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\title{Potentially inappropriate prescribing in middle-aged adults: A
significant problem with a lack of action and evidence to address it.}



\author[1]{Michael Naughton}%
\author[2]{Frank Moriarty}%
\author[2]{Patrick Redmond}%
\affil[1]{Queen Mary University of London}%
\affil[2]{Royal College of Surgeons in Ireland}%


\vspace{-1em}



  
  \date{May 26, 2024}


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Letter to Editor:

Title:

Potentially inappropriate prescribing in middle-aged adults: A
significant problem with a lack of action and evidence to address it.

Authors: Dr Michael Naughton\textsuperscript{1}, Frank
Moriarty\textsuperscript{2}, Professor Patrick
Redmond\textsuperscript{3}

Author Affiliation:

\textsuperscript{1} The Clinical Effectiveness Group, Wolfson Institute
of Population Health, Queen Mary University of London

\textsuperscript{2} School of Pharmacy and Biomolecular Sciences, RCSI
University of Medicine \& Health Sciences

\textsuperscript{3} Department of General Practice, RCSI University of
Medicine \& Health Sciences

Word Count: 652

Key words: Potentially inappropriate prescribing, middle-aged adults,
intervention, medicines optimisation

Dear Dr Serge Cremers,

Potentially inappropriate prescribing (PIP), prescribing where the
potential harms outweigh the potential benefits, or where a medication
that a patient would benefit from is not prescribed, is an important
healthcare challenge. PIP has been well characterised among older adults
and is linked to adverse drug reactions (ADRs), hospitalisations, and
increased healthcare costs {[}1{]}. While studies have been conducted to
address PIP in older adults, middle-aged adults remain overlooked
despite also being vulnerable to PIP due to age-related chronic
conditions {[}2{]}.

Our recently published systematic review showed that PIP is common in
middle-aged adults, with an estimated 38\% being exposed to PIP annually
{[}3{]}. PIP in middle-aged adults is known to occur in higher risk and
disadvantaged groups? those with multimorbidity, polypharmacy, and those
from deprived areas {[}4{]}. It has been shown to be associated with
ADRs {[}5{]}, and may be associated with increased healthcare
utilisation {[}6{]}. A further study by our team, examined the cost of
PIP in 1.2 million middle-aged adults in South London, finding that the
total cost of PIP in this age group across six years was \selectlanguage{ngerman}£2.8 million.
The cost of adequate alternative prescribing would be £2.2 million, a
cost-saving of approximately £553,874 compared with PIP {[}7{]}.

Following on from these studies, we conducted a further systematic
search (unpublished) to examine interventions to reduce this
prescribing. Searches were conducted in MEDLINE, EMBASE, CINAHL,
Cochrane library, ProQuest, Web of Science, OpenGrey,
Clinicaltrials.gov, and the WHO Clinical Trials Registry Platform. All
English language studies that included adults aged 45-64 years, applied
explicit PIP criteria, and implemented an intervention to reduce PIP and
were published by June 2022, were eligible. In total, 12,384 studies
underwent title and abstract screening with 248 articles identified for
full text screening, however ultimately none met our inclusion criteria.

Our search has revealed a literature gap, with no studies having been
conducted with interventions aiming to reduce PIP in middle-aged adults.
Conversely, there are numerous interventional studies to reduce PIP in
older adults {[}8, 9{]}. PIP in older adults has a similar
prevalence{[}10{]}, but in absolute terms the largest burden of PIP
exists in middle-aged adults due to the larger population size.
Intervening earlier in middle age may allow patients' medicines to be
optimised and avoid adverse outcomes as they age.

Furthermore, the benefits of targeting high risk prescribing independent
of age, rather than concentrating only on older adults, have been
demonstrated by multiple studies. Concentrating on high-risk prescribing
across all age groups, these studies have shown interventions can reduce
high risk prescribing, and associated adverse outcomes such as
GI-bleeds, heart failure, and hospital admissions {[}11{]}. The PINCER
intervention has also shown that interventions to reduce high risk
prescribing can be highly cost effective {[}12{]}. The current,
extremely welcome, deprescribing initiatives
(https://deprescribing.org/) are applicable beyond older adults and
could also be used to benefit the middle-aged in particular. Therefore,
as well as extending interventions to middle-aged people specifically,
it is also worth considering a whole population approach to high risk
prescribing or PIP, given the demonstrated successes and cost
effectiveness of these approaches previously.

As practising clinical academics, we are concerned about the lack of
policy and research activity to develop interventions to reduce PIP in
middle-aged adults. This is an issue effecting a significant proportion
of the middle-aged population and it is vital to understand how to
reduce this prescribing to avoid preventable harms and unnecessary cost
to the health service. I urge the British Journal of Clinical
Pharmacology to prioritise the issue of appropriate prescribing outside
of the narrow focus on older adults by encouraging submissions and
facilitating discourse among researchers, practitioners, and
policymakers. This would contribute to our understanding of PIP in other
age groups, including middle-aged adults, and help to develop
interventions to address the issue in wider patient groups. I hope this
letter serves as a catalyst for discussion and research on this pressing
issue.

Yours sincerely,

References:

1. O'Connor MN, Gallagher P, O'Mahony D. Inappropriate Prescribing
Criteria, Detection and Prevention. Drugs Aging 2012; 29: 437-52.

2. Gallagher PF, O'Connor MN, O'Mahony D. Prevention of Potentially
Inappropriate Prescribing for Elderly Patients: A Randomized Controlled
Trial Using STOPP/START Criteria. Clin Pharmacol Ther 2011; 89: 845-54.

3. Naughton M, Moriarty F, Bailey J, Bowen L, Redmond P, Molokhia M. A
systematic review of the prevalence, determinants, and impact of
potentially inappropriate prescribing in middle-aged adults. Drugs \&
Therapy Perspectives 2022; 38: 21-32.

4. Khatter A, Moriarty F, Ashworth M, Durbaba S, Redmond P. Prevalence
and Predictors of Potentially Inappropriate Prescribing in Middle-Aged
Adults: Repeated Cross-Sectional Study. British Journal of General
Practice 2021: BJGP.2020.1048.

5. Smeaton T, McElwaine P, Cullen J, Santos-Martinez MJ, Deasy E,
Widdowson M, Grimes TC. A prospective observational pilot study of
adverse drug reactions contributing to hospitalization in a cohort of
middle-aged adults aged 45-64 years. Drugs and Therapy Perspectives
2020; 36: 123-30.

6. Moriarty F, Cahir C, Bennett K, Hughes CM, Kenny RA, Fahey T.
Potentially inappropriate prescribing and its association with health
outcomes in middle-aged people: a prospective cohort study in Ireland.
Bmj Open 2017; 7: 11.

7. Jayesinghe R, Moriarty F, Khatter A, Durbaba S, Ashworth M, Redmond
P. Cost outcomes of potentially inappropriate prescribing in middle-aged
adults: A Delphi consensus and cross-sectional study. British Journal of
Clinical Pharmacology 2022; 88: 3404-20.

8. Spinewine A, Schmader KE, Barber N, Hughes C, Lapane KL, Swine C,
Hanlon JT. Prescribing in elderly people 1 - Appropriate prescribing in
elderly people: how well can it be measured and optimised? Lancet 2007;
370: 173-84.

9. Clyne B, Fitzgerald C, Quinlan A, Hardy C, Galvin R, Fahey T, Smith
SM. Interventions to Address Potentially Inappropriate Prescribing in
Community-Dwelling Older Adults: A Systematic Review of Randomized
Controlled Trials. J Am Geriatr Soc 2016; 64: 1210-22.

10. Liew TM, Lee CS, Goh SKL, Chang ZY. The prevalence and impact of
potentially inappropriate prescribing among older persons in primary
care settings: multilevel meta-analysis. Age Ageing 2020; 49: 570-79.

11. Dreischulte T, Donnan P, Grant A, Hapca A, McCowan C, Guthrie B.
Safer Prescribing --- A Trial of Education, Informatics, and Financial
Incentives. New England Journal of Medicine 2016; 374: 1053-64.

12. Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M,
Elliott RA, Howard R, Kendrick D, Morris CJ, Prescott RJ, Swanwick G,
Franklin M, Putman K, Boyd M, Sheikh A. A pharmacist-led information
technology intervention for medication errors (PINCER): a multicentre,
cluster randomised, controlled trial and cost-effectiveness analysis.
Lancet 2012; 379: 1310-19.

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