'I think we could probably do more': an interview study to explore community pharmacists' experiences and perspectives of frailty and optimising medicines use in frail older adults.

BACKGROUND: Community pharmacists potentially have an important role to play in identification of frailty and delivery of interventions to optimise medicines use for frail older adults. However, little is known about their knowledge or views about this role. AIM: To explore community pharmacists' knowledge of frailty and assessment, experiences and contact with frail older adults, and perceptions of their role in optimising medicines use for this population. METHODS: Semi-structured interviews conducted between March and December 2020 with 15 community pharmacists in Northern Ireland. Interviews were transcribed verbatim and analysed thematically. RESULTS: Three broad themes were generated from the data. The first, 'awareness and understanding of frailty', highlighted gaps in community pharmacists' knowledge regarding presentation and identification of frailty and their reluctance to broach potentially challenging conversations with frail older patients. Within the second theme, 'problem-solving and supporting medication use', community pharmacists felt a large part of their role was to resolve medicines-related issues for frail older adults through collaboration with other primary healthcare professionals but feedback on the outcome was often not provided upon issue resolution. The third theme, 'seizing opportunities in primary care to enhance pharmaceutical care provision for frail older adults', identified areas for further development of the community pharmacist role. CONCLUSIONS: This study has provided an understanding of the views and experiences of community pharmacists about frailty. Community pharmacists' knowledge deficits about frailty must be addressed and their communication skills enhanced so they may confidently initiate conversations about frailty and medicines use with older adults.

Potentially inappropriate prescribing for people with dementia in ambulatory care: a cross-sectional observational study.

BACKGROUND: Studies have shown that potentially inappropriate prescribing (PIP) is highly prevalent among people with dementia (PwD) and linked to negative outcomes, such as hospitalisation and mortality. However, there are limited data on prescribing appropriateness for PwD in Saudi Arabia. Therefore, we aimed to estimate the prevalence of PIP and investigate associations between PIP and other patient characteristics among PwD in an ambulatory care setting. METHODS: A cross-sectional, retrospective analysis was conducted at a tertiary hospital in Saudi Arabia. Patients who were ≥ 65 years old, had dementia, and visited ambulatory care clinics between 01/01/2019 and 31/12/2021 were included. Prescribing appropriateness was evaluated by applying the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria. Descriptive analyses were used to describe the study population. Prevalence of PIP and the prevalence per each STOPP criterion were calculated as a percentage of all eligible patients. Logistic regression analysis was used to investigate associations between PIP, polypharmacy, age and sex; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Analyses were conducted using SPSS v27. RESULTS: A total of 287 PwD were identified; 56.0% (n = 161) were female. The mean number of medications prescribed was 9.0 [standard deviation (SD) ± 4.2]. The prevalence of PIP was 61.0% (n = 175). Common instances of PIP were drugs prescribed beyond the recommended duration (n = 90, 31.4%), drugs prescribed without an evidence-based clinical indication (n = 78, 27.2%), proton pump inhibitors (PPIs) for > 8 weeks (n = 75, 26.0%), and acetylcholinesterase inhibitors with concurrent drugs that reduce heart rate (n = 60, 21.0%). Polypharmacy was observed in 82.6% (n = 237) of patients and was strongly associated with PIP (adjusted OR 24.1, 95% CI 9.0-64.5). CONCLUSIONS: Findings have revealed a high prevalence of PIP among PwD in Saudi Arabia that is strongly associated with polypharmacy. Future research should aim to explore key stakeholders' experiences and perspectives of medicines management to optimise medication use for this vulnerable patient population.

Improving medication dispensing and counselling for patients with vision impairment: a qualitative study of pharmacist-reported barriers and facilitators.

BACKGROUND: People with vision impairment encounter many difficulties when it comes to medicines use. However, evidence indicates that there are major gaps in pharmaceutical care service provision worldwide and limited research on interventions to optimise medication use for this patient population. The Theoretical Domains Framework (TDF) provides a method for theoretically understanding individuals' behaviour and informing development of interventions. The aim of this research was to (a) identify the barriers and facilitators to the provision of medication dispensing and counselling services by pharmacists to patients with vision impairment, and (b) identify key TDF domains to be targeted in a future intervention. METHODS: Semi-structured interviews were conducted with pharmacists from different pharmacy practice settings/areas in Saudi Arabia. The 14-domain TDF was utilised as the theoretical lens through which pharmacists' behaviours were examined. Interviews were conducted in Arabic or English, either face-to-face or over the telephone based on the participant's preference. Following transcription, interviews conducted in Arabic were translated into English before analysis. Data analysis involved using the framework method and content analysis to identify important barriers and facilitators to the provision of dispensing and counselling services to those with vision impairment. Key TDF domains that could be targeted in a future intervention were then identified using a consensus-based approach. RESULTS: Twenty-six pharmacists were interviewed. Pharmacists' experience in pharmacy practice ranged from two to 28 years. A range of barriers and facilitators were highlighted as important in providing services to those with vision impairment. Eight domains were identified as 'key domains' including: 'Knowledge', 'Skills', 'Beliefs about capabilities', 'Goals', 'Memory, attention, and decision processes', 'Environmental context and resources', 'Social influences', and 'Behavioural regulation'. CONCLUSIONS: Barriers and facilitators identified by pharmacists will inform the development of an intervention to ensure its applicability to everyday practice. Future research will focus on the process of developing the proposed intervention through targeting key TDF domains to improve medication dispensing and counselling by pharmacists to patients with vision impairment.

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.

AIMS: There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. METHODS: A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. RESULTS: There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). CONCLUSIONS: In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

Antimicrobial resistance in urinary pathogens and culture-independent detection of trimethoprim resistance in urine from patients with urinary tract infection.

BACKGROUND: Although urinary tract infections (UTIs) are extremely common, isolation of causative uropathogens is not always routinely performed, with antibiotics frequently prescribed empirically. This study determined the susceptibility of urinary isolates from two Health and Social Care Trusts (HSCTs) in Northern Ireland to a range of antibiotics commonly used in the treatment of UTIs. Furthermore, we determined if detection of trimethoprim resistance genes (dfrA) could be used as a potential biomarker for rapid detection of phenotypic trimethoprim resistance in urinary pathogens and from urine without culture. METHODS: Susceptibility of E. coli and Klebsiella spp. isolates (n = 124) to trimethoprim, amoxicillin, ceftazidime, ciprofloxacin, co-amoxiclav and nitrofurantoin in addition to susceptibility of Proteus mirabilis (n = 61) and Staphylococcus saprophyticus (n = 17) to trimethoprim was determined by ETEST® and interpreted according to EUCAST breakpoints. PCR was used to detect dfrA genes in bacterial isolates (n = 202) and urine samples(n = 94). RESULTS: Resistance to trimethoprim was observed in 37/124 (29.8%) E. coli and Klebsiella spp. isolates with an MIC90 > 32 mg/L. DfrA genes were detected in 29/37 (78.4%) trimethoprim-resistant isolates. Detection of dfrA was highly sensitive (93.6%) and specific (91.4%) in predicting phenotypic trimethoprim resistance among E. coli and Klebsiella spp. isolates. The dfrA genes analysed were detected using a culture-independent PCR method in 16/94 (17%) urine samples. Phenotypic trimethoprim resistance was apparent in isolates cultured from 15/16 (94%) dfrA-positive urine samples. There was a significant association (P < 0.0001) between the presence of dfrA and trimethoprim resistance in urine samples containing Gram-negative bacteria (Sensitivity = 75%; Specificity = 96.9%; PPV = 93.8%; NPV = 86.1%). CONCLUSIONS: This study demonstrates that molecular detection of dfrA genes is a good indicator of trimethoprim resistance without the need for culture and susceptibility testing.

A systematic review of interventions to reduce anticholinergic burden in older people with dementia in primary care.

OBJECTIVE: This systematic review aimed to assess the types and effectiveness of interventions that sought to reduce anticholinergic burden (ACB) in people with dementia (PwD) in primary care. METHODS: One trial registry and eight electronic databases were systematically searched to identify eligible English language studies from inception until December 2021. To be eligible for inclusion, studies had to be randomised controlled trials (RCTs) or non-randomised studies (NRS), including controlled before-and-after studies and interrupted time-series studies, of interventions to reduce ACB in PwD aged ≥65 years (either community-dwelling or care home residents). All outcomes were to be considered. Quality was to be assessed using the Cochrane Risk of Bias tool for RCTs and ROBINS-I tool for NRS. If data could not be pooled for meta-analysis, a narrative synthesis was to be conducted. RESULTS: In total, 1880 records were found, with 1594 records remaining after removal of duplicates. Following title/abstract screening, 13 full-text articles were assessed for eligibility. None of these studies met the inclusion criteria for this review. Reasons for exclusion were incorrect study design, ineligible study population, lack of focus on reducing ACB, and studies conducted outside the primary care setting. CONCLUSIONS: This 'empty' systematic review highlights the lack of interventions to reduce ACB in PwD within primary care, despite this being highlighted as a priority area for research in recent clinical guidance. Future research should focus on development and testing of interventions to reduce ACB in this patient population through high-quality clinical trials.

Exposure to Ranitidine and Risk of Bladder Cancer: A Nested Case-Control Study.

INTRODUCTION: Ranitidine has been shown to contain the carcinogen N-nitrosodimethylamine and increase urinary N-nitrosodimethylamine in humans. We investigated whether ranitidine use is associated with increased bladder cancer risk. METHODS: A nested case-control study was conducted within the Primary Care Clinical Informatics Unit Research database which contains general practice records from Scotland. Bladder cancer cases, diagnosed between 1999 and 2011, were identified and matched with up to 5 controls (based on age, sex, general practice, and date of registration). Ranitidine, other histamine-2 receptor agonists, and proton pump inhibitors were identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for comorbidities and smoking. RESULTS: There were 3,260 cases and 14,037 controls. There was evidence of an increased risk of bladder cancer in ranitidine users, compared with nonusers (fully adjusted OR = 1.22; 95% CI 1.06-1.40), which was more marked with use for over 3 years of ranitidine (fully adjusted OR = 1.43; 95% CI 1.05-1.94). By contrast, there was little evidence of any association between proton pump inhibitor use and bladder cancer risk based on any use (fully adjusted OR = 0.98; 95% CI 0.88-1.11) or over 3 years of use (fully adjusted OR = 0.98; 95% CI 0.80-1.20). DISCUSSION: In this large population-based study, the use of ranitidine particularly long-term use was associated with an increased risk of bladder cancer. Further studies are necessary to attempt to replicate this finding in other settings.

'I just take them because I know the people that give them to me': A theory-informed interview study of community-dwelling people with dementia and carers' perspectives of medicines management.

OBJECTIVE: Identify facilitators and barriers to successful medicines management for people with dementia (PwD) in primary care from the perspectives of community-dwelling PwD and carers. METHODS: Semi-structured interviews conducted with PwD and carers in Northern Ireland. The 14-domain Theoretical Domains Framework guided data collection and analysis. Interviews explored participants' experiences and perceptions of medicines management. PwD also completed the Beliefs about Medicines Questionnaire indicating their level of agreement with statements about medicines. Qualitative data were analysed using the framework method and content analysis. Quantitative data were analysed descriptively. RESULTS: Eighteen PwD and 15 carers were interviewed. PwD believed they were competent with medicines management ('beliefs about capabilities'). Most PwD reported having strategies to prompt them to take their medicines ('memory, attention and decision processes'). Carers played an important role in supporting PwD with medicines management ('social influences') and monitoring adherence ('behavioural regulation') and anticipated having to take on a greater role as patients' cognitive impairment worsened ('beliefs about consequences'). Participants highlighted assistance provided by community pharmacies with medicines acquisition and delivery ('environmental context and resources') and placed great trust in primary healthcare professionals ('social influences'). PwD had positive attitudes towards medication and believed strongly in the necessity of their medicines. CONCLUSIONS: This is the first study to use a theoretical approach to explore medicines management for community-dwelling PwD. The findings provide new insights into the critical role of carers in facilitating optimal medicines management and will inform future intervention development, in which carers' needs assessment and involvement will be key.

Potentially inappropriate prescribing in dementia, multi-morbidity and incidence of adverse health outcomes.

IMPORTANCE: treatment of dementia in individuals with comorbidities is complex, leading to potentially inappropriate prescribing (PIP). The impact of PIP in this population is unknown. OBJECTIVE: to estimate the rate of PIP and its effect on adverse health outcomes (AHO). DESIGN: retrospective cohort. SETTING: primary care electronic health records linked to hospital discharge data from England. SUBJECTS: 11,175 individuals with dementia aged over 65 years in 2016 and 43,463 age- and sex-matched controls. METHODS: Screening Tool of Older Persons' Prescriptions V2 defined PIP. Logistic regression tested associations with comorbidities at baseline, and survival analyses risk of incident AHO, adjusted for age, gender, deprivation and 14 comorbidities. RESULTS: the dementia group had increased risk of PIP (73% prevalence; odds ratio [OR]: 1.92; confidence interval [CI]: 83-103%; P < 0.01) after adjusting for comorbidities. Most frequent PIP criteria were related to anti-cholinergic drugs and therapeutic duplication. Risk of PIP was higher in patients also diagnosed with coronary-heart disease (odds OR: 2.17; CI: 1.91-2.46; P < 0.01), severe mental illness (OR: 2.09; CI: 1.62-2.70; P < 0.01); and depression (OR: 1.81; CI: 1.62-2.01; P < 0.01). During follow-up (1 year), PIP was associated with increased all-cause mortality (hazard ratio: 1.14; CI: 1.02-1.26; P < 0.02), skin ulcer and pressure sores (hazard ratio: 1.66; CI: 1.12-2.46; P < 0.01), falls (hazard ratio: 1.37; CI: 1.15-1.63; P < 0.01), anaemia (hazard ratio: 1.61; CI: 1.10-2.38; P < 0.02) and osteoporosis (hazard ratio: 1.62; CI: 1.02-2.57; P < 0.04). CONCLUSION: patients with dementia frequently receive PIPs, and those who do are more likely to experience AHO. These results highlight the need to optimise medication in dementia patients, especially those with comorbidities.

A systematic review of general practice-based pharmacists' services to optimize medicines management in older people with multimorbidity and polypharmacy.

BACKGROUND: Few studies have evaluated roles of general practice-based pharmacists (PBPs), particularly in optimizing medicines management for older people with both multimorbidity and polypharmacy. OBJECTIVE: To explore the types and effectiveness of services provided by PBPs, either alone or in collaboration with other primary health care professionals, that sought to optimize medicines management for older people with multimorbidity and polypharmacy. METHODS: Eight electronic databases and three trial registries were searched for studies published in English until April 2020. Inclusion criteria were randomized controlled trials, non-randomized controlled trials and controlled before-and-after studies of services delivered by PBPs in primary care/general practice, for patients aged ≥65 years with both multimorbidity and polypharmacy that focused on a number of outcomes. The Cochrane risk of bias tool for randomized trials (RoB 1) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) assessment tool were used for quality assessment. A narrative synthesis was conducted due to study heterogeneity. RESULTS: Seven studies met inclusion criteria. All included studies employed PBP-led medication review accompanied by recommendations agreed and implemented by general practitioners. Other patient-level and practice-level interventions were described in one study. The limited available evidence suggested that PBPs, in collaboration with other practice team members, had mixed effects on outcomes focused on optimizing medicines management for older people. Most included studies were of poor quality and data to estimate the risk of bias were often missing. CONCLUSION: Future high-quality studies are needed to test the effects of PBP interventions on a well-defined range of medicines management-related outcomes.

Optimizing medicines use for older people (aged ≥ 65 years) with multimorbidity (the presence of two or more long-term conditions) and polypharmacy (the concomitant use of four or more medicines) is urgent due to an ageing population which commonly has complex medications regimens. It is anticipated that pharmacists who have been integrated into general practices [also called practice-based pharmacists (PBPs)] will positively impact on patient outcomes through various roles and activities. As the role of PBPs is relatively new, little is known about the exact nature of their role and how these pharmacists will optimize medicines management for older people in a patient-centred manner. The aim of this research was to provide a detailed understanding of how PBPs may enhance optimization of medication management in older people and to study the effects of PBPs' interventions on outcomes-focused on optimizing medicines management for older people with multimorbidity and polypharmacy such as quality of life. The seven included studies indicated that PBP-led interventions such as medication reviews improved a number of outcomes but had either a limited effect or no effect on other outcomes. Further high-quality research is needed in this area.

Process evaluation for the Care Homes Independent Pharmacist Prescriber Study (CHIPPS).

BACKGROUND: Medicines management in care homes requires significant improvement. CHIPPS was a cluster randomised controlled trial to determine the effectiveness of integrating pharmacist independent prescribers into care homes to assume central responsibility for medicines management. This paper reports the parallel mixed-methods process evaluation. METHOD: Intervention arm consisted of 25 triads: Care homes (staff and up to 24 residents), General Practitioner (GP) and Pharmacist Independent Prescriber (PIP). Data sources were pharmaceutical care plans (PCPs), pharmacist activity logs, online questionnaires and semi-structured interviews. Quantitative data were analysed descriptively. Qualitative data were analysed thematically. Results were mapped to the process evaluation objectives following the Medical Research Council framework. RESULTS: PCPs and activity logs were available from 22 PIPs. Questionnaires were returned by 16 PIPs, eight GPs, and two care home managers. Interviews were completed with 14 PIPs, eight GPs, nine care home managers, six care home staff, and one resident. All stakeholders reported some benefits from PIPs having responsibility for medicine management and identified no safety concerns. PIPs reported an increase in their knowledge and identified the value of having time to engage with care home staff and residents during reviews. The research paperwork was identified as least useful by many PIPs. PIPs conducted medication reviews on residents, recording 566 clinical interventions, many involving deprescribing; 93.8% of changes were sustained at 6 months. For 284 (50.2%) residents a medicine was stopped, and for a quarter of residents, changes involved a medicine linked to increased falls risk. Qualitative data indicated participants noted increased medication safety and improved resident quality of life. Contextual barriers to implementation were apparent in the few triads where PIP was not known previously to the GP and care home before the trial. In three triads, PIPs did not deliver the intervention. CONCLUSIONS: The intervention was generally implemented as intended, and well-received by most stakeholders. Whilst there was widespread deprescribing, contextual factors effected opportunity for PIP engagement in care homes. Implementation was most effective when communication pathways between PIP and GP had been previously well-established. TRIAL REGISTRATION: The definitive RCT was registered with the ISRCTN registry (registration number  ISRCTN 17847169 ).

Does potentially inappropriate prescribing predict an increased risk of admission to hospital and mortality? A longitudinal study of the 'oldest old'.

BACKGROUND: Potentially inappropriate prescribing (PIP) is associated with negative health outcomes, including hospitalisation and mortality. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is a longitudinal study of Maori (the indigenous population of New Zealand) and non-Maori octogenarians. Health disparities between indigenous and non-indigenous populations are prevalent internationally and engagement of indigenous populations in health research is necessary to understand and address these disparities. Using LiLACS NZ data, this study reports the association of PIP with hospitalisations and mortality prospectively over 36-months follow-up. METHODS: PIP, from pharmacist applied criteria, was reported as potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs). The association between PIP and hospitalisations (all-cause, cardiovascular disease-specific and ambulatory-sensitive) and mortality was determined throughout a series of 12-month follow-ups using binary logistic (hospitalisations) and Cox (mortality) regression analysis, reported as odds ratios (ORs) and hazard ratios (HRs), respectively, and the corresponding confidence intervals (CIs). RESULTS: Full demographic data were obtained for 267 Maori and 404 non-Maori at baseline, 178 Maori and 332 non-Maori at 12-months, and 122 Maori and 281 non-Maori at 24-months. The prevalence of any PIP (i.e. ≥1 PIM and/or PPO) was 66, 75 and 72% for Maori at baseline, 12-months and 24-months, respectively. In non-Maori, the prevalence of any PIP was 62, 71 and 73% at baseline, 12-months and 24-months, respectively. At each time-point, there were more PPOs than PIMs; at baseline Maori were exposed to a significantly greater proportion of PPOs compared to non-Maori (p = 0.02). In Maori: PPOs were associated with a 1.5-fold increase in hospitalisations and mortality. In non-Maori, PIMs were associated with a double risk of mortality. CONCLUSIONS: PIP was associated with an increased risk of hospitalisation and mortality in this cohort. Omissions appear more important for Maori in predicting hospitalisations, and PIMs were more important in non-Maori in predicting mortality. These results suggest understanding prescribing outcomes across and between population groups is needed and emphasises prescribing quality assessment is useful.

Improving medicines management for people with dementia in primary care: a qualitative study of healthcare professionals to develop a theory-informed intervention.

BACKGROUND: People with dementia (PwD) face unique challenges with medicines management, yet little is known about these challenges from the perspectives of primary healthcare professionals, particularly general practitioners (GPs) and community pharmacists. Few medicines management interventions have been developed which are aimed at community-dwelling PwD. This study sought to develop an intervention to improve medicines management for PwD in primary care using a theory-informed approach. METHODS: Semi-structured interviews were conducted with GPs (n = 15) and community pharmacists (n = 15) to explore participants' views and experiences of medicines management for PwD, and their perceptions of barriers and facilitators to successful medicines management for PwD. The 14-domain Theoretical Domains Framework was the underpinning theoretical guide, allowing key theoretical domains to be identified and mapped to behaviour change techniques (BCTs) which are considered the 'active ingredients' of an intervention. Draft interventions were developed to operationalise selected BCTs and were presented to GPs and community pharmacists during task groups. Final selection of an intervention for feasibility testing was guided by feedback provided during these task groups and through application of the APEASE (Affordability, Practicability, Effectiveness/cost-effectiveness, Acceptability, Side-effects/safety, Equity) criteria. RESULTS: Participants expressed a number of concerns about medicines management for PwD, particularly monitoring adherence to medication regimens and conducting medication review. Two draft interventions comprising selected BCTs ('Modelling or demonstration of behaviour'; 'Salience of consequences'; 'Health consequences'; 'Social and environmental consequences'; 'Action planning'; Social support or encouragement', 'Self-monitoring of behaviour') were developed, each targeting GPs and community pharmacists. Following the task groups and discussions within the research team, the community pharmacy-based intervention was selected for future feasibility testing. The intervention will target community pharmacists to conduct a medication review (incorporating an adherence check) with a PwD, delivered as an online video demonstrating key behaviours. The video will include feedback emphasising positive outcomes of performing the behaviours. Action planning and a quick reference guide will be used as complementary intervention components. CONCLUSIONS: A community pharmacist-based intervention has been developed targeting medicines management for PwD in primary care using a systematic, theory-informed approach. Future work will determine the usability and acceptability of implementing this intervention in clinical practice.

Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer.

BACKGROUND & AIMS: Preclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer. METHODS: We performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts. RESULTS: The combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32). CONCLUSIONS: In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

Statin use and survival in patients with gastric cancer in two independent population-based cohorts.

PURPOSE: Preclinical studies show statins inhibit pathways involved in gastric cancer progression, with observational studies demonstrating reduced gastric cancer risk in statin users. However, few studies have investigated statin use and survival in gastric cancer. We investigated statin use and survival in two large population-based gastric cancer cohorts. METHODS: Patients diagnosed with gastric cancer from 1998 to 2012 were identified from English and Scottish cancer registries. Statin prescriptions were identified from linkages to the UK Clinical Practice Research Datalink in England and the Prescribing Information System in Scotland, and deaths identified from national mortality records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use in multivariate analysis. Meta-analysis techniques pooled results across the cohorts. RESULTS: The combined cohorts contained 3833 patients with gastric cancer and 2392 cancer-specific deaths. Statin use after diagnosis was associated with reduced cancer-specific mortality (adjusted HR 0.83; 95% CI, 0.74-0.92). HRs for less than 1 year and over 1 year of statin use were similar (adjusted HR 0.83; 95% CI, 0.73-0.94 and adjusted HR 0.83; 95% CI, 0.64-1.01, respectively). Statin use prior to diagnosis was also associated with reduced cancer-specific mortality (adjusted HR 0.91; 95% CI, 0.84-0.98). CONCLUSIONS: In two independent UK cohorts, there was some evidence that statin use was associated with reduced cancer-specific mortality. However, these associations were weak in magnitude and did not follow a clear dose response, and we cannot rule out confounding by stage.

The development of a Core Outcome Set for medicines management interventions for people with dementia in primary care.

BACKGROUND: people with dementia (PWD), and their carers, face challenges with medicines management activities. As interventions to support medicines management for PWD are developed, consideration must be given to the outcomes chosen to measure their effectiveness. A Core Outcome Set (COS) is a minimum set of outcomes to be measured in all trials in a particular clinical area, which seeks to reduce heterogeneity of outcome reporting across trials. OBJECTIVE: to develop a COS for trials assessing the effectiveness of medicines management interventions for PWD in primary care. METHODS: a comprehensive list of outcomes was compiled through a systematic review and semi-structured interviews with PWD (n = 18), their carers (n = 15), community pharmacists (n = 15) and general practitioners (n = 15). These outcomes were rated by a Delphi panel (n = 52) on a nine-point Likert scale from 1 (limited importance) to 9 (critical) during three sequential rounds of questionnaire distribution. The Delphi panel comprised participants with expertise in dementia and medicines management, including academics and healthcare professionals. An outcome was eligible for inclusion in the COS if ≥70% of participants rated it critical and <15% of participants rated it of limited importance. RESULTS: twenty-nine outcomes identified from the systematic review and stakeholder interviews were presented to the Delphi panel. Consensus was reached on 21 outcomes, of which the 7 most highly rated were recommended for inclusion in the COS. CONCLUSION: this study used robust methodology to develop a COS for medicines management interventions for PWD. Future work should identify the most appropriate tools to measure these outcomes.

Improving adherence to multiple medications in older people in primary care: Selecting intervention components to address patient-reported barriers and facilitators.

BACKGROUND: Medication adherence is vital to ensuring optimal patient outcomes, particularly amongst multimorbid older people prescribed multiple medications. Interventions targeting adherence often lack a theoretical underpinning and this may impact on effectiveness. The theoretical domains framework (TDF) of behaviour can aid intervention development by systematically identifying key determinants of medication adherence. OBJECTIVES: This study aimed to (i) identify determinants (barriers, facilitators) of adherence to multiple medications from older people's perspectives; (ii) identify key domains to target for behaviour change; and (iii) map key domains to intervention components [behaviour change techniques (BCTs)] that could be delivered in an intervention by community pharmacists. METHOD: Focus groups were conducted with older people (>65 years) receiving ≥4 medications. Questions explored the 12 domains of the TDF (eg "Knowledge," "Emotion"). Data were analysed using the framework method and content analysis. Identification of key domains and mapping to intervention components (BCTs) followed established methods. RESULTS: Seven focus groups were convened (50 participants). A wide range of determinants were identified as barriers (eg forgetfulness, prioritization of medications) and facilitators (eg social support, personalized routines) of adherence to multiple medications. Eight domains were identified as key targets for behaviour change (eg "Social influences," "Memory, attention and decision processes," "Motivation and goals") and mapped to 11 intervention components (BCTs) to include in an intervention [eg "Social support or encouragement (general)," "Self-monitoring of the behaviour," "Goal-setting (behaviour)"]. CONCLUSION: This study used a theoretical underpinning to identify potential intervention components (BCTs). Future work will incorporate the selected BCTs into an intervention that will undergo feasibility testing in community pharmacies.

REDUCING POTENTIALLY INAPPROPRIATE PRESCRIBING FOR OLDER PEOPLE IN PRIMARY CARE: COST-EFFECTIVENESS OF THE OPTI-SCRIPT INTERVENTION.

OBJECTIVES: This study examines the cost-effectiveness of the OPTI-SCRIPT intervention on potentially inappropriate prescribing in primary care. METHODS: Economic evaluation, using incremental cost-effectiveness and cost utility analyses, conducted alongside a cluster randomized controlled trial of twenty-one general practices and 196 patients, to compare a multifaceted intervention with usual practice in primary care in Ireland. Potentially inappropriate prescriptions (PIPs) were determined by a pharmacist. Incremental costs, PIPs, and quality-adjusted life-years (QALYs) at 12-month follow-up were estimated using multilevel regression. Uncertainty was explored using cost-effectiveness acceptability curves. RESULTS: The intervention was associated with a nonsignificant mean cost increase of €407 (95 percent CIs, -357-1170), a significant mean reduction in PIPs of 0.379 (95 percent CI, 0.092-0.666), and a nonsignificant mean increase in QALYs of 0.013 (95 percent CIs, -0.016-0.042). The incremental cost per PIP avoided was €1,269 (95 percent CI, -1400-6302) and the incremental cost per QALY gained was €30,535 (95 percent CI, -334,846-289,498). The probability of the intervention being cost-effective was 0.602 at a threshold value of €45,000 per QALY gained and was at least 0.845 at threshold values of €2,500 per PIP avoided and higher. CONCLUSIONS: While the OPTI-SCRIPT intervention was effective in reducing potentially inappropriate prescribing in primary care in Ireland, our findings highlight the uncertainty with respect to its cost-effectiveness. Further studies are required to explore the health and economic implications of interventions targeting potentially inappropriate prescribing.

Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

Statin use and breast cancer survival: a nationwide cohort study in Scotland.

BACKGROUND: Preclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality. METHODS: We conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin. RESULTS: A total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose-response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98). CONCLUSION: Overall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer.