on multiple medications. When a patient is ‘frail' in a medical sense. ‘Frailty' in this guideline is taken to describe a state where a patient has a reduced ability to withstand illness without loss of function. This guidance aims to: Provide information about patient groups that NHS Boards should consider as a higher priority for polypharmacy review. Outline of a robust and pragmatic process of medication review in these patient groups. Provide NHS Boards with tools that can then be adapted for local use as guidance for clinicians undertaking the reviews; where possible relevant documentation and guidance has also been provided. It should be stressed to clinicians that this guidance should be read before carrying out reviews, rather than to be used as a checklist during reviews. It aims to provide background information to help clinicians conduct this level of medication review. 6 Rockwood CMAJ 1994; 150:489-495. Version 2 – controlled only when electronic – to be updated September 2013 When applying the tools, particular attention is drawn to high risk drug combinations and
medications that are known to be high risk in frail adults. It should be emphasised that
reducing doses and or frequency of high risk medicines may be useful where these cannot
be stopped completely. Patient safety is the core concern.
The frail elderly are a unique subgroup of patients within a subgroup. They probably
represent a phenotype at the extreme end of variability in the dose–concentration–response
relationship of a drug
. Not surprisingly, elderly frail individuals may display profound changes
in the pharmacokinetics and pharmacodynamics of a drug.
From Shah 2004 BJCP.
1.2.

Which patients should be targeted?
There are many different ways of identifying patients who might benefit from a targeted medication review, including by: • Counts of numbers of repeat drugs • Numbers of co-morbidities • Care home residence or being housebound • A combination of these
A key priority was to select patients in a way that was easily implementable across Scotland,
and for that reason it was decided to use iSPARRA version 3 data since mechanisms
already exist for data extraction and dissemination of identifiable lists. Other methods may
be equally feasible within particular Boards.
The Model of Care Group recommended targeting patients with 40-60% risk of emergency
hospital admission in the next 12 months who were also dispensed a large number of
different drugs in the previous year. would provide the greatest patient benefit for level 3
medication reviews; those in higher risk categories were deemed to be at higher risk of
admission due to other factors. those in higher risk categories were deemed of
less relevance since they will already be receiving a high level of management/monitoring.
The group recommends that Boards should prioritise patients on multiple medications, from
10 or more particular BNF sections, and/or high risk medicines. Reviews should start with
patients aged 75 years and over patients aged 65 to 75 years, as resources allow. Further
research is needed to determine which patients will realise greatest benefit.

Boards should identify the individual within the NHS Board to whom they would like
SPARRA lists based on the above criteria to be released. The confidential data release
form in see
since this is patient-identifiable data. For more detailed information on the derivation
of the above table and further data providing the numbers in other risk / BNF Section
.
Version 2 – controlled only when electronic – to be updated September 2013 Individuals within the July 2012 SPARRA Cohort1 with a risk score of 40-60% and dispensed items in 10 or more BNF sections2
Number with
Number with
Number with
Number with
Number of
Number in a
high risk
Number with
Number of
Number in a
high risk
Number with
NHS Board
high risk
high risk
care home4 medicines and
care home4 medicines and
in a care home
in a care home
Ayrshire and Arran Dumfries and Galloway Greater Glasgow and Clyde 1 SPARRA Version 3 estimates the risk of emergency admission in the next 12 months for approximately 3.2m individuals.
For the July 2012 release, this is the risk of emergency admission in the period 1st July 2012 to 30th June 2013.
2 The number of different BNF Sections in which an individual's dispensed items fall. Note that SPARRA Version 3 uses the most recent 12 months prescribing data available prior to the start of the risk year.
3 Defined as medications in any of the following BNF Sections: 2.1, 2.2, 2.4, 2.5, 2.8, 2.9, 4.1, 4.2, 4.3 and 10.1.
4 Identified by a CHI institution code of 93 or 98.
5 Evidence of Dementia has been determined either by Prescribing history (dispensed items within BNF Section 4.11) or previous inpatient admission to hospital where diagnosis at discharge includes ICD10 codes (F00-F03, F051); ICD9 (2900, 2901, 2902, 2904, 2908, 2909) Version 2 – controlled only when electronic – to be updated September 2013 Data collection and evaluation

Minimum data requirement for follow-up and evaluation.
NHS Boards will be asked to report back on the following data for both local and national
evaluation:
Number of patients reviewed from the list given and CHI numbers and date of

The national database of dispensed items held at ISD Scotland (New_PIS: the new
Prescribing Information System) will allow monitoring of pre-review dispensing patterns and
follow-up of post-review dispensing patterns.
Using the CHI identifier recorded at the point of review, the patient pathway can be traced
post-review. At a specified point in time after the review , which is yet to be confirmed, e.g.
one year, information about the patient admission history, the associated, pattern in GP
appointments or primary care contacts, outpatient attendance, A&E attendance, length of
stay , regular prescription at post-review date can be obtained.
For further details of the recommended data collection and evaluation, see

Reviewers can use the code " polypharmacy" in READ codes until a specific READ code
for "polypharmacy review" is established ( this may take up to 6 months) .
1.4.
Ongoing work and timescales

These can be summarised below:
Guidance document will be reviewed after 6 months for revisions form feedback and updated in September 2013 Development of iSPARRA to track changes in medication and potentially other health outcomes Development of indicators to understand risks and benefits of tackling polypharmacy. Analysis of Scotland wide data for polypharmacy Development of patient tools to help them actively take a role in polypharmacy reviews Development of tools for the clinicians undertaking polypharmacy reviews Version 2 – controlled only when electronic – to be updated September 2013 Section 2: Clinical Guidance
Version 2 – controlled only when electronic – to be updated September 2013 Drug review process
This review should be undertaken in the context of holistic care considering each medication and its impact on the individual clinical circumstances of each patient. As part of this it is important to consider the cumulative effects of medications. References / Further reading
CRITERIA / CONSIDERATIONS PROCESS/GUIDANCE
or Examples
Is there a valid and current
Identify medicine and check that it does have a valid and current e.g. PPIs- use minimum dose to control GI symptoms
indication? Is the dose
indication in this patient with reference to local formulary. Check the - risk of c.difficle and fracture dose is appropriate (over/under dosing?) e.g quinine use-
e.g. long term antibiotics
Is the medicine preventing rapid
Is the medicine important/essential in preventing rapid symptomatic e.g. Medications for Heart failure, medications for
symptomatic deterioration?
deterioration? If so, it should usually be continued or only be Parkinson's Disease are of high day to day benefit discontinued following specialist advice. and require specialist input if being altered. review of doses may be appropriate e.g. digoxin Is the medicine fulfilling an
If the medicine is serving a vital replacement function, it should e.g. thyroxine and other hormones
essential replacement function?
Consider medication safety
Strongly consider stopping Is the medicine causing:
-Any actual or potential ADRs?
Poorly tolerated in frail
Consider stopping a high risk combination " triple Whammy" -Any actual or potentially
patients? For guidance on
serious drug interactions?
Particular side effects?
May need to consider stopping Consider drug effectiveness in
For medicines not covered by steps 1 to 4 above, compare the this group/person?
medicine to the ‘Drug Effectiveness Summary' which aims to estimate effectiveness. Are the form of medicine and the Is the medicine in a form that the patient can take supplied in the
Consideration should be given to the stability of dosing schedule appropriate? Is
most appropriate way and the least burdensome dosing strategy? there a more cost effective
Is the patient prepared to take the medication? UKMI Guidance on Ensure changes are communicated to the patients' alternative with no detriment to
choosing medicines for patients unable to swallow solid oral dosage Pharmacist: Would this patient benefit form Chronic patient care?
forms should be followed. medication Service? Do you have the informed
Once all the medicines have been through steps 1 to 6, decide with
agreement of the
the patient/carer/or welfare proxies what medicines have an effect
patient/carer/welfare proxy?
of sufficient magnitude to consider continuation/discontinuation. Version 2 – controlled only when electronic – to be updated September 2013 Risk benefits of medication: ‘numbers needed to treat' and numbers
‘needed to harm'


The ‘number needed to treat' (NNT) is a measure used in assessing the effectiveness of a
particular medication, often in relation to a reduction in risk over a period of time. The NNT is
the average number of patients who require to be treated for one to benefit to be realised
compared with a control in a clinical trial. It is defined as the inverse of the absolute risk
reduction. So if treatment with a medicine for one year reduces the death rate over five years
from 5% to 1% (a very effective treatment), the absolute risk reduction is 4% (5 minus 1),
and the NNT is 100/4 =25.
In other words, the number needed to treat with that medicine for one year to prevent one
death is 25. The ideal NNT is 1 where everyone improves with treatment. The higher the
NNT, the less effective the treatment. There is always need to consider:
• What is the outcome being avoided? Death is more significant than a vertebral fracture, but different outcomes will be more or less significant to individual patients. • Over what period does the benefit accrue? Two drugs may have the same NNT to avoid one death, but the drug that achieves that over 6 months is more effective than the drug which takes 10 years to. You can put NNTs on the same timescale by multiplying or dividing the NNT appropriately, but there is an assumption that benefit accrues consistently over time (a not unreasonable assumption, but one that is difficult to test). • What are the TRUE costs of the drug? This will include monetary costs, but also costs associated with treatment burden, and harm/side effects. A medicine might save the life of one of the 25 people who take it, but if it led to all 25 suffering a debilitating side effect, its costs may outweigh its benefits.
NNTs are only estimates of average benefit, and it is rarely possible to know precisely what
the likely benefit will be in a particular patient.
The ‘uncertainty' in the number should be acknowledged since the construction of
confidence intervals around NNT does not generally give a valid interval.
‘Number needed to harm' (NNH) is a related measure which is the average number of
people exposed to a medication for one person to suffer an adverse event. Again, a defined
end point (e.g. GI bleeding or renal failure) requires to be specified and confounders may
require correction of the raw data i.e. in very elderly patients the risk of particular side effects
such as confusion and falls may be higher than on average . In discussion, the overall
benefit – risk ratio (NNT / NNH) requires to be ‘weighed' in the individual patient and may
vary considerably in people with polypharmacy depending on absolute risk, life expectancy
and vulnerability to adverse drug events.
Example:
The reference below illustrates that for benzodiazepines for night sedation NNT is 13 but the
NNH is 6
Glass, J. et al. Sedative hypnotics in older people with insomnia: a meta-analysis of risks
and benefits. BMJ 2005; 331: 1169

Version 2 – controlled only when electronic – to be updated September 2013 Numbers needed to treat drug effectiveness summary (see references for additional information)

ACE INHIBITORS

Indication
NNT per annum
To do what
Elevated Vascular Risk [Normal LV] Prevent one death [all causes] Trial ran for 5 years Impaired LV Function-mild/moderate Prevent one death [all causes] Likely symptomatic benefit Combination Therapy including ACE
ACE + Indapamide Prevent one stroke Trial ran for 5 years Secondary Prevention post MI > 80 yrs [ACE+ BB +ASP+ STAT] Prevent one Death ACE + Beta blocker for impaired LV Prevent one death Likely symptomatic benefit Impaired LV Mild /moderate ACE + BB Prevent one Death Likely symptomatic benefit Impaired LV Severe ACE + BB + Spiro Prevent one Death Likely symptomatic benefit ASPIRIN Primary Prevention
No longer recommended ASPIRIN Post Stroke/ TIA Prevent one stroke or MI or Vascular Death DYPYRIDAMOLE In addition to ASPIRIN post stroke/TIA
Prevent one vascular event BNF caution in cardiac disease CLOPIDOGREL post stroke or TIA
Dypridamole + Aspirin Prevent one vascular event ATRIAL FIBRILLATION
AF + another risk factor WARFARIN v ASPIRIN Prevent one Stroke- no difference in mortality AF (Secondary Prevention after Stroke) WARFARIN v ASPIRIN Prevent one stroke BP > 140/90 trial predominantly systolic Cardiovascular morbidity and mortality >80 yrs
Avoid one cardiovascular event 2 years for effect High Risk [Diabetes, vascular disease] Avoid one cardiovascular event 2 years for effect Cerebrovascular morbidity and mortality > 80 yrs
Avoid one cerebrovascular event 2 years for effect Cardiovascular morbidity and mortality > 60yrs
Avoid one cardiovascular event 4.5 years for effect High Risk [Diabetes, vascular disease] Avoid one cardiovascular event 4.5 years for effect HYPERTENSION (Tayside Day Hospital cohort)
Prevent one death NNT 30 if also Cardiovascular Disease NNT are a guide; they do not give exact figures for individuals patients Older people have increased absolute event rates, thus NNT to prevent one event may be lower in older people – conversely NNH are likely to be higher – see weighing the benefit / risk in NNT section 2.2 NNT per annum
To do what
Major Coronary Event. No difference in Mort to 5 years Post Stroke [Atrova 80 v Placebo] One Cardiovascular Event No difference in Mort to 5 years Tight HbA1c Control Strategies
Microvascular Risk ADVANCE [HbA1c7.3% v 6.5%] One microvascular event [predominantly retinal] Trial ran 5 years UKPDS [HbA1C 7.9% v 7%] One microvascular event [predominantly retinal] Trial ran 10 years Macrovascular Risk No difference at 10 years Metformin
Overweight /obese Diabetic One MI or Diabetes event or Death 10 year follow up Standard < 140 BP control in diabetes any means
One Stroke or major diabetes event or death 8 year follow up Tight BP control in diabetes
Prevent one stroke 4 years minimum for effect Number needed to harm for this strategy Osteoporosis [Alendronate + Calcium/VitD]
2y Prevention Vertebral #
2y Prevention Hip #
Notes for Osteoporosis
NNT per annum to prevent further # Potential symptomatic benefit re Vertebral # Normally 2 years needed to see effect.
High Risk Combinations
Warfarin
Drugs that are tolerated poorly in frail
STOP if dehydrated
These combinations are noted to be particularly + another antiplatelet. patients
Angiotensin 2 Receptor Blockers high risk and should be looked for and stopped It is particularly important to clarify if patients on at every drug review. NSAID
the following have a Valid and Current
+ACE or ARB + Diuretic [‘Triple Whammy' Indication and are still felt to be effective.
+azole antifungal Digoxin in higher doses 250 • Spironolactone Drugs for which specialist advice is strongly
• Antipsychotics In Dehydrated
+diagnosis heart failure advised before altering include:
• anticonvulsants for epilepsy Benzodiazipines particularly long term • antidepressant, antipsychotic and mood For example those suffering from more than +age >75 without PPI • Anticholinergics stabilising drugs (eg lithium) Phenothiazines [eg prochlorperazine] minor vomiting/diarrhoea. Restart when well (eg Heart Failure
• drugs for the management of Parkinson's Combinations painkillers [eg 24 to 48 hrs eating and drinking normally). +Glitazone +NSAID cocodamol v paracetamol] +Tricyclic antidepressant Adults with advanced heart failure can • disease-modifying antirheumatic drugs. decompensate rapidly off drugs and adults with more than minor dehydration in this group need urgent specialist advice. NNT are a guide; they do not give exact figures for individuals patients Older people have increased absolute event rates, thus NNT to prevent one event may be lower in older people – conversely NNH are likely to be higher – see weighing the benefit / risk in NNT section 2.2 Indications of shortened life expectancy

We suggest that following guidance contained in the prognostic indicators guidance from the
Gold Standards Framework incorporated into the ‘Living Well/ Dying Well' strategy enables
better identification of patients who may need supportive/ palliative care. A full copy of this is
available at:

Triggers which can be used to identify main patients include:
Where the answer to the question ‘would you be surprised if this person were to die in the next 6 to 12 months?' is ‘no'. Choice/ need – where a patient with advanced disease is making a choice for comfort care rather than ‘curative' treatment. One clinical indicator often associated is patients requiring help with multiple activities of daily living either at home or in care home due to: a. Advanced organ failure b. Multiple co-morbidity giving significant impairment in day to day function c. Advanced The Gold Standards Framework gives specific information as to what tends to indicate poor
prognosis in a number of conditions, for example frailty.
Frailty

Frailty is well defined as a ‘reduced ability to withstand illness without loss of function'.
The Gold Standards Framework defines this further as:
• Multiple co-morbidities with signs of impairment in day to day functioning • Combination of at least three of: o weakness o slow walking speed o low physical activity o weight Version 2 – controlled only when electronic – to be updated September 2013 medication
The following section outlines common medication issues. It includes advice on • high risk combinations to avoid • information on providing medication during intercurrent illness. • medicines which, if stopped, can result in rapid symptomatic decline and • medicines where specialist advice should be sought before changes are made.
Lists of medications considered not advisable in frail adults are available e.g. the STOPP
tool but these lists can be unwieldy to use in routine practice. The BNF sections to target is
a modified version of the STOPP tool developed in Tayside.

Medication most associated with admission due to adverse drug reaction
In a 2004 UK study the most common drug groups associated with admission due to
adverse drug reaction (‘ADR') were:
5. Antidepressants
Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820
patients M Pirmohamed et al, BMJ 2004;329:15-19
High risk drug combinations to avoid

The following are highlighted as being particularly high risk combinations and should be
avoided where possible and clearly justified when considered necessary. This list is NOT
exhaustive
, and the safety of other medication has to be considered depending on
individual circumstances. The list is supported by recent research looking at what
combinations are commonly found when analysing prescribing databases in Scotland.
NSAID
+ ACE inhibitor or A2RA + Diuretic + diagnosis heart failure + eGFR < 60 ml/min + age > 75 years without PPI • Heart Failure
+ Glitazone + NSAID + Tricyclic antidepressant
Warfarin
+ Other antiplatelet(s) Version 2 – controlled only when electronic – to be updated September 2013 +Azole antifungal High risk prescribing in primary care patients particularly vulnerable to adverse drug events: cross sectional
population database analysis in Scottish general practice. Guthrie B, McCowan C, Simpson CR, Dreischulte T,
Barnett K. BMJ 2011; 342:3514 doi: 10.1136/bmj.d3514
Drugs poorly tolerated in frail adults

• Digoxin in doses of 250 micrograms or greater • Antipsychotics • Benzodiazipines • Anticholinergics • Phenothiazines • Combinations
Anticipatory care during intercurrent illness: drugs and dehydration
Medicines to stop in dehydrated patients

For example, patients suffering from more than minor vomiting and/or diarrhoea:
• ACE inhibitors • Spironolactone or eplerenone
Restart when well (eg after 24 to 48 hours of eating and drinking normally). Adults with
advanced heart failure can decompensate rapidly and urgent specialist advice should be
sought.

Drugs that can be associated with rapid symptomatic decline if stopped

Drugs in this group may require review but commonly will require specialist advice or
cautious stepwise withdrawal:
• ACE inhibitors in heart failure (left ventricular impairment) • Diuretics in heart failure • Drugs for heart rate or rhythm control (beta-blockers; digoxin).
Drugs for which specialist advice is strongly advised before altering include:

• Anticonvulsants for epilepsy • Antidepressant, antipsychotic and mood stabilising drugs (eg lithium) • Drugs for the management of Parkinson's Disease • Disease-modifying antirheumatic drugs Version 2 – controlled only when electronic – to be updated September 2013 Areas for specific consideration

Combination Antiplatelet + Warfarin therapy

There are very few indications for the long term use of Warfarin with an antiplatelet drug. It is
however easy for a patient to end up on both if an indication for Warfarin develops while on
an antiplatelet drug. The bleeding risk of this combination is high.
Taking warfarin as baseline i.e. odds ratio of 1 risk of bleeding in a recent large study is as
follows
Aspirin
0.93 [0.88 to 0.98] 1.06 [0.87 to 1.29] Aspirin + Clopidogrel 1.66 [1.34 to 2.04] Warfarin + Aspirin 1.83 [1.72 to 1.96] Warfarin + Clopidogrel 3.08 [2.32 to 3.91] 13.9% bleed/patient year Warfarin + Aspirin + Clopidogrel 3.70 [2.89 to 4.76] 15.7% bleed/patient year
Bleeding defined as: admission to hospital with bleeding related episode or death with bleed.
Average Age in trial 70; data from 82 854 patients surviving hospitalisation with atrial
fibrillation. Stroke occurrence was lowest in warfarin only group.
[Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in
patients with atrial fibrillation Hansen ML, Sorensen R, Clausen MT, et al. Arch Intern Med.
2010 Sep 13;170 (16):1433-41.]

Management of blood glucose control - effects of intensifying control
The evidence from four key randomised controlled trials ( UKPDS 33, ACCORD, ADVANCE
and VAT shows that whilst intensive control can have benefits in reducing microvascular
events, there are also harms, in particular increase in hypoglycaemia ( increase 42 events
per 1000 treated patients over 4.4 years ( CI 25.8-61.7) ). The study from Currie et al
described below shows that optimal level of 7.5% was associated with lowest all cause
mortality.
Version 2 – controlled only when electronic – to be updated September 2013 Potential dangers in lower Hb A1Cs


Researchers analysed data from nearly 48,000 primary care patients who had stepped up
their hypoglycaemic treatment. Hb A1c around 7.5% had the lowest mortality. Risk of death
rose significantly on both sides of this reference group, reaching a hazard ratio of 1.52 (1.32
to 1.76) for patients in the bottom 10th of HbA1c concentration (median 6.4%), and 1.79
(1.56 to 2.06) for patients in the top 10th (median 10.5%).
The study does have limitations as it was an observational study and that hypoglycaemia
was not to be the only factor contributing to increase death in all patients, However, older
people were identified as being at greatest risk. These results are of particular concern for
the frailer groups of patients covered by the Polypharmacy Guideline who given the long
lead time to obtain any supposed benefits from low Hb A1c, may nonetheless suffer adverse
outcomes.
[Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study
The Lancet, 2010 Volume 375, Issue 9713, Pages 481-489C. Currie, et al.]
In addition patients who suffer from hypoglycaemia are at increase risk of falls

Newer oral hypoglycaemics and heart failure
Although the newer agents are effective at reducing HbA1c levels data are lacking to support
any reduction in microvascular or macrovascular events, especially concerning
cardiovascular effects and long term safety. For example, pioglitazone should not be used
in people with heart failure or a history of heart failure or those with a history of fractures
(especially postmenopausal), or bladder cancer. MHRA has therefore advised caution in
initiating and using such treatment in older people and advised that it should be reviewed
regularly .
There is a group of commonly prescribed effective drugs in which particular caution is
needed should an adult develop an intercurrent illness while taking them. For the duration of
Version 2 – controlled only when electronic – to be updated September 2013 illness (particularly if dehydrated and especially if also frail) the following advice should be
given. This applies to the duration of the illness and is separate from decisions relating to the
long term use of these drugs.

Anticholinergic effects of commonly prescribed medication.
Anticholinergics are well recognised as being problematic in frail adults. Predominantly the
concern has been around impaired cognition and falls risk. Recent research however also
points to a link to mortality increasing with the number and potency of anticholinergic agents
prescribed .
As well as the well known anticholinergic medication several commonly prescribed
medication that may not be thought of as anticholinergic have significant anticholinergic
effects.
The following table shows anticholinergic weighting of a number of common drugs. The
higher the number the stronger the effect.
The chart is intended to enlighten regarding
anticholinergic effects rather being used as a day to day tool.

Anticholinergic risk scale

a. Chlorpromazine b. Nortryptyline b. Amitryptyline d. Chlorpheniramine h. Prochlorperazine The Anticholinergic Risk Scale and Anticholinergic Adverse Effects in Older Persons. Rudolph JI et al Arch Intern Med. 2008;168(5):508-513 Results from further MRC study can be found on link below: Version 2 – controlled only when electronic – to be updated September 2013 Specific consideration for patients with dementia
Protocol for Review Flow-chart for the of Anti-dementia MedReview of Anti-Demen
A best practice guide for optimising treatment and care for behavioural and psychological
symptoms of dementia is available from Alzheimer's Society at:



Rationalisation of antipsychotics in patients with dementia - good practice guide for
deduction/ cessation of treatment

Patients who have dementia and who have been on antipsychotics for more than 3
months and have stable symptoms
should be reviewed with a view to reducing or
stopping antipsychotic medication. Antipsychotics are associated with an increased risk of
falls, delirium, cerebrovascular events and all-cause death
Priority groups for reducing antipsychotic medication include:
• People in care homes- the prescription of antipsychotics for BPSD is most common in these people, who are also more frail than other populations • People with vascular dementia- the risk of cerebrovascular events associated with antipsychotic medication may be higher in this population • People with dementia who also have a history of cardiovascular disease, cerebrovascular disease or vascular risk factors. The risk of cerebrovascular events associated with antipsychotic medication may be higher in this population
When not
to stop antipsychotic medication:
• Patients who have a co-morbid mental illness that is treated with antipsychotic medication, such as schizophrenia, persistent delusional disorder, psychotic depression or bipolar affective disorder should not have antipsychotic medication reduced without specialist advice.
Reduction of antipsychotics:

• As with initiation of medication, reduction should be carried out slowly with monitoring • Start with a reduction of 25% of the total daily dose. • If the current dose is low, e.g. at the suggested starting dose, the medication may be stopped without tapering the dose.
Review the effect
after one week to assess for:
• The re-emergence of the initial "target" symptoms • Discontinuation symptoms such as nausea, vomiting, anorexia, diarrhoea, rhinorrhoea, sweating, myalgia, paraesthesia, insomnia, restlessness, anxiety and agitation. These symptoms are more common with abrupt withdrawal of antipsychotic Version 2 – controlled only when electronic – to be updated September 2013 medication, and generally begin within 1 to 4 days of withdrawal and abate within 7 to 14 days. • If either of the above occurs the clinician should make an assessment of the risks and benefits of re-instating the previous dose of antipsychotic. Further attempts to reduce the antipsychotic should be made one month later with smaller decrements, for example 10% of the total daily dose. • If there are no particular problems after week 1 then the dose should remain the same with further review after week 4 (for risperidone and haloperidol) or fortnightly (for Quetiapine). • If the reduction has been tolerated without any of the effects described above then reduce by a further 25% and repeat the process. • There will be practical issues when reducing the dose, for example the availability and form of small doses of medication. It is recommended that this is discussed with a pharmacist. • It is suggested that once the total daily dose is reduced to the recommended starting dose for the individual antipsychotic, it may be stopped. Version 2 – controlled only when electronic – to be updated September 2013 BNF sections to target and other factors to consider when conducting a
review


Gastrointestinal system

• Proton pump inhibitors and H2 antagonists - consider reducing the dose or stopping, especially if antibiotics are required (remember increase in risk of C. difficile) . Consider co-prescribing of PPIs with clopidogrel. • Long-term laxatives- check compliance, check effectiveness- check dose and choice, check safety- reduce overuse of laxatives if possible. Advice regarding non-pharmacological management is available on
Cardiovascular system in general


• Anticoagulants - do patients on anticoagulants have an active indication for anticoagulant therapy? Is monitoring robust? Is the INR within the recommended therapeutic range? Are there frequent falls (>1 per week)? • Antiplatelets- does the patient have a history of coronary, cerebral or peripheral symptoms/ events?- If not – consider stopping antiplatelets. Ensure aspirin/clopidogrel combination reviewed as per cardiology advice. Reduce aspirin to evidence-based doses. • Diuretics for dependent ankle oedema - consider alternative ways of managing oedema, consider medication causes e.g. calcium channel blockers • Digoxin in the presence of CKD - consider reducing the dose, or stopping • AF - is the patient prescribed warfarin or aspirin (use beta blocker, digoxin or amiodarone as a marker of AF). • Review long-term quinine use- see MHRA advice • Angina - is the patient prescribed aspirin (use beta blocker, or long-acting nitrates or calcium channel blocker as a marker of angina) • Consider reducing anti-anginal medication particularly if mobility has decreased with less need for medication Some guidance on NNT for various indications can be found in
Central nervous system and psychotropic medication

• Hypnotics and anxiolytics - discuss reducing long-term therapy with the aim of • Antipsychotics for BPSD (Behavioural and Psychological Symptoms of Dementia). in dementia - review the continued need, consider reducing the dose or stopping in line with local guidance • Cognitive enhancers - Is the cognitive enhancer still effective/ tolerated - What is the most recent MMSE? Contact specialist services for advice. • Review combinations of antidepressants such as tricyclic antidepressants for analgesia used in combination with other antidepressants for depression • In general SSRIs are better tolerated in people with dementia who also have depression • Metoclopramide - review long-term use • Antihistamines for vertigo - review long-term use • Consider cumulative GI effects when co-prescribing SSRI's+NSAID's/ aspirin Version 2 – controlled only when electronic – to be updated September 2013 Analgesic medication

• Long term use of strong opioids for mild-moderate pain – review diagnosis (is pain neuropathic or otherwise not responsive to opiates) and effectiveness - discuss stepping down therapy • Consider non-pharmacological treatment such as gentle exercise, relaxation or • Consider topical agents • Check compliance with long-term analgesia • Check effectiveness- step up or step down analgesia using the WHO analgesic ladder available on • for non malignant pain see Fife guidance • Check safety - reduce use of NSAIDs and opioids and amitriptyline if possible. Prescribe laxatives with opioids. • Check labelling includes minimum interval between doses and maximum dose/ • Reduce likelihood of paracetamol overdose from concurrent use of more than one paracetamol product. • Consider paracetamol dose reduction where low body weight or significant reduction in renal or hepatic function Endocrine system

• Metformin – use with caution in renal impairment and avoid if eGFR < 30ml/min • Oral corticosteroids for long term use – maintenance dose should be kept as low as possible with withdrawal considered where feasible. When possible local treatments e.g. inhalations, creams etc should be used in preference to systemic treatment

Urogenital system

• Alpha-blockers for more than 2 months for benign prostatic hypertrophy in men with long term urinary catheters - consider stopping • Finasteride in men with long term urinary catheters- discuss with urology team re:
Musculoskeletal system

• NSAIDs - is the patient on a long-term NSAID for non-inflammatory pain - discuss • Bone health - has the risk of osteoporosis been assessed? Can the patient take bisphosphonates or calcium as prescribed? Consider local guidelines around management of osteoporosis and bisphosphonate holidays • DMARD - does the patient have moderate-severe rheumatoid disease lasting for >12 weeks. Consider referral to rheumatology Version 2 – controlled only when electronic – to be updated September 2013 • Review the need for long-term antibiotic prophylaxis- • Review the need for long term antibiotic/ antifungal/ steroid creams and
Cost effective prescribing
Refer to the full range of local prescribing indicators to support cost effective prescribing.
Consider issues such as :
• Can dose schedules be optimised e.g. use higher strength formulations of pregabalin, quetiapine or lower strength formulations of gabapentin 600/800mg tablets and fluoxetine 60mg caps • Are any drugs of limited value being prescribed e.g. naftidrofuryl, quinine - review • Are any non formulary medicines prescribed – review • Therapeutic duplication- are two drugs from the same class prescribed? e.g. Lactulose and Laxido- stop one and titrate the dose of the other. • "As required" medicines that are on repeat but not needed (e.g. Paracetamol) • Other prescribed items which are no longer needed e.g. Test strips due to change in advice regarding frequency of monitoring blood glucose in type II diabetes.
Prescribing for symptoms or in particular conditions

Falls

Review the need for:
• Any long-acting or long-term hypnotic or anxiolytic. It is useful to reduce the dose if the
medication cannot be stopped completely. Specific information on the reduction of benzodiazepines and Z drugs can be found as a NHS Clinical Knowledge Summary, and insomnia guidance at • Antihypertensives/diuretics. Stopping or reducing the dose of Calcium Channel Blockers may be indicated if the patient has ankle swelling resistant to diuretics. For people on combinations of antihypertensives, consider reducing the doses or stopping some of the drugs if signs of postural hypotension are evident. If diuretics are for dependent ankle oedema consider other management strategies. Optimise antihypertensive therapy bearing in mind the falls risk, mobility and postural hypotension. • Other CNS medication- review the need for antidepressants and antipsychotics, and anti-epileptic medication especially if used for atypical pain • First generation (sedating) antihistamines • Review any anticholinergic drugs for bladder spasm or other drugs with anticholinergic side effects e.g. tricyclic antidepressants, digoxin. Version 2 – controlled only when electronic – to be updated September 2013 2.9 References

Trials used to complete drug effectiveness summary

Cardiac trials

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and
congestive heart failure. The SOLVD Investigators NEJM Volume 325:293-302 August 1,
1991 Number 5
HOPE Study N Engl J Med 2000;342;145–153
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999 Jan
2;353(9146):9-13.
The Randomized Aldactone Evaluation Study Investigators. The Effect of Spironolactone on
Morbidity and Mortality in Patients with Severe Heart Failure [RALES] Bertram Pitt, M.D.,
Faiez Zannad, M.D., Willem J. Remme, M.D., Robert Cody, M.D., Alain Castaigne, M.D.,
Alfonso Perez, M.D., Jolie Palensky, M.S., Janet Wittes, Ph.D. NEJM Volume 341:709-717
September 2, 1999 Number 10
Setoguchi et cal Improvements in Long Term Mortality after Myocardial Infarction J of AM
College of Cardiology Vol. 51, No. 13, 2008 April

Stroke secondary prevention

Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of
antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk
patients. BMJ 2002;324:71–86.

PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure-
lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack.
Lancet 2001;358:1033–1041.

10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes Rury R Holman, Sanjoy
K Paul, M Angelyn Bethel, David R Matthews, H Andrew W Neil. The New England Journal
of Medicine. Boston: Oct 9, 2008. Vol. 359, Iss. 15; pg. 1577
Halkes et al Dipyridamole plus aspirin versus aspirin alone in secondary prevention after TIA
or stroke: a metaanalysis by risk J. Neurol. Neurosurg. Psychiatry 2008;79;1218-1223
Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary
prevention of stroke and other vascular events. A systematic review. Stroke
2003;34:2741–2749.
High-Dose Atorvastatin after Stroke or Transient Ischemic Attack The Stroke Prevention by
Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators NEJM Volume
355:549-559 August 10, 2006 Number 6
NICE technology appraisal guidance 210 Clopidogrel and modified-release dipyridamole for
the prevention of occlusive vascular events (review of technology appraisal guidance 90)
Dec 2010
Version 2 – controlled only when electronic – to be updated September 2013 Warfarin

Warfarin versus aspirin for stroke prevention in an elderly community population with atrial
fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a
randomised controlled trial Lancet 2007; 370: 493–503.
Hypertension

Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic
Reviews
2009, Musini VM, Tejani AM, Bassett K, Wright JM Issue 4. Art. No.: CD000028.
DOI: 10.1002/14651858.CD000028.pub2.
Statins

Effects Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol
lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin
Survival Study (4S). Lancet 1994;344:1383-1389.
LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis
of randomized controlled trials. JAMA. 1999;282:2340-2346.
Goldberg RB, Mellies MJ, Sacks FM, Moye LA, Howard BV, Howard WJ, Davis BR, Cole
TG, Pfeffer MA, Braunwald E. Cardiovascular events and their reduction with pravastatin in
diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol
levels: subgroup analyses in the Cholesterol and Recurrent Events (CARE) trial. Circulation
1998;98:2513-2519.
West of Scotland Coronary Prevention Group. West of Scotland Coronary Prevention Study:
identification of high-risk groups and comparison with other cardiovascular intervention trials.
Lancet 1996; 348: 1339-1342.
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the
Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-
controlled trial. Lancet. 2004 Aug 21-27;364(9435):685-96 of intensive glucose lowering in
type 2 diabetes Gerstein HC, Miller ME, Byington RP, et al. N Engl J Med. 2008 Jun
12;358(24):2545-59.
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk
individuals: a randomised placebo controlled trial Heart Protection Study Collaborative
Group THE LANCET • Vol 360 • July 6, 2002.

Diabetes

Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study
The Lancet, 2010 Volume 375, Issue 9713, Pages 481-489C. Currie, et al.
Effect of intensive control of glucose on cardiovascular outcomes and death in patients with
diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 2009; 373: 1765–
72 K Ray et al.
Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes
The ADVANCE Collaborative Group N Engl J Med 2008;358:2560–2572.
Version 2 – controlled only when electronic – to be updated September 2013
Effect of intensive control of glucose on cardiovascular outcomes and death in patients with
diabetes mellitus: a meta-analysis of randomised controlled trials Kausik K Ray, Sreenivasa

Rao Kondapally Seshasai, Shanelle Wijesuriy, Rupa Sivakumaran, Sarah Nethercott, David
Preiss, Sebhat Erqou, Lancet 2009; 373: 1765–72.
Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus The ACCORD Study
Group (10.1056/NEJMoa1001286) was published on March 14, 2010, at NEJM.org.

Osteoporosis

Alendronate for the primary and secondary prevention of osteoporotic fractures in
postmenopausal women. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V,
Coyle D, Tugwell P. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.:
CD001155. DOI: 10.1002/14651858.CD001155.pub2.
Renal

Randomised placebo- controlled trila of effect of ramipril in decline in glomerular filtration
rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy [REIN study].
The Gisen Group Lancet 1197;349:1857-63.
Renal Function and requirement for dialysis in chronic nephropathy patients on long term
ramipril: REIN follow-up trial. Gisen Group Lancet 1998;352:1252-56.
Effects of inhibitors of the renin-angiotensin system and other antihypertensive drugs on
renal outcomes:systematic reviews and meta-analysis. Casas J, Chua W et al Lancet
2005;366:2026-33.
Bleeding risk and antiplatelet strategies

Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in
patients with atrial fibrillation Hansen ML, Sorensen R, Clausen MT, et al. Arch Intern Med.
2010 Sep 13;170 (16):1433-41.
Aspirin in secondary prevention

Discontinuation of low dose aspirin and risk of myocardial infarction: case control study in
UK primary care. Rodriguez LA, Cea-Soriano L, Martin- Merino E, Johansson S. BMJ 2011;
343:d 4065.
Other

Older Patients With Multiple Comorbid Diseases: Clinical Practice Guidelines and Quality of
Care Cynthia M. Boyd; Jonathan Darer; Chad Boult; et al. JAMA. 2005;294(6):716-724.
High Risk Prescribing in primary care patients particularly vulnerable to adverse drug events:
cross sectional population database analysis in Scottish general practice. Guthrie B,
McCowan C, Simpson CR, Dreischulte T, Barnett K. BMJ 2011; 342:3514 doi:
10.1136/bmj.d3514 Source of high risk drug group information.
Version 2 – controlled only when electronic – to be updated September 2013 Section 3: Administrative Considerations
Version 2 – controlled only when electronic – to be updated September 2013 What should be happening under QOF to address medication reviews?

As part of the GP contract, medication review is covered under medicines indicator 11 and
12- detail is shown below:

Medicines 11
A medication review is recorded in the notes in the preceding 15 months for
all patients being prescribed four or more repeat medicines (Standard 80%)
Medicines 12 A medication review is recorded in the notes in the preceding 15 months for
all patients being prescribed repeat medicines (Standard 80%)
The detailed guidance states:
Medicines 11.1 practice guidance

Medication is by far the most common form of medical intervention. Four out of five people
aged over 75 years take a prescription medicine and 36 per cent are taking four or more.
However, we also know that up to 50 per cent of medicines are not taken as prescribed,
many medicines in common use can cause problems and that adverse reactions to
medicines are implicated in 5 - 17 per cent of hospital admissions.
Involving patients in prescribing decisions and supporting them in taking their medicines is a
key part of improving patient safety, health outcomes and satisfaction with care. Medication
review is increasingly recognised as a cornerstone of medicines management. It is expected
that at least a Level 2 medication review will occur, as described in the briefing paper linked
below:

The underlying principles of any medication review, whether using the patient's full
notes or face to face are:

1. All patients should have the chance to raise questions and highlight problems about 2. Medication review seeks to improve or optimise impact of treatment for an individual 3. The review is undertaken in a systematic way by a competent person 4. Any changes resulting from the review are agreed with the patient 5. The review is documented in the patient's notes 6. The impact of any change is monitored
Guidance is given in the document as to how this might be evaluated
Please see the below link to QOF guidance 2012/13

Version 2 – controlled only when electronic – to be updated September 2013 SPARRA data for all risk categories and authority for access to data
Polypharmacy analysis

Polypharmacy-July 20

SPARRA (Scottish Patients at Risk of Readmission and Admission) is a risk prediction tool
developed by ISD which predicts an individual's risk of being admitted to hospital as an
emergency inpatient within the next twelve months. Each quarter, risk scores are calculated
for approximately 3.2 million individuals aged 16 and over (approximately 62% of the
Scottish population) and details of those whose score indicates that they may be at
increased risk of emergency hospital admission are distributed to NHS Boards, CHPs and
other health agencies.
The SPARRA risk score is the percentage likelihood that the individual will have an
emergency hospital admission in the next twelve months. The current SPARRA algorithm,
SPARRA Version 3, calculates the risk of admission using a statistical model based on each
individual's history of hospital admission, A&E attendance, outpatient attendance and
psychiatric inpatient admission. The model also takes account of the medication dispensed
to an individual in the most recent 12 months of data available. For further details please
see: .
This analysis makes use of data from the January 2012 SPARRA release to look at the
number of older adults in each NHS Board area in various risk score and polypharmacy
categories. The purpose of the analysis is to provide data to support the decision regarding
which group of patients to target for medications review.
SPARRA Risk Score: The risk scores presented relate to the estimated risk of emergency
hospital admission for the period 1st July 2012 to 30th June 2013. Patients have been
grouped by risk scores into 20-40%, 40-60% and 60-80% - i.e. low to moderate, moderate
and high risk of emergency admission.
Polypharmacy: The polypharmacy measure used in this analysis is the number of different
BNF Sections dispensed to each individual in the twelve month period from 1st June 2011 to
31st May 2012. Figures are presented for 5-9 and 10+ BNF Sections.
Age: Age as at 1st July 2012. Figures are presented for individuals aged 65 and over and for
those aged 75 and over.
The tables show the number of individuals in each NHS Board area who are in each of the
above risk score, polypharmacy and age categories. The numbers taking high risk
medications, who are in a care home and who have prescriptions and/or previous hospital
admissions which indicate dementia are also shown. High risk medications are defined as
medications in any of the following BNF Sections:
2.1 – Positive inotropic medication
2.2 – Diuretics
2.4 – Beta-adrenoceptor blocking medication (beta-blockers)
2.5 – Hypertension and heart-failure
2.8 – Anticoagulants and protamine
2.9 – Antiplatelets
4.1 – Hypnotics and anxiolytics
Version 2 – controlled only when electronic – to be updated September 2013 4.2 – Medication used in psychoses and related (Antipsychotics) 4.3 – Antidepressants 10.1 – Medication used in rheumatic diseases and gout Please note that cells with small values have been suppressed to avoid the risk of disclosure. It is proposed that a sensible target group for medications review might be individuals with a 40-60% risk of admission - i.e. older patients with high levels of polypharmacy and moderate risk of admission. The rationale for this is that individuals in the lower risk strata (20-40%) taking multiple medications are likely to be relatively stable in their condition and those in the higher risk group (60-80%) may already be receiving a high level of management/support. Examination of the analysis will allow this group of patients to be broken down further with a view to identifying selection criteria which balances numbers of patients and the likely benefit to these patients of medications review. For example there are just over 35,000 individuals in the age 75+, 40-60% risk and 10+ BNF sections category. This equates to approximately 35 patients who would be eligible for review in an average practice. The analysis also shows that 98% of individuals in this category are taking one or more high risk medications, 19% are in a care home and 15% have prescriptions and/or previous hospital admissions which indicate dementia. Reducing the age threshold to 65 increases the average number of patients per practice to 44. SPARRA Confidential SPARRA Reporting Data Release Form (P Version 2 – controlled only when electronic – to be updated September 2013 Searches for GP prescribing systems: VISION and EMIS
How to Find Patients Polypharmacy.VisSrc Polypharmacy Search for Polypharmacy ES Thanks to Oliver Campbell and Barry Melia, NHS Lothian for VISION searches and to NHS Borders for EMIS searches. Version 2 – controlled only when electronic – to be updated September 2013 Data and evaluation

Minimum data requirement for follow-up and evaluation.
NHS Boards will be asked to report back on the following data for both local and national
evaluation:
Number of patients reviewed from the list given and CHI numbers and date of

The national database of dispensed items held at ISD Scotland (New_PIS: the new
Prescribing Information System) will allow monitoring of pre-review dispensing patterns and
follow-up of post-review dispensing patterns.
Such monitoring and follow-up of dispensing at patient level depends upon CHI number
being present in New_PIS for a sufficient proportion of dispensed items. CHI completeness
on New_PIS is currently running at around 95% overall and is slightly higher than this for
prescriptions issued within GP surgeries. Thus dispensing histories can be assessed with a
reasonable level of accuracy.
Post review – data collection

Using the CHI identifier recorded at the point of review, the patient pathway can be traced
post-review. At a specified point in time after the review , which is yet to be confirmed, e.g.
one year, information about the patient admission history, e.g. length of stay , regular
prescription at post-review date can be obtained.
Thus if we know the CHI number and date of each review, we will be able to ascertain in
whatever detail is necessary, the level and pattern of dispensing for each patient in a given
period before and after the review. This will enable evaluation of the impact of the reviews in
terms of, for example, number of items dispensed, specific items dispensed and cost.
To assist implementation of the guidance, work will continue to develop GP IT templates for
VISION and EMIS , that will assist clinicians follow the drug review process within their
consultations. An example of such a template is shown in
If boards want to collect more detailed data, then the collectiomay be useful for this purpose.

Recommended method of evaluation

Given the data and information that is likely to be available at the point of review, the most
feasible form of health economic evaluation would be a cost consequence analysis (CCA).
This is a form of cost effectiveness analysis comparing alternative interventions or
alternative states in which the components of incremental costs (e.g., pharmaceutical
reviews, hospitalisation) and consequences (e.g., health outcomes, adverse effects) are
converted into a cost-effectiveness ratio.
Version 2 – controlled only when electronic – to be updated September 2013 In the case of polypharmacy reviews CCA would measure the direct (and indirect) costs
associated with the intervention, recording physical changes that happen directly and
indirectly after intervention.
This method was selected because it avoids issues associated with sample selection,
including sample selection bias, ethical difficulties with dividing the patient sample into
review/non-review and regression to the mean, which would complicate this type of analysis.

Preliminary estimates of direct cost avoidance from medications stopped

The following table gives a potential overview of the scale and range of potential costs
avoided
(potential savings) from stopping medications as a consequence of a scheduled
review. These estimates are purely for illustrative purposes and are not to be seen as set
target against which outcomes should be measured.
The table makes use of estimates of the number high risk patients which fall into the relevant
SPARRA selection criteria. Note that the age group 65+ includes the group of 75+ patients,
however, the two segments of 5-9 BNF and 10+ BNF sections are independent.
In the event that one or two items are stopped per review respectively and applying an
average cost per item of £10.93 (BNF 2010/11 published statistics), this would gives a range
of one-off cost avoided of between roughly £72k and £944k respectively. If it is assumed
that each of these items can be stopped on an ongoing babsis, then annual costs reduction
over one year (average of 6 prescriptions), would be between approximately £433k and
£5.66m

Version 2 – controlled only when electronic – to be updated September 2013 Estimated cost avoidance from medications stopped through polypharmacy review
10+ BNF sections
5-9 BNF sections
Number of patients1 with high risk 34,454 43,190 6,610 7,832 medicines2
Average cost per item from BNF £10.93 £10.93 £10.93 Assumed cost avoidance if 1 item £376,422 £471,866 £72,217 £85,567 Assumed cost avoidance if 2 items £752,845 £943,733 £144,433 Assumed number of repeats stopped per item over one year Assumed cost avoidance if 1 item £433,300 £513,405 stopped repeatedly for one year Assumed cost avoidance if 2 items £866,600 £1,026,809 stopped repeatedly for one year 1Individuals within the January 2012 SPARRA Cohort1 with a risk score of 40-60% and dispensed items in 10 or more BNF sections, age 65+ category includes age 75+ category 2 Defined as medications in any of the following BNF Sections: 2.1, 2.2, 2.4, 2.5, 2.8, 2.9, 4.1, 4.2, 4.3 and 10.1.
It is to note, however, that these estimates do not take into consideration the indirect costs
avoided
(indirect savings) through wider changes in the patients' pathway, the costs of
implementing the
review, and most importantly, a monetisation of the wider health
benefits
received by the patients, as outlined above.
Version 2 – controlled only when electronic – to be updated September 2013 Data collection tools

Quantitative
Polypharmacy review template
scotland.gov.uk dc2 FS6_Home Z6039

Qualitative
Post review questionnaire, thanks to Rhona Gould, NHS Tayside
questionnaire May 20
VISION/ EMIS systems template

template v3.0.doc

National therapeutic indicators- currently available
Currently national therapeutic indicators have been developed and three of these currently
focus on areas highlighted under polypharmacy.


There are other areas that may be developed in the future:
• Antimuscarinic medication for urinary infrequency • Polypharmacy Version 2 – controlled only when electronic – to be updated September 2013 Key learning from models of care that have been used in Scotland

NHS Highland

Reviews were carried out in GP practices with support from primary care pharmacists and
Geriatrician.
Preliminary ESCRO data to the end of March 2011 (approximately six months into project)
for North, Mid and South East Highland CHPs have demonstrated that 3,836 patients
(1.83% of all patients) were placed on polypharmacy registers in GP practices. Of these
patients:
• 3,741 (98%) received a polypharmacy medication review • 859 (20%) were resident in a care home • 1,748 (46%) had an anticipatory care patient alert (ACPA) • 1,078 (25%) had at least one medicine stopped (the total number of medicines stopped was 2289) • The majority of patients therefore had no medications stopped • Patients who had medication stopped had an average of 2.5 medications stopped • 365 (8%) had at least one drug modified or changed (the total number of medicines modified or changed was 490) The reasons for medication review being conducted were as follows: Count (more than one reason
may have applied to individual
patients)

Patient on > 10 prescribed items and needs number of medicines reviewed Patient has suffered a side effect of medication Patient has an indication of shortened life
expectancy
Guidelines indicate need for Polypharmacy

The medicines most commonly stopped were medicines that are most commonly
prescribed. Most of these are low cost medicines.
Estimated Approx £5.50 per drug per
month saved. Cost of reviews as to March 2011. [£60 per review * 3741 = £224 460; £5.50
for each drug stopped for a year = £151, 000]
22.1% drugs stopped in Chapter 4 BNF (e.g. analgesics, hypnotics, antidepressants, etc)
however, drugs were stopped across a huge range. The top 13 stopped (50% of drugs
stopped are in this group). The other 50% are across 140 different BNF codes. Creams,
dressings, etc excluded.
Version 2 – controlled only when electronic – to be updated September 2013 Cholesterol lowering Osmotic Laxatives Opiod Analgesics Oral Anticoagulants
The figures for drugs stopped is felt to be an underestimate. There were software
difficulties in that if a GP removed drugs from a repeat prescribing list as part of a
review then went back to fill in the data on drugs stopped for the Enhanced Service
payment at a later date.
Relationship to QOF

In order to avoid concerns over an increase in QOF exemptions it was agreed across
Highland that if a QOF indicated drug was stopped as part of a Polypharmacy review
following the NHS Highland Guideline that the exemption would be coded as
‘Polypharmacy'. This allowed uniform coding across Highland.

National Level Data

ISD has been involved in trying to track any changes in prescribing patterns across NHS
Highland in older adults following the guidelines introduction. At present there seems to be a
flattening of the increase (and a small dip in some age groups) versus a previous trend of
steady in crease in the number of adults on > 10 medications.
To be useful this data will need to be compared to national trends.
Version 2 – controlled only when electronic – to be updated September 2013 NHS Tayside

Various models of care have been tested in Tayside. All of these involved face-to-face level
3 medication reviews with the patient (and carer/ welfare proxy where appropriate)
Models included reviews by:
• GP as a single professional • Locality (practice) pharmacist as a single professional • Medicine for the elderly consultant with specialist pharmacist • GP with locality pharmacist and a medicine for the elderly consultant Patients reviewed depended on the model used and the remuneration available, and groups targeted included: • Those in care homes • Those over 75 years old on more than 6 medicines and with a long term condition • Those over 75 years old on more than 12 medicines
Outcomes

Quantitative and qualitative data were collected. One of the main aims of the workstream
was to involve GP practices in some model of polypharmacy medication review. After 1 year
more than 50% of GP practices had participated in at least one project. The multidisciplinary
model (GP with pharmacist and medicine for the elderly consultant) with access to both
primary care and secondary care medical records resulted in more changes to medication
than a single professional model. Patients were generally positive about the reviews:
Patient quote after review: "its revolutionised my breathing".
Number of medication changes – comparison of single profession vs MDT
Single prof (n=86) increased Total meds 2.19 1.28 <0.001 decreased Total changes NB. Means given, although significant skew. Medians for most groups = 0 Version 2 – controlled only when electronic – to be updated September 2013 Relationship of number of changes to number of medications prescribed:
R=0.16, p for trend: <0.001 R=0.37, p for trend: <0.001 Version 2 – controlled only when electronic – to be updated September 2013 Key learning

Some of the staff learning from the multidisciplinary model includes:
• Paper reviews are not as good as having the patient/ carer present. e.g. for housebound patients we may do a paper review but we can't ask questions about analgesia, or when they take medicines • The combined review is much more effective that an individual doing a review • Quality improvements- we are picking up people who have fallen through the net and • Primary care (GP and pharmacist) have learned from the consultant and vice versa Version 2 – controlled only when electronic – to be updated September 2013 NHS Lothian

In Lothian all GP practices were invited to take part in polypharmacy reviews. The practices
were asked to link the reviews with patient Anticipatory Care Plans (ACP's) and can be
categorised into two arms:
• Practices were asked to review all patients resident in nursing homes • Review patients living in the community, aged 75 years and over and taking 10 or
Lead practices for each nursing home in Lothian were identified through the primary care
contracts team and VISION/ EMIS searches developed which practices were asked to run in
order to identify appropriate community patients for review. The reviews were jointly
undertaken with clinical pharmacists and the GP after initial preparation by the pharmacist. A
geriatrician was available for the reviews if the GP wanted additional support either face to
face, telephone or email.
Regular peer review amongst clinical pharmacists occurred and geriatricians attended to
speak about decision making for specific drug groups e.g. dementia therapies.
Clinical guidelines shared with all practices, and used at the joint reviews had been peer
reviewed by local consultants, specialist pharmacists, GP leads and approved for use
through the appropriate medicines governance committees of Lothian.

Initial findings from the pilot study

There were 69 GP practices participating in the pilot project from January 2012 – end April
2012. Reviews are ongoing and as at end June 2012 pharmacists have undertaken or are in
progress of completing over 1290 patient reviews (of these 829 patients were resident in
nursing homes and 461 resident in the community).
Detailed analysis of GP returns following implementation of the agreed prescribing actions
has been undertaken on 186 patients – analysis continues on an ongoing basis for all other
patients.
The number of medicines stopped were:
Of which 33% were high risk medicines The number of medicines reduced were: Of which 48% were high risk medicines Examples of high risk medicines stopped were as follows (expressed as a percentage of all
high risk medicines stopped (n=44)
Aspirin / clopidogrel
Antidepressant / Anxiolytics Anticholinergics
Examples of high risk medicines with doses reduced were as follows (expressed as a
percentage of all high risk medicines reduced (n=14)
Version 2 – controlled only when electronic – to be updated September 2013 Antidepressants / Anxiolytics Anticholinergics
A primary care pharmacy technician undertook detailed analysis of medicines stopped and
reduced. The financial efficiency saving from the holistic level 3 medication review
demonstrated an average saving of £135 per annum per patient reviewed by the clinical
pharmacist and GP.

In addition an identified £10.6K of annual cost avoidance was identified from the 186
analysed reviews and accounts for duplicate prescriptions, identified over ordering and
inactive repeats / as required medications.

NHS Forth Valley
In Forth Valley as part of their QOF QP programme practices were asked to review 4
patients per 1000 as per NHS Highland guidance. Results are shown below:
Forth Valley
Total Patients Reviewed: Total Meds Stopped: Total Meds Restarted: Version 2 – controlled only when electronic – to be updated September 2013 67 ADR/not tolerated
2 Recurrence of Symptoms/Signs
145 ADR/not tolerated
19 Recurrence of Symptoms/Signs
Patient felt unwell
Patient felt unwell
No Longer Indicated
Patient wished to restart
No Longer Indicated
Patient wished to restart
In High Risk Combination
In High Risk Combination
10 ADR/not tolerated
0 Recurrence of Symptoms/Signs
85 ADR/not tolerated
5 Recurrence of Symptoms/Signs
Patient felt unwell
Patient felt unwell
No Longer Indicated
Patient wished to restart
No Longer Indicated
Patient wished to restart
In High Risk Combination
In High Risk Combination
115 ADR/not tolerated
16 Recurrence of Symptoms/Signs
42 ADR/not tolerated
1 Recurrence of Symptoms/Signs
Patient felt unwell
Patient felt unwell
No Longer Indicated
Patient wished to restart
No Longer Indicated
Patient wished to restart
In High Risk Combination
In High Risk Combination
81 ADR/not tolerated
8 Recurrence of Symptoms/Signs
224 ADR/not tolerated
10 Recurrence of Symptoms/Signs
Patient felt unwell
Patient felt unwell
No Longer Indicated
Patient wished to restart
No Longer Indicated
Patient wished to restart
In High Risk Combination
In High Risk Combination
61 ADR/not tolerated
4 Recurrence of Symptoms/Signs
626 ADR/not tolerated
28 Recurrence of Symptoms/Signs
Patient felt unwell
Patient felt unwell
No Longer Indicated
Patient wished to restart
No Longer Indicated
Patient wished to restart
In High Risk Combination
In High Risk Combination
Version 2 – controlled only when electronic – to be updated September 2013 Polypharmacy Short Life Working Group membership


Henry Simmons
Patient Representative, Alzheimer's Scotland National Clinical Lead, Healthcare Improvement Scotland Clinical Lead, SPSP, Healthcare Improvement Scotland Information Consultant, ISD, NHS National Services Scotland Principal Information Analyst, ISD, NHS National Services Scotland Nancy Grieg Patient Representative Liaison, LTCAS Patient Representative, LTCAS Pharmacist, NHS Ayrshire and Arran Director of Pharmacy, NHS Education for Scotland GP, NHS Education for Scotland Practice Nurse, NHS Education for Scotland Lead for Prescribing and Clinical Pharmacy, NHS Greater Associate Medical Director, NHS Fife Director of Pharmacy, NHS Fife Consultant Geriatrician, NHS Greater Glasgow and Clyde Programme Manager, Health Improvement Scotland Consultant Geriatrician, NHS Highland CHP Pharmacist, NHS Highland Director of Pharmacy, NHS Highland GP Lead Self Management and Health Literacy, Scottish Palliative Care Consultant, NHS Lothian Staff Side, NHS Lothian eHealth, NHS Lothian/ Scottish Government Lead Clinical Pharmacist (Elderly), NHS Tayside Associate Medical Director, NHS Tayside Professor in Primary Care, University of Dundee Senior Lecturer in Ageing and Health, University of Dundee Vice Chair, RCGP Community Pharmacist, Romanes Pharmacy Anna Marie McGregor Professional Support Pharmacist, RPS Alpana Mair (Chair) Prescribing Advisor/ Therapeutic Partnership Lead Scottish Government Sheena Macdonald GP Lead, Scottish Government Health Economist, Scottish Government Gregor Smith (Chair) Associate Medical Director, NHS Lanarkshire Programme Director, Better Together, Scottish Government Programme Manager, QuEST, Scottish Government Improvement Advisor, QuEST, Scottish Government Version 2 – controlled only when electronic – to be updated September 2013

Source: http://www.gpled.co.uk/GP_LED/avoidable_emergency_admissions_files/Polypharmacy%20full%20guidance%20v2.pdf

Functional expression of a proton-coupled organic cation (h+/oc) antiporter in human brain capillary endothelial cell line hcmec/d3, a human blood-brain barrier model.

Functional expression of a proton-coupled organic cation (H+/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model. Keita Shimomura, Takashi Okura, Sayaka Kato, Pierre-Olivier Couraud, Jean-Michel Schermann, Tetsuya Terasaki, Yoshiharu Deguchi To cite this version: Keita Shimomura, Takashi Okura, Sayaka Kato, Pierre-Olivier Couraud, Jean-Michel Scher-mann, et al. Functional expression of a proton-coupled organic cation (H+/OC) antiporter inhuman brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model.Fluids and Barriers of the CNS, BioMed Central, 2013, 10 (1), pp.8. <10.1186/2045-8118-10-8>. <inserm-00785327>

Microsoft word - obesity november 2014.docx

ACUPUNCTURE AND OBESITY About obesity Around 60% of adults in England are either overweight or obese (DOH 2011), and 2% are morbidly obese (Body Mass Index (BMI) above 40kg/m2) (Information Centre 2008). In fact, if present trends continue, 60% of all men, 50% of all women, and 25% of all children will be obese by 2050. Being obese is associated with morbidity (e.g. type 2 diabetes mellitus, certain cancers, cardiovascular and musculoskeletal diseases) and premature death (Maggard 2005; Reeves 2007; Flegal 2007; Renehan 2008). Weight loss can reduce such problems and improve quality of life.