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