Janine A. Cooper

Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review

Objective To summarise the findings of an updated Cochrane review of interventions aimed at improving the appropriate use of polypharmacy in older people. Design Cochrane systematic review. Multiple electronic databases were searched including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (from inception to November 2013). Hand searching of references was also performed. Randomised controlled trials (RCTs), controlled clinical trials, controlled before-and-after studies and interrupted time series analyses reporting on interventions targeting appropriate polypharmacy in older people in any healthcare setting were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation). Setting All healthcare settings. Participants Older people (≥65 years) with ≥1 long-term condition who were receiving polypharmacy (≥4 regular medicines). Primary and secondary outcome measures Primary outcomes were the change in prevalence of appropriate polypharmacy and hospital admissions. Medication-related problems (eg, adverse drug reactions), medication adherence and quality of life were included as secondary outcomes. Results 12 studies were included: 8 RCTs, 2 cluster RCTs and 2 controlled before-and-after studies. 1 study involved computerised decision support and 11 comprised pharmaceutical care approaches across various settings. Appropriateness was measured using validated tools, including the Medication Appropriateness Index, Beers’ criteria and Screening Tool of Older Persons Prescriptions (STOPP)/ Screening Tool to Alert doctors to Right Treatment (START). The interventions demonstrated a reduction in inappropriate prescribing. Evidence of effect on hospital admissions and medication-related problems was conflicting. No differences in health-related quality of life were reported. Conclusions The included interventions demonstrated improvements in appropriate polypharmacy based on reductions in inappropriate prescribing. However, it remains unclear if interventions resulted in clinically significant improvements (eg, in terms of hospital admissions). Future intervention studies would benefit from available guidance on intervention development, evaluation and reporting to facilitate replication in clinical practice.

Effectiveness of a Multifaceted Intervention for Potentially Inappropriate Prescribing in Older Patients in Primary Care: A Cluster-Randomized Controlled Trial (OPTI-SCRIPT Study)

PURPOSE Potentially inappropriate prescribing (PIP) is common in older people and can result in increased morbidity, adverse drug events, and hospitalizations. The OPTI-SCRIPT study (Optimizing Prescribing for Older People in Primary Care, a cluster-randomized controlled trial) tested the effectiveness of a multifaceted intervention for reducing PIP in primary care. METHODS We conducted a cluster-randomized controlled trial among 21 general practitioner practices and 196 patients with PIP. Intervention participants received a complex, multifaceted intervention incorporating academic detailing; review of medicines with web-based pharmaceutical treatment algorithms that provide recommended alternative-treatment options; and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions. We performed intention-to-treat analysis using random-effects regression. RESULTS All 21 practices and 190 patients were followed. At intervention completion, patients in the intervention group had significantly lower odds of having PIP than patients in the control group (adjusted odds ratio = 0.32; 95% CI, 0.15–0.70; P = .02). The mean number of PIP drugs in the intervention group was 0.70, compared with 1.18 in the control group (P = .02). The intervention group was almost one-third less likely than the control group to have PIP drugs at intervention completion, but this difference was not significant (incidence rate ratio = 0.71; 95% CI, 0.50–1.02; P = .49). The intervention was effective in reducing proton pump inhibitor prescribing (adjusted odds ratio = 0.30; 95% CI, 0.14–0.68; P = .04). CONCLUSIONS The OPTI-SCRIPT intervention incorporating academic detailing with a pharmacist, and a review of medicines with web-based pharmaceutical treatment algorithms, was effective in reducing PIP, particularly in modifying prescribing of proton pump inhibitors, the most commonly occurring PIP drugs nationally.

Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

IntroductionRecent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.MethodsA cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).ResultsAfter breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.ConclusionsOverall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.

Going beyond the numbers - a call to redefine polypharmacy

‘Polypharmacy’ has often been used to describe the use of multiple medications and has been noted as ‘one of the most pressing prescribing challenges’ 1. There is no accepted definition as to what number of drugs constitutes polypharmacy, with some authorities proposing four or five medications 2–4. Polypharmacy has also been viewed negatively and been described as the ‘administration of more medicines than are clinically indicated, representing unnecessary drug use’ 5. However, there is growing recognition that polypharmacy may be entirely appropriate, as evidence-based guidelines advocate the use of more than one drug in the management of long term conditions, e.g. hypertension 6. This situation may be compounded further by the presence of two or more long term conditions i.e. multimorbidity 7. A recent study by Barnett et al. has shown that 64.9% of those aged over 65 years had a mean of 2.6 multimorbidities and 81.5% of those over 85 years were multimorbid and had a mean of 3.62 long term conditions 7. Although multimorbidity is more prevalent with increasing age, the Barnett study showed 30.4% of those aged between 45 and 64 years were living with two or more chronic conditions (mean of 1.18 morbidities) 7, all of which may require drug treatment. Therefore, polypharmacy is arguably the new paradigm for prescribing 8, being driven by multimorbidity and the plethora of evidence-based guidelines for the management of long term conditions. Aronson has described polypharmacy as having a dual meaning: ‘too many drugs’, or ‘many drugs’, and in the case of the latter, this may be entirely appropriate 9. Hence, there has been a call for a change in emphasis from inappropriate polypharmacy (‘too many drugs’) to the prescribing of appropriate polypharmacy (‘many drugs’). This is the challenge that faces healthcare professionals (HCPs) who care for older people, particularly general practitioners (GPs) who prescribe most of their medication. Payne et al. 10 have contributed a timely paper on the potential hazards of polypharmacy, highlighting that although unplanned hospitalization was strongly associated with the number of regular medicines, the effect was reduced in patients with multiple conditions, with only the most extremes levels of polypharmacy associated with increased admissions. This is an important finding as it goes some way towards dispelling the myth that polypharmacy is not just about numbers of drugs and is not always associated with poor outcomes. This study made use of Scottish primary care data for just over 180 000 patients (long term clinical conditions and details on regularly prescribed medication) and linked these data with national hospital admissions information for the following year. The study has examined a more inclusive population, ranging in age from 20 years and over. Interestingly, the authors did not attempt to define polypharmacy based on the numbers of drugs, recognizing the lack of consensus as to what constitutes polypharmacy. Rather, they categorized medicines into ranges (e.g. 1–3, 4–6) which allowed for the non-linear effects of increasing the number of medicines. The term polypharmacy was still used to convey the use of multiple medications, but not necessarily in a pejorative way. They employed a list of 40 physical and mental conditions to develop a measure of multimorbidity, which was inclusive of morbidities that had been previously recognized as core to such a measure, those that were included in the United Kingdom (UK) GP contract (the Quality and Outcomes Framework-QOF) and those considered important for health care planning in the context of Scotland. Using the secondary care data, the authors identified one unplanned hospital admission (in the year following a cut-off point for prescribing and clinical information) which was defined as an emergency or urgent according to the condition of the patient as assessed by a doctor. Following linkage between these two datasets, regression analysis revealed, unsurprisingly, that increasing numbers of regular medicines were seen with increasing multimorbidity. Unplanned admissions were more common as the numbers of prescribed medicines increased. However, the strength of the association was greatly reduced in individuals with more conditions. For example, those patients with six or more conditions taking 4–6 medicines, were no more likely to have an unplanned admission than those taking 1–3 medicines. In contrast, those patients with six or more conditions taking no medicines, were more likely to be admitted than those taking 1–3 medicines. This suggests that appropriate drug management using several drugs in those with multiple conditions may prevent unnecessary hospitalizations and highlights the importance of ensuring that all clinical conditions receive appropriate treatment. As stated in the Discussion of the paper 10, the study ‘highlights the importance of considering polypharmacy in the clinical context for which medications are being prescribed.’ This calls into question the continuing reliance of judging the quality of prescribing on the numbers of drugs alone, although numbers may signal the need for a review. Considering the clinical context requires having access to high quality data, and clearly, dataset linkage should be strongly encouraged to facilitate this type of research. The authors also call for a re-framing of the term ‘polypharmacy’ and we would support this. A Cochrane review published in 2012 4 attempted to go some way to do this, by using the term ‘appropriate polypharmacy’ and sought to identify studies which were effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. Ten studies were identified which produced changes in reducing inappropriate prescribing and medication-related problems, but it was unclear if the interventions resulted in significant clinical improvement. Almost all included studies used a number to define polypharmacy. Going beyond the numbers in terms of polypharmacy seems a natural progression in the light of this study, provided that access to comprehensive, high quality clinical information is guaranteed. Multimorbidity is increasing throughout the population and central to its appropriate management will be the prescribing of multiple long term medications. Clinical guidelines in the future will need to consider the implications of multimorbidity for drug treatment, with the recognition that many drugs may be entirely appropriate, and in that sense, polypharmacy should be strongly encouraged.

The development of the PROMPT (PRescribing Optimally in Middle-aged People’s Treatments) criteria

BackgroundWhilst multimorbidity is more prevalent with increasing age, approximately 30% of middle-aged adults (45-64 years) are also affected. Several prescribing criteria have been developed to optimise medication use in older people (≥65 years) with little focus on potentially inappropriate prescribing (PIP) in middle-aged adults. We have developed a set of explicit prescribing criteria called PROMPT (PRescribing Optimally in Middle-aged People’s Treatments) which may be applied to prescribing datasets to determine the prevalence of PIP in this age-group.MethodsA literature search was conducted to identify published prescribing criteria for all age groups, with the Project Steering Group (convened for this study) adding further criteria for consideration, all of which were reviewed for relevance to middle-aged adults. These criteria underwent a two-round Delphi process, using an expert panel consisting of general practitioners, pharmacists and clinical pharmacologists from the United Kingdom and Republic of Ireland. Using web-based questionnaires, 17 panellists were asked to indicate their level of agreement with each criterion via a 5-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree) to assess the applicability to middle-aged adults in the absence of clinical information. Criteria were accepted/rejected/revised dependent on the panel’s level of agreement using the median response/interquartile range and additional comments.ResultsThirty-four criteria were rated in the first round of this exercise and consensus was achieved on 17 criteria which were accepted into the PROMPT criteria. Consensus was not reached on the remaining 17, and six criteria were removed following a review of the additional comments. The second round of this exercise focused on the remaining 11 criteria, some of which were revised following the first exercise. Five criteria were accepted from the second round, providing a final list of 22 criteria [gastro-intestinal system (n = 3), cardiovascular system (n = 4), respiratory system (n = 4), central nervous system (n = 6), infections (n = 1), endocrine system (n = 1), musculoskeletal system (n = 2), duplicates (n = 1)].ConclusionsPROMPT is the first set of prescribing criteria developed for use in middle-aged adults. The utility of these criteria will be tested in future studies using prescribing datasets.

Potentially Inappropriate Prescribing Among People with Dementia in Primary Care: A Retrospective Cross-Sectional Study Using the Enhanced Prescribing Database

BACKGROUND Little is known about prescribing appropriateness for community-dwelling people with dementia (PWD). OBJECTIVE To estimate potentially inappropriate prescribing (PIP) prevalence among PWD in primary care in Northern Ireland, and to investigate associations between PIP, polypharmacy, age, and gender. METHODS A retrospective cross-sectional study was conducted, using data from the Enhanced Prescribing Database. Patients were eligible if a medicine indicated for dementia management was dispensed to them during 1 January 2013-31 December 2013. Polypharmacy was indicated by use of ≥4 repeat medications from different drug groups. A subset of the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria, comprising 36 indicators, was applied to the dataset. Overall prevalence of PIP and the prevalence per each STOPP criterion was calculated as a proportion of all eligible persons in the dataset. Logistic regression was used to investigate associations between PIP, polypharmacy, age, and gender. RESULTS The study population comprised 6826 patients. Polypharmacy was observed in 81.5% (n = 5564) of patients. PIP prevalence during the study period was 64.4% (95% CI 63.2- 65.5; n = 4393). The most common instance of PIP was the use of anticholinergic/antimuscarinic medications (25.2%; 95% CI 24.2-26.2; n = 1718). In multivariable analyses, both polypharmacy and gender (being female) were associated with PIP, with odds ratios of 7.6 (95% CI 6.6-8.7) and 1.3 (95% CI 1.2-1.4), respectively. No association was observed between PIP and age, after adjustments for gender and polypharmacy. CONCLUSION This study identified a high prevalence of PIP in community-dwelling PWD. Future interventions may need to focus on certain therapeutic categories and polypharmacy.

Non-steroidal anti-inflammatory drug use and cervical cancer risk: A case-control study using the Clinical Practice Research Datalink

PURPOSE Non-steroidal anti-inflammatory drugs (NSAIDs) have many anticarcinogenic properties via the inhibition of cyclooxygenase 2 (COX-2). Only one study, a cohort study examining risk of all cancers, investigated their role in cervical cancer with inconsistent findings between non-aspirin NSAIDs and aspirin. The aim of this study was to further investigate NSAID/aspirin use and cervical cancer risk. METHODS Using the United Kingdom Clinical Practice Research Datalink, 724 women diagnosed with cervical cancer between 1 January, 1995 and December 2010 were compared to 3479 women (without cervical cancer) matched on year of birth and general practice. Conditional logistic regression analysis adjusted for smoking, sexually transmitted infections, HRT and contraceptive use, was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for cervical cancer risk among users of any oral NSAIDs, non-aspirin NSAIDs and aspirin, as assessed from primary care prescribing data. RESULTS Excluding the year prior to diagnosis, there was no association in adjusted analyses between ever vs. never use of an NSAID (OR 0.92, 95% CI 0.77-1.09), non-aspirin NSAID (OR 0.95, 95% CI 0.80-1.13) or low-dose aspirin (OR 1.07, 0.80-1.44) and cervical cancer risk. In analysis of daily defined doses, there was no association with cervical cancer risk comparing the highest users to non-users of NSAIDs (OR 0.98, 95% CI 0.69-1.39) or non-aspirin NSAIDs (OR 1.00, 95% CI 0.70-1.43) or low-dose aspirin (OR 1.04, 95% CI 0.59-1.81). CONCLUSION This large historical cohort study found no evidence of an association between non-aspirin NSAID or aspirin use and cervical cancer risk.

PIPc study: development of indicators of potentially inappropriate prescribing in children (PIPc) in primary care using a modified Delphi technique

Objective There is limited evidence regarding the quality of prescribing for children in primary care. Several prescribing criteria (indicators) have been developed to assess the appropriateness of prescribing in older and middle-aged adults but few are relevant to children. The objective of this study was to develop a set of prescribing indicators that can be applied to prescribing or dispensing data sets to determine the prevalence of potentially inappropriate prescribing in children (PIPc) in primary care settings. Design Two-round modified Delphi consensus method. Setting Irish and UK general practice. Participants A project steering group consisting of academic and clinical general practitioners (GPs) and pharmacists was formed to develop a list of indicators from literature review and clinical expertise. 15 experts consisting of GPs, pharmacists and paediatricians from the Republic of Ireland and the UK formed the Delphi panel. Results 47 indicators were reviewed by the project steering group and 16 were presented to the Delphi panel. In the first round of this exercise, consensus was achieved on nine of these indicators. Of the remaining seven indicators, two were removed following review of expert panel comments and discussion of the project steering group. The second round of the Delphi process focused on the remaining five indicators, which were amended based on first round feedback. Three indicators were accepted following the second round of the Delphi process and the remaining two indicators were removed. The final list consisted of 12 indicators categorised by respiratory system (n=6), gastrointestinal system (n=2), neurological system (n=2) and dermatological system (n=2). Conclusions The PIPc indicators are a set of prescribing criteria developed for use in children in primary care in the absence of clinical information. The utility of these criteria will be tested in further studies using prescribing databases.

Pharmacists’ perceptions of the barriers and facilitators to successful medicines management for people with dementia in primary care

Abstract of paper presented at the Health Services Research and Pharmacy Practice Conference, University of Nottingham, UK, 10–11 April 2017In recent years, self-care has been in the forefront of UK health policy [1], with community pharmacies being promoted as a first point of contact for patients [2], when seeking advice for the treatment of a variety of conditions and minor ailments. As more medicines have become available without prescription this has led to community pharmacists dealing with a wider range of presenting problems and spending more time on making clinical decisions. Aims / objectives The area of how community pharmacists make a clinical diagnosis is under-researched. The aim of this exploratory study was to gain an initial insight on how community pharmacists make clinical decisions in order to reach a diagnosis. Method A qualitative methodology was employed where semi-structured, face-to-face interviews were conducted with community pharmacists that had been practicing for at least six months at the time of the interviews and did not hold, or were working towards, a prescribing qualification. Pharmacists were identified through snow balling sampling and consent sheets sent to their pharmacies’ registered address. Pharmacists who returned completed consent forms were recruited to the study. All interviews were audio recorded and transcribed ad verbatim. Interviews were analysed, with a team-based approach, using a clinical reasoning based framework analysis to identify themes and subthemes. Ethical approval was granted by the ethics committee at the University of Wolverhampton. Results Eight interviews were conducted across England, with five male and three female pharmacists, who had been practicing for periods ranging from one to forty years. The major theme that emerged from the analysis was the poor diagnostic knowledge and ability of the pharmacists and a non-evidence based approach to decision-making. Pharmacists constantly used and overly relied on mnemonic methods both for diagnostic purposes and product selection. Their motives within consultations appeared to be establishing an appropriate product to recommend, rather than the need to establish a diagnosis, and the inability to differentiate between the two processes. However, they did have a sense of the limitations of the methods they used and an awareness for the need to ‘delve deeper’ during consultations but could not articulate how or why this was the case. Themes and sub-themes are explained using confirmatory quotes from the data. Discussion or Conclusion The findings of this study suggest that even though community pharmacists are tasked with advising symptom-presenting patients, their poor clinical reasoning skills are preventing them from reaching appropriate diagnoses. In order for community pharmacists to better perform this role, greater emphasis should be given in teaching and practicing clinical reasoning skills during their studies and through continuous professional development. The study is limited by its small sample size. 1. Department of Health. The NHS Plan. A Plan for Investment, A Plan for Reform [Internet]. London: National Health Service; 2000 [cited 6 October 2012]. Available from: http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/publicationsandstatistics/publications/publicationspolicyandguidance/dh_4002960 2. Royal Pharmaceutical Society. Improving Urgent and Emergency care through better use of pharmacists [Internet]; 2014 [cited 5 October 2016]. Available from: http://www.rpharms.com/policy-pdfs/urgent-and-emergency-care.pdf

The development of a core outcome set for medicines management interventions in people with dementia

Focal Points: Aim was to assess the impact of an educational intervention delivered by community pharmacists to improve self-management for people with mild to moderate psoriasis. Educational advice from pharmacists improved significantly patient knowledge, disease severity and quality of life. Community pharmacists could provide an important contribution to the care of patients with psoriasis Introduction: Psoriasis is a chronic inflammatory skin condition affecting up to 3% of the population in the UK. Most patients have mild to moderate disease which can be managed in primary care with topical therapies. Studies suggest that patients want, but rarely get, advice on the use of prescribed treatments. Community pharmacists have developed a more clinically focused supportive role with patients, though their role in helping those with long-term dermatological conditions is less clear. The aim of this research was to assess the impact of an educational intervention delivered by community pharmacists to improve self-management for people with mild to moderate psoriasis. Methods: Seven study pharmacies were selected based on their location (urban, rural etc.) to provide a range of different settings and pharmacists recruited via a comprehensive research network. Each was given a training guide on the management of psoriasis, with emphasis on patient education. Pharmacists identified patients prescribed topical psoriasis treatments, invited them to participate in the study (opportunistically or via a letter of invite) and obtained informed consent. During a face-to-face consultation in the pharmacy, the pharmacists provided education on psoriasis and its management and arranged a follow-up consultation 6 weeks later. During the consultations, pharmacists assessed patients’ knowledge and understanding of psoriasis and its management using the person-centred dermatology self-care index (PEDESI). This ten item tool evaluates the educational and support needs of those with long-term skin conditions. Pharmacists assigned an “ability score” for each item reflecting understanding. Scores were summed to give an overall score ranging from zero (worse state) to 30 (best state). In addition, disease severity and quality of life were self-assessed by patients using the self-assessed psoriasis and severity index (SAPASI) and dermatology quality of life index (DLQI) respectively. The primary outcome measure was the change in PEDESI score at at 6 weeks and secondary outcomes were changes in SAPASI and DLQI values. The study was approved by an NHS ethics committee. Results: Pharmacists recruited a total of 47 patients ̧ though 5 were lost to follow-up. The number of patients recruited per pharmacy ranged from 1 to 10. There was a significant increase in mean PEDESI scores (25.15 versus 17.78 P < 0.001) at 6 weeks compared to baseline. The increased mean PEDESI scores was mirrored by a rise in ability scores across all questions. Both SAPASI (11.60 versus 7.74, P < 0.001) and DLQI (7.21 versus 4.14, P < 0.001) scores improved significantly and 17 patients experienced a clinically meaningful change in quality of life, defined as a four-point improvement on the scale. Discussion: Pharmacist-led educational advice to patients with psoriasis improved disease and treatment knowledge, reducing disease severity and the impact on quality of life. Though limited by the sample size and a single follow-up, this is the first study to explore the potential role of pharmacists in helping to facilitate effective self-management in patients with long-term skin conditions. The results suggest a potential role for community pharmacists in the care of patients with psoriasis. Further studies are needed to explore the costeffectiveness of the intervention on patient-related disease outcomes compared to other services.