The aims of the current review were to identify, in the context of people with acquired communication disorders: factors which influence medication adherence, current interventions targeting medication adherence, and how medication adherence is currently measured. This study was conducted and reported in accordance with both PRISMA and SWiM guidelines. Two authors independently screened the results of a literature search, assessed risk of bias, and extracted relevant data. Eight studies were identified for inclusion. Four of the studies presented information relating to current interventions which target medication adherence for people with acquired communication disorders. Four of the studies investigated factors which influence medication adherence for people with acquired communication disorders. Seven of these eight studies outlined methods used for measuring medication adherence. The results of this review indicate that patient related factors are most associated with medication non-adherence in a population with acquired communication disorders, followed by socio-economic factors and medication-related factors. Despite the recognised importance of medication adherence, no gold standard of assessment or intervention currently exist for this population. Half of the included studies replaced patients with communication difficulties with caregiver proxies, thus reducing opportunities for patients to participate meaningfully in research. The term “acquired communication disorders” encompasses a range of conditions with diverse aetiologies, presentations, and needs, and future research should be tailored to specific patient groups most at risk of medication non-adherence, namely those with aphasia and cognitive-communication impairments. Patients should be empowered to participate in future research to ensure the literature accurately represents their lived experience.

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 Naughton1, Frank Moriarty2, Professor Patrick Redmond3Author Affiliation:1 The Clinical Effectiveness Group, Wolfson Institute of Population Health, Queen Mary University of London2 School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine & Health Sciences3 Department of General Practice, RCSI University of Medicine & Health SciencesWord Count: 652Key words: Potentially inappropriate prescribing, middle-aged adults, intervention, medicines optimisationDear 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 £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.

Interventions to promote deprescribing are an important focus of research. Key decisions for such interventions are whether to target one or multiple medicines, and whether the intervention scope is deprescribing, or also extends to other aspects of medicines optimisation. This article reflects on how these decisions impact on developing interventions and measuring outcomes. Many behavioural strategies are common to deprescribing and medicines optimisation, however operationalisation may differ. Aspects to consider include the burden of multiple simple interventions versus one complex intervention, the extent to which the approach to deprescribing can be specified as part of the intervention, and variability in how the intervention is delivered across patients and providers. Outcomes should be selected based on the intervention target and scope and the audience for whom evidence is being produced. These may include medication changes, and process outcomes to assess intervention delivery. Targeting single medications may allow for a focus on specific clinical or symptom-related outcomes, rather than more general outcomes such as adverse drug reactions. Cost-related outcomes are also important to inform implementation decisions, and modelling approaches may be more feasible for interventions targeting single medications.

Deprescribing is an essential component of safe prescribing, especially for people with higher levels of polypharmacy. Identifying individuals prepared to consider medicine changes may facilitate deprescribing-orientated reviews. We aimed to explore the relationship between revised patient attitudes towards deprescribing (rPATD) scores and medication changes in older people prescribed ≥15 medicines. A secondary analysis of rPATD scores and prescription data from a cluster randomised controlled trial of a GP-delivered, deprescribing-orientated medication review was conducted. The association between number of medicines stopped, started and changed and baseline rPATD scores was assessed using Poisson regression adjusting for patient age, gender, study group allocation, baseline number of medicines and effects of clustering. Participants (n=404) had a mean age of 76.4 years and were prescribed a mean of 17.1 medicines at baseline. Willingness to stop a medicine was associated with higher rates of both deprescribing (IRR: 1.40; 95%CI: 1.06-1.84) and initiating medicines (IRR: 1.43; 95%CI: 1.09-1.88). Satisfaction with current medicines was associated with a lower rate of deprescribing (IRR: 0.69; 95%CI: 0.57-0.85). The rPATD questionnaire could be used as part of a deprescribing intervention to identify participants who may be prepared to engage in deprescribing, enabling more efficient use of clinician time during complex consultations.

BackgroundNumber of medicines and medicines appropriateness are often used as outcome measures to evaluate the effectiveness of deprescribing interventions. The aim of this study was to evaluate changes in prescribing, potentially inappropriate prescriptions (PIP) and prescribing of low-value medicines during the SPPiRE trial.MethodsWe retrospectively analysed trial prescription data from 51 general practices with 404 participants aged ≥65 years and prescribed ≥15 repeat medicines. Repeat medications at baseline and follow-up (~1 year later) were assigned Anatomical Therapeutic Classification (ATC) codes. Outcomes were the most commonly prescribed and potentially inappropriately prescribed drug groups, the most frequently discontinued or initiated drug groups and the number of changes per person between baseline and follow-up.Results There were 7,051 medicines prescribed to 404 participants at baseline. There was a median of 17 medicines (IQR 15-19) at baseline and 16 (IQR 14-19) at follow-up. PIP represented 17.1% of prescriptions at baseline and 15.7% (n=6,777) at follow-up. There were reductions in the prescription of most drug groups with the largest reduction in antiplatelet prescriptions. Considering medication discontinuations, initiations and switches, there was a median of five medication changes per person (range 0-30, IQR 3-9) by follow-up. There were 95 low-value prescriptions at baseline reducing to 78 at follow-up.ConclusionThe number of medication changes per person was not reflected by summarising medication count at two time points, highlighting the complexity of prescribing for patients with polypharmacy. Frequent medication changes has potentially important implications for patients in terms of adherence and medication safety.Key words: Multimorbidity, polypharmacy, cluster randomised controlled trial, deprescribing, potentially inappropriate prescribingThe SPPiRE trial was registered prospectively on the ISRCTN registry (ISRCTN12752680).

Abstract Background: The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community-dwelling adults. Methods: Systematic review reported in line with the PRISMA guidelines and pre-registered with PROSPERO. Electronic databases (Medline (Ovid), EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: Community-dwelling adults; Risk-prescription medication; Outcomes-initiation of new medicine to ‘treat’ or reduce ADR risk; Study type-cohort, cross-sectional, case-control and case-series studies. Title/abstract screening, full-text screening, data extraction and methodological quality assessment was conducted independently in duplicate. A narrative synthesis was conducted. Results: A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11,593,989 participants and 15 studies examined older adults specifically (≥60 years). Seventy-eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic (n=5), amiodarone to levothyroxine (n=5), inhaled corticosteroid to topical antifungal (n=4), antipsychotic to anti-Parkinson drug (n=4), and acetylcholinesterase inhibitor to urinary incontinence drugs (n=4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Conclusion and implications: Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months. Word count: 245

Objectives To evaluate the benefits imparted by concurrent chemoradiotherapy (CCRT) and chemotherapy of any form to elderly head and neck cancer (HNC) patients in Ireland. Secondary outcomes included comparison of these benefits to the adult population and subgroup analysis by site. Design, setting, and participants A retrospective cohort study was conducted using 20 years of cancer registry data provided by the National Cancer Registry of Ireland. All HNC diagnosed from 1994-2014 were included. Cox multivariate regression analysis was applied to test for the benefits of CCRT and chemotherapy of any form in HNC. The primary outcome measures were cancer-specific and all-cause survival in months. Results Survival analysis showed an overall benefit to the use of CCRT in patients with advanced disease over 65 years, particularly when used for hypopharyngeal, oral cavity, oropharyngeal, and laryngeal malignancy, though the latter did not achieve statistical significance. Chemotherapy of any form conferred a survival benefit in elderly patients with hypopharyngeal, laryngeal, nasopharyngeal, and oropharyngeal cancer. Conclusion CCRT and chemotherapy of any form confer significant survival benefits to appropriately selected elderly HNC patients and should therefore not be withheld solely on the basis of age.