Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care.

INTRODUCTION: After puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external factors. AIM: To evaluate the sex differences in the characteristics and treatment of patients with severe asthma (SA) in a real-world setting. METHODS: Demographic, clinical and treatment characteristics for patients with SA in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD) were retrospectively analysed by sex using univariable and multivariable logistic regression analyses adjusted for year, age and hospital/practice. RESULTS: 3679 (60.9% female) patients from UKSAR and 18 369 patients (67.9% female) from OPCRD with SA were included. Females were more likely to be symptomatic with increased Asthma Control Questionnaire-6 (UKSAR adjusted OR (aOR) 1.14, 95% CI 1.09 to 1.18) and Royal College of Physicians-3 Question scores (OPCRD aOR 1.29, 95% CI 1.13 to 1.47). However, they had a higher forced expiratory volume in 1 second per cent (FEV1%) predicted (UKSAR 68.7% vs 64.8%, p<0.001) with no significant difference in peak expiratory flow. Type 2 biomarkers IgE (UKSAR 129 IU/mL vs 208 IU/mL, p<0.001) and FeNO (UKSAR 36ppb vs 46ppb, p<0.001) were lower in females with no significant difference in blood eosinophils or biological therapy. Females were less likely to be on maintenance oral corticosteroids (UKSAR aOR 0.86, 95% CI 0.75 to 0.99) but more likely to be obese (UKSAR aOR 1.67, 95% CI 145 to 1.93; OPCRD SA aOR 1.46, 95% CI 1.34 to 1.58). CONCLUSIONS: Females had increased symptoms and were more likely to be obese despite higher FEV1% predicted and lower type 2 biomarkers with consistent and clinically important differences across both datasets.

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.

Oral antibiotic use and early-onset colorectal cancer: findings from a case-control study using a national clinical database.

BACKGROUND: Antibiotic-induced gut dysbiosis has been associated with colorectal cancer (CRC) in older adults. This study will investigate whether an association exists between antibiotic usage and early-onset colorectal cancer (CRC), and also evaluate this in later-onset CRC for comparison. METHODS: A case-control study was conducted using primary care data from 1999-2011. Analysis were conducted separately in early-onset CRC cases (diagnosed < 50 years) and later-onset cases (diagnosed ≥ 50 years). Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CI) for the associations between antibiotic exposure and CRC by tumour location, adjusting for comorbidities. RESULTS: Seven thousands nine hundred and three CRC cases (445 aged <50 years) and 30,418 controls were identified. Antibiotic consumption was associated with colon cancer in both age-groups, particularly in the early-onset CRC cohort (<50 years: adjusted Odds Ratio (ORadj) 1.49 (95% CI 1.07, 2.07), p = 0·018; ≥50 years (ORadj (95% CI) 1.09 (1.01, 1.18), p = 0·029). Antibiotics were not associated with rectal cancer (<50 years: ORadj (95% CI) 1.17 (0.75, 1.84), p = 0.493; ≥50 years: ORadj (95% CI) 1.07 (0.96, 1.19), p = 0.238). CONCLUSION: Our findings suggest antibiotics may have a role in colon tumour formation across all age-groups.

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.

Determinants of intentions to monitor antihypertensive medication adherence in Irish community pharmacy: a factorial survey.

BACKGROUND: Community pharmacy represents an important setting to identify patients who may benefit from an adherence intervention, however it remains unclear whether it would be feasible to monitor antihypertensive adherence within the workflow of community pharmacy. The aim of this study was to identify facilitators and barriers to monitoring antihypertensive medication adherence of older adults at the point of repeat dispensing. METHODS: We undertook a factorial survey of Irish community pharmacists, guided by a conceptual model adapted from the Theory of Planned Behaviour (TPB). Respondents completed four sections, 1) five factorial vignettes (clinical scenario of repeat dispensing), 2) a medication monitoring attitude measure, 3) subjective norms and self-efficacy questions, and 4) demographic and workplace questions. Barriers and facilitators to adherence monitoring behaviour were identified in factorial vignette analysis using multivariate multilevel linear modelling, testing the effect of both contextual factors embedded within the vignettes (section 1), and respondent-level factors (sections 2-4) on likelihood to perform three adherence monitoring behaviours in response to the vignettes. RESULTS: Survey invites (n = 1543) were sent via email and 258 completed online survey responses were received; two-thirds of respondents were women, and one-third were qualified pharmacists for at least 15 years. In factorial vignette analysis, pharmacists were more inclined to monitor antihypertensive medication adherence by examining refill-patterns from pharmacy records than asking patients questions about their adherence or medication beliefs. Pharmacists with more positive attitudes towards medication monitoring and normative beliefs that other pharmacists monitored adherence, were more likely to monitor adherence. Contextual factors also influenced pharmacists' likelihood to perform the three adherence monitoring behaviours, including time-pressures and the number of days late the patient collected their repeat prescription. Pharmacists' normative beliefs and the number of days late the patient collected their repeat prescription had the largest quantitative influence on responses. CONCLUSIONS: This survey identified that positive pharmacist attitudes and normative beliefs can facilitate adherence monitoring within the current workflow; however contextual time-barriers may prevent adherence monitoring. Future research should consider these findings when designing a pharmacist-led adherence intervention to be integrated within current pharmacy workflow.

Developing outcome, process and balancing measures for an emergency department longitudinal patient monitoring system using a modified Delphi.

BACKGROUND: Early warning score systems have been widely recommended for use to detect clinical deterioration in patients. The Irish National Emergency Medicine Programme has developed and piloted an emergency department specific early warning score system. The objective of this study was to develop a consensus among frontline healthcare staff, quality and safety staff and health systems researchers regarding evaluation measures for an early warning score system in the Emergency Department. METHODS: Participatory action research including a modified Delphi consensus building technique with frontline hospital staff, quality and safety staff, health systems researchers, local and national emergency medicine stakeholders was the method employed in this study. In Stage One, a workshop was held with the participatory action research team including frontline hospital staff, quality and safety staff and health systems researchers to gather suggestions regarding the evaluation measures. In Stage Two, an electronic modified-Delphi study was undertaken with a panel consisting of the workshop participants, key local and national emergency medicine stakeholders. Descriptive statistics were used to summarise the characteristics of the panellists who completed the questionnaires in each round. The mean Likert rating, standard deviation and 95% bias-corrected bootstrapped confidence interval for each variable was calculated. Bonferroni corrections were applied to take account of multiple testing. Data were analysed using Stata 14.0 SE. RESULTS: Using the Institute for Healthcare Improvement framework, 12 process, outcome and balancing metrics for measuring the effectiveness of an ED-specific early warning score system were developed. CONCLUSION: There are currently no published measures for evaluating the effectiveness of an ED early warning score system. It was possible in this study to develop a suite of evaluation measures using a modified Delphi consensus approach. Using the collective expertise of frontline hospital staff, quality and safety staff and health systems researchers to develop and categorise the initial set of potential measures was an innovative and unique element of this study.

External validation of the Vulnerable Elder's Survey for predicting mortality and emergency admission in older community-dwelling people: a prospective cohort study.

BACKGROUND: Prospective external validation of the Vulnerable Elder's Survey (VES-13) in primary care remains limited. The aim of this study is to externally validate the VES-13 in predicting mortality and emergency admission in older community-dwelling adults. METHODS: Design: Prospective cohort study with 2 years follow-up (2010-2012). SETTING: 15 General Practices (GPs) in the Republic of Ireland. PARTICIPANTS: n = 862, aged ≥70 years, community-dwellers Exposure: VES-13 calculated at baseline, where a score of ≥3 denoted high risk. OUTCOMES: i) Mortality; ii) ≥1 Emergency admission and ≥1 ambulatory care sensitive (ACS) admission over 2 years. STATISTICAL ANALYSIS: Descriptive statistics, model discrimination (c-statistic) and sensitivity/specificity. RESULTS: Of 862 study participants, a total of 246 (38%) were classified as vulnerable at baseline. Fifty-three (6%) died during follow-up and 246 (29%) had an emergency admission. At the VES-13 cut-point of ≥3 denoting high-risk model discrimination was poor for mortality (c-statistic: 0.61 (95% CI 0.54, 0.67), ≥1 emergency admission (c-statistic: 0.59 (95% CI 0.56, 0.63) and ≥1 ACS emergency admission (c-statistic: 0.63 (95% CI 0.60, 0.67). CONCLUSIONS: In this study the VES-13 demonstrated relatively limited predictive accuracy in predicting mortality and emergency admission. External validation studies examining the tool in different health settings and healthier populations are needed and represent an interesting area for future research.

GPs' and community pharmacists' opinions on medication management at transitions of care in Ireland.

OBJECTIVE: The aim of this study was to survey GPs and community pharmacists (CPs) in Ireland regarding current practices of medication management, specifically medication reconciliation, communication between health care providers and medication errors as patients transition in care. METHODS: A national cross-sectional survey was distributed electronically to 2364 GPs, 311 GP Registrars and 2382 CPs. Multivariable associations comparing GPs to CPs were generated and content analysis of free text responses was undertaken. RESULTS: There was an overall response rate of 17.7% (897 respondents-554 GPs/Registrars and 343 CPs). More than 90% of GPs and CPs were positive about the effects of medication reconciliation on medication safety and adherence. Sixty per cent of GPs reported having no formal system of medication reconciliation. Communication between GPs and CPs was identified as good/very good by >90% of GPs and CPs. The majority (>80%) of both groups could clearly recall prescribing errors, following a transition of care, they had witnessed in the previous 6 months. Free text content analysis corroborated the positive relationship between GPs and CPs, a frustration with secondary care communication, with many examples given of prescribing errors. CONCLUSIONS: While there is enthusiasm for the benefits of medication reconciliation there are limited formal structures in primary care to support it. Challenges in relation to systems that support inter-professional communication and reduce medication errors are features of the primary/secondary care transition. There is a need for an improved medication management system. Future research should focus on the identified barriers in implementing medication reconciliation and systems that can improve it.

Oral prednisolone and warfarin and risk of oesophageal cancer: A case-control study.

BACKGROUND: A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. METHODS: A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. RESULTS: There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). CONCLUSIONS: In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.

An examination of factorial invariance of the Asthma Control Questionnaire among adults with severe asthma.

BACKGROUND: The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown. METHODS: Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed. RESULTS: A one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p<0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p<0.01)and increased with age (p<0.01). Reliability of the instrument was high (over 88%) in all subgroups studied. CONCLUSION: The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.

Prescriber Variation in Relation to Prescribing Trends within the Preferred Drugs Initiative in Ireland (2012-2015): An Interrupted Time-Series Study Using Latent Curve Models.

OBJECTIVES: To examine the impact of the Preferred Drugs Initiative (PDI), an Irish health policy aimed at reducing prescribing variation. DESIGN: Interrupted time series spanning 2012 to 2015. SETTING: Health Service Executive pharmacy claims data for General Medical Services (GMS) patients, approximately 40% of the Irish population. PARTICIPANTS: Prescribers issuing preferred drug group items to GMS adults before and after PDI guidelines. PRIMARY OUTCOME: The percentage coverage of PDI medications within each drug class per calendar quarter per prescriber. METHODS: Latent curve models with structured residuals (LCM-SRs) were used to model coverage of the preferred drugs over time. The number of GMS adults receiving medication and the percentage who were 65 years and older at the start of the study were included as covariates. RESULTS: In the quarter following PDI guidelines, coverage of the preferred drugs increased most in absolute terms for proton pump inhibitors (PPIs) (1.50% [SE 0.15], P < 0.001) and selective and norepinephrine reuptake inhibitors (SNRIs) (1.17% [SE 0.26], P < 0.001). Variation between prescribers remained relatively unchanged and increased for urology medications. Prescribers who increased coverage of the preferred PPI also increased coverage of the preferred statin immediately following guidelines (correlation 0.47 [SE 0.13], P < 0.001). Where guidelines were disseminated simultaneously, coverage of one preferred drug did not significantly predict coverage of the other preferred drug in the next calendar quarter. Prescribing of preferred drugs was not moderated by prescriber-level factors. CONCLUSIONS: Modest changes in prescribing of the preferred drugs have been observed over the course of the PDI. However, the guidelines have had little impact in reducing variation between prescribers. Further strategies may be necessary to reduce variation in clinical practice and enhance patient care.

Predicting poorer health outcomes in older community-dwelling patients with multimorbidity: prospective cohort study assessing the accuracy of different multimorbidity definitions.

PURPOSE: Multimorbidity is commonly defined and measured using condition counts. The UK National Institute for Health Care Excellence Guidelines for Multimorbidity suggest that a medication-orientated approach could be used to identify those in need of a multimorbidity approach to management. OBJECTIVES: To compare the accuracy of medication-based and diagnosis-based multimorbidity measures at higher cut-points to identify older community-dwelling patients who are at risk of poorer health outcomes. DESIGN: A secondary analysis of a prospective cohort study with a 2-year follow-up (2010-2012). SETTING: 15 general practices in Ireland. PARTICIPANTS: 904 older community-dwelling patients. EXPOSURE: Baseline multimorbidity measurements based on both medication classes count (MCC) and chronic disease count (CDC). OUTCOMES: Mortality, self-reported health related quality of life, mental health and physical functioning at follow-up. ANALYSIS: Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) adjusting for clustering by practice for each outcome using both definitions. RESULTS: Of the 904 baseline participants, 53 died during follow-up and 673 patients completed the follow-up questionnaire. At baseline, 223 patients had 3 or more chronic conditions and 89 patients were prescribed 10 or more medication classes. Sensitivity was low for both MCC and CDC measures for all outcomes. For specificity, MCC was better for all outcomes with estimates varying from 88.8% (95% CI 85.2% to 91.6%) for physical functioning to 90.9% (95% CI 86.2% to 94.1%) for self-reported health-related quality of life. There were no differences between MCC and CDC in terms of PPV and NPV for any outcomes. CONCLUSIONS: Neither measure demonstrated high sensitivity. However, MCC using a definition of 10 or more regular medication classes to define multimorbidity had higher specificity for predicting poorer health outcomes. While having limitations, this definition could be used for proactive identification of patients who may benefit from targeted clinical care.

Unintended discontinuation of medication following hospitalisation: a retrospective cohort study.

OBJECTIVES: Whether unintended discontinuation of common, evidence-based, long-term medication occurs after hospitalisation; what factors are associated with unintended discontinuation; and whether the presence of documentation of medication at hospital discharge is associated with continuity of medication in general practice. DESIGN: Retrospective cohort study between 2012 and 2015. SETTING: Electronic records and hospital supplied discharge notifications in 44 Irish general practices. PARTICIPANTS: 20 488 patients aged 65 years or more prescribed long-term medication for chronic conditions. PRIMARY AND SECONDARY OUTCOMES: Discontinuity of four evidence-based medication drug classes: antithrombotic, lipid-lowering, thyroid replacement drugs and respiratory inhalers in hospitalised versus non-hospitalised patients; patient and health system factors associated with discontinuity; impact of the presence of medication in the hospital discharge summary on continuity of medication in a patient's general practitioner (GP) prescribing record at 6 months follow-up. RESULTS: In patients admitted to hospital, medication discontinuity ranged from 6%-11% in the 6 months posthospitalisation. Discontinuity of medication is significantly lower for hospitalised patients taking respiratory inhalers (adjusted OR (AOR) 0.63, 95% CI (0.49 to 0.80), p<0.001) and thyroid medications (AOR 0.62, 95% CI (0.40 to 0.96), p=0.03). There is no association between discontinuity of medication and hospitalisation for antithrombotics (AOR 0.95, 95% CI (0.81 to 1.11), p=0.49) or lipid lowering medications (AOR 0.92, 95% CI (0.78 to 1.08), p=0.29). Older patients and those who paid to see their GP were more likely to experience increased odds of discontinuity in all four medicine groups. Less than half (39% to 47.4%) of patients had medication listed on their hospital discharge summary. Presence of medication on hospital discharge summary is significantly associated with continuity of medication in the GP prescribing record for lipid lowering medications (AOR 1.64, 95% CI (1.15 to 2.36), p=0.01) and respiratory inhalers (AOR 2.97, 95% CI (1.68 to 5.25), p<0.01). CONCLUSION: Discontinuity of evidence-based long-term medication is common. Increasing age and private medical care are independently associated with a higher risk of medication discontinuity. Hospitalisation is not associated with discontinuity but less than half of hospitalised patients have medication recorded on their hospital discharge summary.

Prescribing Variation in General Practices in England Following a Direct Healthcare Professional Communication on Mirabegron.

INTRODUCTION: Pharmacovigilance may detect safety issues after marketing of medications, and this can result in regulatory action such as direct healthcare professional communications (DHPC). DHPC can be effective in changing prescribing behaviour, however the extent to which prescribers vary in their response to DHPC is unknown. This study aims to explore changes in prescribing and prescribing variation among general practitioner (GP) practices following a DHPC on the safety of mirabegron, a medication to treat overactive bladder (OAB). METHODS: This is an interrupted time series study of English GP practices from 2014⁻2017. National Health Service (NHS) Digital provided monthly statistics on aggregate practice-level prescribing and practice characteristics (practice staff and registered patient profiles, Quality and Outcomes Framework indicators, and deprivation of the practice area). The primary outcome was monthly mirabegron prescriptions as a percentage of all OAB drug prescriptions and we assessed the change following a DHPC issued by the European Medicines Agency in September 2015. The DHPC stated mirabegron use was contraindicated with severe uncontrolled hypertension and cautioned with hypertension. Variation between practices in mirabegron prescribing before and after the DHPC was assessed using the systematic component of variation (SCV). Multilevel segmented regression with random effects quantified the change in level and trend of prescribing after the DHPC. Practice characteristics were assessed for their association with a reduction in prescribing following the DHPC. RESULTS: This study included 7408 practices. During September 2015, 88.9% of practices prescribed mirabegron and mirabegron comprised a mean of 8.2% (SD 6.8) of OAB prescriptions. Variation between practices was classified as very high and the median SCV did not change significantly (p = 0.11) in the six months after the September 2015 DHPC (12.4) compared to before (11.6). Before the DHPC, the share of mirabegron over all OAB drug prescriptions increased by 0.294 (95% confidence interval (CI), 0.287, 0.301) percentage points per month. There was no significant change in the month immediately after the DHPC (-0.023, 95% CI -0.105 to 0.058), however there was a significant reduction in trend (-0.036, 95% CI -0.049 to -0.023). Higher numbers of registered patients, patients aged ≥65 years, and practice area deprivation were associated with having a significant decrease in level and slope of mirabegron prescribing post-DHPC. CONCLUSION: Variation in mirabegron prescribing was high over the study period and did not change substantively following the DHPC. There was no immediate prescribing change post-DHPC, although the monthly growth did slow. Knowledge of the degree of variation in and determinants of response to safety communications may allow those that do not change prescribing habits to be provided with additional support.

Prevalence of potentially inappropriate prescribing in older people in primary care and its association with hospital admission: longitudinal study.

OBJECTIVE: To determine whether hospital admission is associated with potentially inappropriate prescribing among older primary care patients (aged ≥65 years) and whether such prescribing was more likely after hospital admission than before. DESIGN: Longitudinal study of retrospectively extracted data from general practice records. SETTING: 44 general practices in Ireland in 2012-15. PARTICIPANTS: Adults aged 65 years or over attending participating practices. EXPOSURE: Admission to hospital (any hospital admission versus none, and post-admission versus pre-admission). MAIN OUTCOME MEASURES: Prevalence of potentially inappropriate prescribing assessed using 45 criteria from the Screening Tool for Older Persons' Prescription (STOPP) version 2, analysed both as rate of distinct potentially inappropriate prescribing criteria met (stratified Cox regression) and binary presence of potentially inappropriate prescribing (logistic regression) and adjusted for patients' characteristics. A sensitivity analysis used matching with propensity scores based on patients' characteristics and diagnoses. RESULTS: Overall 38 229 patients were included, and during 2012 the mean age was 76.8 (SD 8.2) years and 43% (13 212) were male. Each year, 10.4-15.0% (3015/29 077 in 2015 to 4537/30 231 in 2014) of patients had at least one hospital admission. The overall prevalence of potentially inappropriate prescribing ranged from 45.3% (13 940/30 789) of patients in 2012 to 51.0% (14 823/29 077) in 2015. Independently of age, sex, number of prescription items, comorbidity, and health cover, hospital admission was associated with a higher rate of distinct potentially inappropriate prescribing criteria met; the adjusted hazard ratio for hospital admission was 1.24 (95% confidence interval 1.20 to 1.28). Among participants who were admitted to hospital, the likelihood of potentially inappropriate prescribing after admission was higher than before admission, independent of patients' characteristics; the adjusted odds ratio for after hospital admission was 1.72 (1.63 to 1.84). Analysis of propensity score matched pairs showed a slight reduction in the hazard ratio for hospital admission to 1.22 (1.18 to 1.25). CONCLUSION: Hospital admission was independently associated with potentially inappropriate prescribing. It is important to determine how hospital admission may affect appropriateness of prescribing for older people and how potential adverse consequences of admission can be minimised.

An evaluation of prescribing trends and patterns of claims within the Preferred Drugs Initiative in Ireland (2011-2016): an interrupted time-series study.

OBJECTIVE: To examine the impact of the Preferred Drugs Initiative (PDI), an Irish health policy aimed at enhancing evidence-based cost-effective prescribing, on prescribing trends and the cost of prescription medicines across seven medication classes. DESIGN: Retrospective repeated cross-sectional study spanning the years 2011-2016. SETTING: Health Service Executive Primary Care Reimbursement Service pharmacy claims data for General Medical Services (GMS) patients, approximately 40% of the Irish population. PARTICIPANTS: Adults aged ≥18 years between 2011 and 2016 are eligible for the GMS scheme. PRIMARY AND SECONDARY OUTCOMES: The percentage of PDI medications within each drug class per calendar quarter. Linear regression was used to model prescribing of the preferred drug within each medication group and to assess the impact of PDI guidelines and other relevant changes in prescribing practice. Savings in drug expenditure were estimated. RESULTS: Between 2011 and 2016, around a quarter (23.59%) of all medications were for single-agent drugs licensed in the seven drug classes. There was a small increase in the percentage of PDI drugs, increasing from 4.64% of all medications in 2011 to 4.76% in 2016 (P<0.001). The percentage of preferred drugs within each drug class was significantly higher immediately following publication of the guidelines for all classes except urology, with the largest increases noted for lansoprazole (1.21%, 95% CI: 0.84% to 1.57%, P<0.001) and venlafaxine (0.71%, 95% CI: 0.15% to 1.27%, P=0.02). Trends in prescribing of the preferred drugs between PDI guidelines and the end of 2016 varied between drug classes. Total cost savings between 2013 and 2016 were estimated to be €2.7 million. CONCLUSION: There has been a small increase in prescribing of PDI drugs in response to prescribing guidelines, with inconsistent changes observed across therapeutic classes. These findings are relevant where health services are seeking to develop more active prescribing interventions aimed at changing prescribing practice.

Quantifying patient preferences for symptomatic breast clinic referral: a decision analysis study.

OBJECTIVES: Decision analysis study that incorporates patient preferences and probability estimates to investigate the impact of women's preferences for referral or an alternative strategy of watchful waiting if faced with symptoms that could be due to breast cancer. SETTING: Community-based study. PARTICIPANTS: Asymptomatic women aged 30-60 years. INTERVENTIONS: Participants were presented with 11 health scenarios that represent the possible consequences of symptomatic breast problems. Participants were asked the risk of death that they were willing to take in order to avoid the health scenario using the standard gamble utility method. This process was repeated for all 11 health scenarios. Formal decision analysis for the preferred individual decision was then estimated for each participant. PRIMARY OUTCOME MEASURE: The preferred diagnostic strategy was either watchful waiting or referral to a breast clinic. Sensitivity analysis was used to examine how each varied according to changes in the probabilities of the health scenarios. RESULTS: A total of 35 participants completed the interviews, with a median age 41 years (IQR 35-47 years). The majority of the study sample was employed (n=32, 91.4%), with a third-level (university) education (n=32, 91.4%) and with knowledge of someone with breast cancer (n=30, 85.7%). When individual preferences were accounted for, 25 (71.4%) patients preferred watchful waiting to referral for triple assessment as their preferred initial diagnostic strategy. Sensitivity analysis shows that referral for triple assessment becomes the dominant strategy at the upper probability estimate (18%) of breast cancer in the community. CONCLUSIONS: Watchful waiting is an acceptable strategy for most women who present to their general practitioner (GP) with breast symptoms. These findings suggest that current referral guidelines should take more explicit account of women's preferences in relation to their GPs initial management strategy.

Impact of Potentially Inappropriate Prescribing on Adverse Drug Events, Health Related Quality of Life and Emergency Hospital Attendance in Older People Attending General Practice: A Prospective Cohort Study.

BACKGROUND: Potentially inappropriate prescribing (PIP) describes medications where risk generally outweighs benefit for older people. Cross-sectional studies suggest an association between PIP and poorer health outcomes but there is a paucity of prospective cohort studies. This study investigates the longitudinal association of PIP with adverse drug events (ADEs), health related quality of life, and accident & emergency visits. METHODS: Study design: Two-year (2010-2012) prospective cohort study (n = 904, ≥70 years, community-dwelling) with linked pharmacy dispensing data. EXPOSURE: Baseline PIP: Screening Tool for Older Persons potentially Inappropriate Prescriptions (STOPP) and Beers 2012 applied 12 months prior. STUDY OUTCOMES: ADEs (patient interview), health related quality of life (EQ-5D-3L: patient questionnaire), and accident & emergency visits (general practice medical record review). STATISTICAL ANALYSIS: Descriptive statistics: Poisson (incidence rate ratio [95% confidence interval [CI]], linear regression models [regression coefficient [95% CI]], and logistic [odds ratio [OR] [95% CI]). RESULTS: Of 791 participants eligible for follow-up, 673 (85%) returned a questionnaire and 605 (77%) also completed an ADE interview. Baseline STOPP PIP prevalence was 40% and 445 (74%) patients reported ≥1 ADE at follow-up. In multivariable analysis, ≥2 STOPP PIP was associated with ADEs (adjusted incidence rate ratio: 1.29 [95% CI 1.03, 1.85; p = .03]; poorer health related quality of life [adjusted regression coefficient: -0.11 [95% CI -0.16, -0.06; p < .001]]; and, ≥1 accident & emergency visit [adjusted OR: 1.85 [95% CI 1.06, 3.24; p = .03]]). Baseline Beers 2012 prevalence was 26% and there was no association with adverse health outcomes in multivariable analysis. CONCLUSIONS: Older community-dwelling people, prescribed ≥2 STOPP PIP are more likely to report ADEs, poorer health related quality of life and attend the accident & emergency department over 2-year follow-up.

External validation of the Probability of repeated admission (Pra) risk prediction tool in older community-dwelling people attending general practice: a prospective cohort study.

OBJECTIVES: Emergency admission is associated with the potential for adverse events in older people and risk prediction models are available to identify those at highest risk of admission. The aim of this study was to externally validate and compare the performance of the Probability of repeated admission (Pra) risk model and a modified version (incorporating a multimorbidity measure) in predicting emergency admission in older community-dwelling people. SETTING: 15 general practices (GPs) in the Republic of Ireland. PARTICIPANTS: n=862, ≥70 years, community-dwelling people prospectively followed up for 2 years (2010-2012). EXPOSURE: Pra risk model (original and modified) calculated for baseline year where ≥0.5 denoted high risk (patient questionnaire, GP medical record review) of future emergency admission. PRIMARY OUTCOME: Emergency admission over 1 year (GP medical record review). STATISTICAL ANALYSIS: descriptive statistics, model discrimination (c-statistic) and calibration (Hosmer-Lemeshow statistic). RESULTS: Of 862 patients, a total of 154 (18%) had ≥1 emergency admission(s) in the follow-up year. 63 patients (7%) were classified as high risk by the original Pra and of these 26 (41%) were admitted. The modified Pra classified 391 (45%) patients as high risk and 103 (26%) were subsequently admitted. Both models demonstrated only poor discrimination (original Pra: c-statistic 0.65 (95% CI 0.61 to 0.70); modified Pra: c-statistic 0.67 (95% CI 0.62 to 0.72)). When categorised according to risk-category model, specificity was highest for the original Pra at cut-point of ≥0.5 denoting high risk (95%), and for the modified Pra at cut-point of ≥0.7 (95%). Both models overestimated the number of admissions across all risk strata. CONCLUSIONS: While the original Pra model demonstrated poor discrimination, model specificity was high and a small number of patients identified as high risk. Future validation studies should examine higher cut-points denoting high risk for the modified Pra, which has practical advantages in terms of application in GP. The original Pra tool may have a role in identifying higher-risk community-dwelling older people for inclusion in future trials aiming to reduce emergency admissions.

Comparison of count-based multimorbidity measures in predicting emergency admission and functional decline in older community-dwelling adults: a prospective cohort study.

OBJECTIVES: Multimorbidity, defined as the presence of 2 or more chronic medical conditions in an individual, is associated with poorer health outcomes. Several multimorbidity measures exist, and the challenge is to decide which to use preferentially in predicting health outcomes. The study objective was to compare the performance of 5 count-based multimorbidity measures in predicting emergency hospital admission and functional decline in older community-dwelling adults attending primary care. SETTING: 15 general practices (GPs) in Ireland. PARTICIPANTS: n=862, ≥70 years, community-dwellers followed-up for 2 years (2010-2012). Exposure at baseline: Five multimorbidity measures (disease counts, selected conditions counts, Charlson comorbidity index, RxRisk-V, medication counts) calculated using GP medical record and linked national pharmacy claims data. PRIMARY OUTCOMES: (1) Emergency admission and ambulatory care sensitive (ACS) admission (GP medical record) and (2) functional decline (postal questionnaire). STATISTICAL ANALYSIS: Descriptive statistics and measure discrimination (c-statistic, 95% CIs), adjusted for confounders. RESULTS: Median age was 77 years and 53% were women. Prevalent rates ranged from 37% to 91% depending on which measure was used to define multimorbidity. All measures demonstrated poor discrimination for the outcome of emergency admission (c-statistic range: 0.62, 0.65), ACS admission (c-statistic range: 0.63, 0.68) and functional decline (c-statistic range: 0.55, 0.61). Medication-based measures were equivalent to diagnosis-based measures. CONCLUSIONS: The choice of measure may have a significant impact on prevalent rates. Five multimorbidity measures demonstrated poor discrimination in predicting emergency admission and functional decline, with medication-based measures equivalent to diagnosis-based measures. Consideration of multimorbidity in isolation is insufficient for predicting these outcomes in community settings.