Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

INTRODUCTION: Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC.  We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. METHODS: We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. RESULTS: A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P  = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. CONCLUSIONS: There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.

Drug-drug interactions and the risk of adverse drug reaction-related hospital admissions in the older population.

AIMS: The aims of this study were to estimate potentially clinically important drug-drug interaction (DDI) prevalence, and the average causal effect of DDI exposure on adverse drug reaction (ADR)-related hospital admission, and to examine differences in health-related quality of life (HRQoL) and length of stay (LOS) per DDI exposure in an older (≥65 years) population acutely hospitalized. METHODS: This was a cross-sectional study conducted among 798 older individuals acutely admitted to hospital in Ireland between 2016 and 2017. Medication (current/recently discontinued/over-the-counter) and clinical data (e.g., creatinine clearance) were available. DDIs were identified using the British National Formulary (BNF) and Stockley's Drug Interactions. Causal inference models for DDI exposure on ADR-related hospital admission were developed using directed acyclic graphs. Multivariable logistic regression was used to estimate the average causal effect. Differences in HRQoL (EQ-5D) and LOS per DDI exposure were examined non-parametrically. DDI prevalence, adjusted odds ratios (aOR), and 95% confidence intervals (CIs) are reported. RESULTS: A total of 782 (98.0%) individuals using two or more drugs were included. Mean age was 80.9 (SD ± 7.5) years (range: 66-105); 52.2% were female; and 45.1% (n = 353) had an ADR-related admission. At admission, 316 (40.4% [95% CI: 37.0-43.9]) patients had at least one DDI. The average causal effect of DDI exposure on ADR-related hospital admission was aOR = 1.21 [95% CI: 0.89-1.64]. This was significantly increased by exposure to: DDIs which increase bleeding risk (aOR = 2.00 [1.26-3.12]); aspirin-warfarin (aOR = 2.78 [1.37-5.65]); and esomeprazole-escitalopram (aOR = 3.22 [1.13-10.25]. DDI-exposed patients had lower HRQoL (mean EQ-5D = 0.49 [±0.39]) compared those non-DDI-exposed (mean EQ-5D = 0.57 [±0.41]), (P = .03); and greater median LOS in hospital (8 [IQR5-16]days) compared those non-DDI-exposed (7 [IQR 4-14] days),(P = .04). CONCLUSIONS: Potentially clinically important DDIs carry an increased average causal effect on ADR-related admission, significantly (two-fold) by exposure to DDIs that increase bleeding risk, which should be targeted for medicine optimization.

Lessons learned from COVID-19: improving breast cancer care post-pandemic from the patient perspective.

BACKGROUND: Since the onset of the pandemic, breast cancer (BC) services have been disrupted in most countries. The purpose of this qualitative study is to explore the unmet needs, patient-priorities, and recommendations for improving BC healthcare post-pandemic for women with BC and to understand how they may vary based on social determinants of health (SDH), in particular socio-economic status (SES). METHODS: Thirty-seven women, who were purposively sampled based on SDH and previously interviewed about the impact of COVID-19 on BC, were invited to take part in follow-up semi-structured qualitative interviews in early 2023. The interviews explored their perspectives of BC care since the easing of COVID-19 government restrictions, including unmet needs, patient-priorities, and recommendations specific to BC care. Thematic analysis was conducted to synthesize each topic narratively with corresponding sub-themes. Additionally, variation by SDH was analyzed within each sub-theme. RESULTS: Twenty-eight women (mean age = 61.7 years, standard deviation (SD) = 12.3) participated in interviews (response rate = 76%). Thirty-nine percent (n = 11) of women were categorized as high-SES, while 61% (n = 17) of women were categorized as low-SES. Women expressed unmet needs in their BC care including routine care and mental and physical well-being care, as well as a lack of financial support to access BC care. Patient priorities included the following: developing cohesion between different aspects of BC care; communication with and between healthcare professionals; and patient empowerment within BC care. Recommendations moving forward post-pandemic included improving the transition from active to post-treatment, enhancing support resources, and implementing telemedicine where appropriate. Overall, women of low-SES experienced more severe unmet needs, which in turn resulted in varied patient priorities and recommendations. CONCLUSION: As health systems are recovering from the COVID-19 pandemic, the emphasis should be on restoring access to BC care and improving the quality of BC care, with a particular consideration given to those women from low-SES, to reduce health inequalities post-pandemic.

Electrocardiographic predictors of response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan (SV) is currently recommended as a first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. AIMS: To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. METHODS: A retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association class II-III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-maximal-dose therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. Backward stepwise regression was employed to develop a parsimonious model. RESULTS: P-wave duration (PWD) 100-120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45-122.90), 5.00 (1.47-20.42), and 3.10 (1.18-9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). CONCLUSIONS: Prolongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.

Impact of the COVID-19 pandemic on women living with and beyond breast cancer: a qualitative study of women's experiences and how they varied by social determinants of health.

BACKGROUND: The aim of this study is to explore the general impact of COVID-19 on the access and use of BC services and support and overall well-being in women living with a diagnosis of breast cancer (BC) and to investigate how these experiences varied by the social determinants of health (SDH). METHODS: Semi-structured qualitative interviews were conducted with women selected through stratified purposive sampling to ensure data were available on information-rich cases. Interviews were conducted in early 2021 during government restrictions due to COVID-19. Thematic analysis was conducted to obtain overall experience and variation of experience based on SDH. RESULTS: Thirty seven women participated in interviews. Three major themes, with additional subthemes, emerged from analysis: 1. breast cancer services (screening, active treatment, and routine care); 2. breast cancer support and communication (continuity of care, role of liaison, and support services); and 3. quality of life (QoL) and well-being (emotional well-being; social well-being; and functional well-being). Women's experiences within the themes varied by socio-economic status (SES) and region of residence (urban/rural) specifically for BC services and support. CONCLUSION: The pandemic impacted women living with and beyond BC, but the impact has not been the same for all women. This study highlights areas for improvement in the context of BC care in Ireland and the findings will inform further policy and practice, including standardized BC services, improved communication, and enhancement of cancer support services.

Costs associated with adverse drug reactions in an older population admitted to hospital: a prospective cohort study.

PURPOSE: This study examines healthcare costs associated with adverse drug reactions (ADR) in an older population admitted acutely to an Irish tertiary hospital. METHODS: Prospective cohort study involving older persons admitted to hospital with and without an ADR. Data was collected at baseline, during hospitalisation and post-discharge. Participants provided information on healthcare resource use three months before admission (baseline) and three months after discharge (follow-up). For each healthcare resource, unit costs were derived and applied. The average cost (standard deviation (SD)) associated with the hospital admission for the ADR and non-ADR are presented. In addition, baseline and follow-up care costs were compared using difference-in-difference analysis and presented with 95% confidence intervals (CI). Costs by preventability and severity of ADR are also presented. RESULTS: A total of n = 230 participants were included (n = 93 ADR and n = 137 without ADR). The average cost associated with hospital admission for an ADR was €9538 (SD €10442) and €9828 (SD €11770) for non-ADR. The additional follow-up costs (difference-in-difference) associated with the ADR was estimated at €2047 (95% CI: -€889 to €4983). The mean incremental follow-up cost of definite preventable ADRs was estimated at €1648 (95% CI: -€4310 to €7605), possible preventable ADRs €2259 (95 CI: -€1194 to €5712) and unavoidable ADRs €1757 (95% CI: -€3377 to €6890). The mean incremental follow-up cost associated with moderate severe ADRs was estimated at €1922 (95% CI: -€1088 to €4932) and €3580 (95% CI: -€4898 to €12,058) for severe ADRs.  CONCLUSION: ADRs leading to hospital admission are associated with modest incremental healthcare costs during and three months after admission. Severe and possibly preventable ADRs were associated with higher costs.

Informing interventions to improve uptake of adjuvant endocrine therapy in women with breast cancer: a theoretical-based examination of modifiable influences on non-adherence.

PURPOSE: To inform intervention development, we measured the modifiable determinants of endocrine therapy (ET) non-adherence in women with breast cancer, using the Theoretical Domains Framework (TDF) and examined inter-relationships between these determinants and non-adherence using the Perceptions and Practicalities Approach (PAPA). METHODS: Women with stages I-III breast cancer prescribed ET were identified from the National Cancer Registry Ireland (N = 2423) and invited to complete a questionnaire. A theoretically based model of non-adherence was developed using PAPA to examine inter-relationships between the 14 TDF domains of behaviour change and self-reported non-adherence. Structural equation modelling (SEM) was used to test the model. RESULTS: A total of 1606 women participated (response rate = 66%) of whom 395 (25%) were non-adherent. The final SEM with three mediating latent variables (LVs) (PAPA Perceptions: TDF domains, Beliefs about Capabilities, Beliefs about Consequences; PAPA Practicalities: TDF domain, Memory, Attention, Decision Processes and Environment) and four independent LVs (PAPA Perceptions: Illness intrusiveness; PAPA Practicalities: TDF domains, Knowledge, Behaviour Regulation; PAPA External Factors: TDF domain, Social Identity) explained 59% of the variance in non-adherence and had an acceptable fit (χ2(334) = 1002, p < 0.001; RMSEA = 0.03; CFI = 0.96 and SRMR = 0.07) Knowledge had a significant mediating effect on non-adherence through Beliefs about Consequences and Beliefs about Capabilities. Illness intrusiveness had a significant mediating effect on non-adherence through Beliefs about Consequences. Beliefs about Consequences had a significant mediating effect on non-adherence through Memory, Attention, Decision Processesg and Environment. CONCLUSIONS: By underpinning future interventions, this model has the potential to improve ET adherence and, hence, reduce recurrence and improve survival in breast cancer.

Breast cancer care amidst a pandemic: a scoping review to understand the impact of coronavirus disease 2019 on health services and health outcomes.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, health services for breast cancer (BC) have been disrupted. Our scoping review examines the impact of the COVID-19 pandemic on BC services, health outcomes, and well-being for women. Additionally, this review identifies social inequalities specific to BC during the pandemic. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines, the literature search was conducted using scientific databases starting from March 2020 through November 2021. Studies were identified and selected by two researchers based on inclusion criteria, and the relevant data were extracted and charted to summarize the findings. Ninety-three articles were included in this review. Main themes included are as follows: (i) the impact of COVID-19 on BC services; (ii) the impact of COVID-19 on health outcomes and well-being in women with BC; and (iii) any variation in the impact of COVID-19 on BC by social determinants of health. There were apparent disruptions to BC services across the cancer continuum, especially screening services. Clinical repercussions were a result of such disruptions, and women with BC experienced worsened quality of life and psychosocial well-being. Finally, there were social inequalities dependent on social determinants of health such as age, race, insurance status, and region. Due to the disruption of BC services during the COVID-19 pandemic, women were impacted on their health and overall well-being. The variation in impact demonstrates how health inequities have been exacerbated during the pandemic. This comprehensive review will inform timely health-care changes to minimize long-term impacts of the pandemic and improve evidence-based multidisciplinary needs.

Longitudinal Medication Adherence in Older Adults With Multimorbidity and Association With Health Care Utilization: Results From the Irish Longitudinal Study on Ageing.

BACKGROUND: The association between objectively measured nonadherence and health care utilization in multimorbid older people is unclear. OBJECTIVE: To measure medication adherence across multiple chronic conditions, identify adherence patterns, and estimate the association between adherence and self-reported health care utilization. METHODS: This is a retrospective cohort study of multimorbid participants aged ≥70 years in the Irish LongituDinal Study on Ageing (TILDA). Eligible participants had linked pharmacy claims data and completed TILDA wave 2 (2 years after wave 1). The RxRisk-V tool was used to identify multimorbidity. Average adherence (AA) across RxRisk-V conditions was estimated using the CMA7 function (AdhereR). Group-based trajectory models (GBTMs) identified adherence patterns in the 12 months following wave 1. Negative binomial regression was used to estimate the association between adherence and the rate of subsequent self-reported general practitioner [GP] visits, emergency department (ED) visits, outpatient visits, and hospitalizations in the 12 months following adherence measurement (reported at wave 2). Adjusted Incident Rate Ratios (aIRR) and 95% CIs are presented. RESULTS: Higher AA (CMA7) was associated with a small significant decrease in GP visit rate (aIRR = 0.70; CI = 0.53-0.94) and outpatient visit rate (aIRR = 0.44; CI = 0.23-0.81). GBTM identified 6 adherence groups (n = 1050). Compared with high adherers, group 1 (rapid decline, modest increase) membership (aIRR = 1.72; CI = 1.09-2.73) and group 4 (high adherence, delayed decline) membership (aIRR = 1.92; CI = 1.19-3.05) significantly increased ED visit rate. CONCLUSION AND RELEVANCE: Suboptimal medication adherence in multimorbid older adults is associated with increased health care utilization. Identification of suboptimal adherence groups for medication management interventions may help decrease the health system burden and health care costs.

The psychosocial determinants of quality of life in breast cancer survivors: a scoping review.

BACKGROUND: Breast cancer care today involves state-of-the-art biomedical treatment but can fail to address the broader psychosocial and quality-of-life (QoL) issues associated with the transition to breast cancer survivorship. This scoping review examines the evidence on the influence of psychosocial determinants on QoL in breast cancer survivors. METHODS: Scoping review methodology was used to: (1) identify the research question(s); (2) identify relevant studies; (3) undertake study selection; (4) extract data; (5) collate, summarise and report the results. RESULTS: A total of 33 studies met the inclusion criteria. The majority of studies were conducted in the US (n = 22, 67%) and were mainly cross-sectional (n = 26, 79%). Sixteen psychosocial determinants of QoL were identified. Social support (n = 14, 42%), depression (n = 7, 21%) and future appraisal and perspective (n = 7, 21%) were the most frequently investigated determinants. Twelve different QoL measures were used. A range of different measurement tools were also used per psychosocial determinant (weighted average = 6). The 14 studies that measured the influence of social support on QoL employed 10 different measures of social support and 7 different measures of QoL. In general, across all 33 studies, a higher level of a positive influence and a lower level of a negative influence of a psychosocial determinant was associated with a better QoL e.g. higher social support and lower levels of depression were associated with a higher/better QoL. For some determinants such as spirituality and coping skills the influence on QoL varied, but these determinants were less commonly investigated. CONCLUSION: Consensus around measures of QoL and psychological determinants would be valuable and would enable research to determine the influence of psychosocial determinants on QoL adequately. Research in other healthcare settings beyond the US is required, in order to understand the influence of organisation and follow-up clinical and supportive care on psychosocial determinants and QoL and to improve the quality of care in breast cancer survivors.

Identifying Adherence Patterns Across Multiple Medications and Their Association With Health Outcomes in Older Community-Dwelling Adults With Multimorbidity.

OBJECTIVES: To classify older people with multimorbidity according to their adherence patterns and to examine the association between medication adherence and health outcomes. METHODS: This is a secondary analysis of a cohort study. Community-dwelling adults aged ≥70 years were recruited from 15 general practices in Ireland in 2010 (wave 1) and followed up 2 years later (wave 2). Participants had ≥2 RxRisk-V multimorbidity conditions at wave 1 and had ≥2 dispensations of RxRisk-V medications (wave 1-wave 2). Average adherence across RxRisk-V conditions was estimated based on continuous multiple-interval measure of medication availability (CMA7 function in AdhereR). Group-based trajectory models were used to group participants' adherence patterns for RxRisk-V medications. Multilevel regression was used to examine the association between adherence and (1) EuroQol 5-dimension (EQ-5D) utility (linear) and (2) vulnerability, using the Vulnerable Elders Survey (≥3 defined as vulnerable; logistic) at wave 2, controlling for potential confounders. RESULTS: Average adherence (CMA7) was 77% across 501 participants. Group-based trajectory models identified 5 adherence groups: (1) initial low adherers, gradual increase; (2) high adherers, sharp decline; (3) steady adherers, gradual decline; (4) consistent high adherers; and (5) consistent nonadherers. Higher average adherence was associated with a significant increase in EQ-5D utility (adjusted ß = 0.11, robust standard error 0.04). Group 5 was associated with significantly increased vulnerability compared to group 4 (adjusted odds ratio = 1.88; 95% confidence interval 1.01-3.50). CONCLUSION: Increased average adherence was associated with higher EQ-5D utility. Adherence grouping did not significantly impact utility. Suboptimal adherence to multiple medications in older adults with multimorbidity was associated with vulnerability.

Agreement between self-reported morbidity and pharmacy claims data for prescribed medications in an older community based population.

BACKGROUND: Studies have indicated variability around prevalence estimates of multimorbidity due to poor consensus regarding its definition and measurement. Medication-based measures of morbidity may be valuable resources in the primary-care setting where access to medical data can be limited. We compare the agreement between patient self-reported and medication-based morbidity; and examine potential patient-level predictors of discordance between these two measures of morbidity in an older (≥ 50 years) community-based population. METHODS: A retrospective cohort study was performed using national pharmacy claims data linked to The Irish LongituDinal study on Ageing (TILDA). Morbidity was measured by patient self-report (TILDA) and two medication-based measures, the Rx-Risk (< 65 years) and Rx-Risk-V (≥65 years), which classify drug claims into chronic disease classes. The kappa statistic measured agreement between self-reported and medication-based morbidity at the individual patient-level. Multivariate logistic regression was used to examine patient-level characteristics associated with discordance between measures of morbidity. RESULTS: Two thousand nine hundred twenty-five patients were included (< 65 years: N = 1095, 37.44%; and ≥ 65 years: N = 1830 62.56%). Hypertension and high cholesterol were the most prevalent self-reported morbidities in both age cohorts. Agreement was good or very good (κ = 0.61-0.81) for diabetes, osteoporosis and glaucoma; and moderate for high cholesterol, asthma, Parkinson's and angina (κ = 0.44-0.56). All other conditions had fair or poor agreement. Age, gender, marital status, education, poor-delayed recall, depression and polypharmacy were significantly associated with discordance between morbidity measures. CONCLUSIONS: Most conditions achieved only moderate or fair agreement between self-reported and medication-based morbidity. In order to improve the accuracy in prevalence estimates of multimorbidity, multiple measures of multimorbidity may be necessary. Future research should update the current Rx-Risk algorithms in-line with current treatment guidelines, and re-assess the feasibility of using these indices alone, or in combination with other methods, to yield more accurate estimates of multimorbidity.

The Need to Develop Standard Measures of Patient Adherence for Big Data: Viewpoint.

Despite half a century of dedicated studies, medication adherence remains far from perfect, with many patients not taking their medications as prescribed. The magnitude of this problem is rising, jeopardizing the effectiveness of evidence-based therapies. An important reason for this is the unprecedented demographic change at the beginning of the 21st century. Aging leads to multimorbidity and complex therapeutic regimens that create a fertile ground for nonadherence. As this scenario is a global problem, it needs a worldwide answer. Could this answer be provided, given the new opportunities created by the digitization of health care? Daily, health-related information is being collected in electronic health records, pharmacy dispensing databases, health insurance systems, and national health system records. These big data repositories offer a unique chance to study adherence both retrospectively and prospectively at the population level, as well as its related factors. In order to make full use of this opportunity, there is a need to develop standardized measures of adherence, which can be applied globally to big data and will inform scientific research, clinical practice, and public health. These standardized measures may also enable a better understanding of the relationship between adherence and clinical outcomes, and allow for fair benchmarking of the effectiveness and cost-effectiveness of adherence-targeting interventions. Unfortunately, despite this obvious need, such standards are still lacking. Therefore, the aim of this paper is to call for a consensus on global standards for measuring adherence with big data. More specifically, sound standards of formatting and analyzing big data are needed in order to assess, uniformly present, and compare patterns of medication adherence across studies. Wide use of these standards may improve adherence and make health care systems more effective and sustainable.

Developing a model of the determinants of medication nonadherence in older community-dwelling patients.

Medication nonadherence is associated with adverse health outcomes in older populations. The aim of this study was to develop a model that describes the relationship between the determinants of nonadherence, per the World Health Organization (WHO) model of nonadherence and the necessity-concerns framework (NCF) and nonadherence in a cohort of older community-dwelling patients. A retrospective cohort study of 855 community-dwelling patients aged ≥70 years from 15 practices. Medication nonadherence was assessed by (i) medication possession ratio (MPR < 80%) and (ii) the median MPR across all drugs dispensed. Patient questionnaires, interviews, and medical records measured the determinants of nonadherence per the WHO and NCF frameworks. Confirmatory factor analysis (CFA) was undertaken to generate the model of best fit. Two structural equation models (SEM) were developed to evaluate the relationship between the WHO factors, the NCF, and nonadherence (Model 1: MPR < 80%, Model 2: median MPR). The CFA produced a reasonable fit (χ2(113) = 203, p < .001; root mean square error of approximation = 0.03; comparative fit index = 0.98, and weighted root mean square residual = 0.97) and adequate internal consistency (r = .26-.40). SEM analysis (Model 1) showed a significant direct relationship between patient-related (ß = 0.45, p < .01), socioeconomic (ß = 0.20, p < .01), and therapy-related factors (ß = -0.27, p < .01) and nonadherence (MPR < 80%). Similar results were found for Model 2 (median MPR). There was a significant direct relationship between medication concerns (ß = -0.13, p < .01) and nonadherence. Therapy-related (ß = -0.04, p < .05) and patient-related factors (ß = -0.06, p < .05) also had a significant mediating effect on nonadherence through medication concerns. Health care professionals need to address medication concerns and management of adverse effects in older populations to improve adherence and clinical outcomes.

The association between medication non-adherence and adverse health outcomes in ageing populations: A systematic review and meta-analysis.

AIMS: The aim of this systematic review and meta-analysis was to synthesise the evidence relating to medication non-adherence and its association with health outcomes in people aged ≥50 years. METHODS: Seven databases were searched up to February 2019 for observational studies that measured medication (non-)adherence as a predictor of the following health outcomes in adults aged ≥50 years: healthcare utilisation (hospitalisation, emergency department visits, outpatient visits and general practitioner visits), mortality, adverse clinical events and quality of life. Screening and quality assessment using validated criteria were completed by 2 reviewers independently. Random effects models were used to generate pooled estimates of association using adjusted study results. The full methodological approach was published on PROSPERO (ID: CRD42017077264). RESULTS: Sixty-six studies were identified for qualitative synthesis, with 11 of these studies eligible for meta-analyses. A meta-analysis including 3 studies measuring medication non-adherence in adults aged ≥55 years showed a significant association with all-cause hospitalisation (adjusted odds ratio 1.17, 95% confidence interval [CI] 1.12, 1.21). A meta-analysis including 2 studies showed that medication non-adherence was not significantly associated with an emergency department visit (adjusted odds ratio 1.05, 95% CI 0.90, 1.22). Good adherence was associated with a 21% reduction in long-term mortality risk in comparison to medication non-adherence (adjusted hazard ratio 0.79, 95% CI 0.63, 0.98). CONCLUSION: Medication non-adherence may be significantly associated with all-cause hospitalisation and mortality in older people. Medication adherence should be monitored and addressed in this cohort to minimise hospitalisation, improve clinical outcomes and reduce healthcare costs.

Identifying Adverse Drug Events in Older Community-Dwelling Patients.

PURPOSE: To evaluate a patient-report instrument for identifying adverse drug events (ADEs) in older populations with multimorbidity in the community setting. METHODS: This was a retrospective cohort study of 859 community-dwelling patients aged ≥70 years treated at 15 primary care practices. Patients were asked if they had experienced any of a list of 74 symptoms classified by physiologic system in the previous 6 months and if (1) they believed the symptom to be related to their medication, (2) the symptom had bothered them, (3) they had discussed it with their family physician, and (4) they required hospital care due to the symptom. Self-reported symptoms were independently reviewed by 2 clinicians who determined the likelihood that the symptom was an ADE. Family physician medical records were also reviewed for any report of an ADE. RESULTS: The ADE instrument had an accuracy of 75% (95% CI, 77%-79%), a sensitivity of 29% (95% CI, 27%-31%), and a specificity of 93% (95% CI, 92%-94%). Older people who reported a symptom had an increased likelihood of an ADE (positive likelihood ratio [LR+]: 4.22; 95% CI, 3.78-4.72). Antithrombotic agents were the drugs most commonly associated with ADEs. Patients were most bothered by muscle pain or weakness (75%), dizziness or lightheadedness (61%), cough (53%), and unsteadiness while standing (52%). On average, patients reported 39% of ADEs to their physician. Twenty-six (3%) patients attended a hospital outpatient clinic, and 32 (4%) attended an emergency department due to ADEs. CONCLUSION: Older community-dwelling patients were often not correct in recognizing ADEs. The ADE instrument demonstrated good predictive value and could be used to differentiate between symptoms of ADEs and chronic disease in the community setting.

Association between adherence to antihypertensive medications and health outcomes in middle and older aged community dwelling adults; results from the Irish longitudinal study on ageing.

PURPOSE: To examine the association between antihypertensive medication (AHTM) implementation adherence and healthcare utilisation in community-dwelling adults aged ≥ 50 years in Ireland. METHODS: This was a prospective cohort study. The Irish Longitudinal Study on Ageing (TILDA) was linked to pharmacy claims data for participants aged ≥ 50 years. Participants were included if they had ≥ 3 pharmacy claims for one or more AHTM (ATC codes 'C02', 'C03', 'C07', 'C08' or 'C09') within the year preceding the year of self-reported healthcare utilisation outcome occurrence. Outcomes included self-reported general practitioner (GP), emergency department (ED), outpatient department visits and hospital admissions. Implementation adherence was measured using proportion of days covered (PDC), with participants classified as adherent if the average PDC ≥ 0.8. Negative binomial models were used to analyse the association between AHTM adherence and number of GP, ED, outpatient visits and hospitalisations (adjusted IRR and 95% CI are presented). RESULTS: One thousand four hundred thirty-one participants were included. The majority of participants (72.6%) were considered adherent. Good implementation adherence to AHTM was associated with a significant decrease in self-reported GP visits (adjusted IRR 0.91, 95% CI 0.83-0.99). Adherence had no significant impact on the number of ED visits, outpatient visits or hospitalisations reported by TILDA participants. CONCLUSIONS: Good adherence to AHTM was associated with less self-reported GP visits in this population, suggesting improved overall health status. However, the impact of medication non-adherence on the other self-reported healthcare utilisation outcomes (ED, outpatient visits and hospitalisations) was not evident in this study.

Impact of drug burden index on adverse health outcomes in Irish community-dwelling older people: a cohort study.

BACKGROUND: The Drug Burden Index (DBI) quantifies exposure to medications with anticholinergic and/or sedative effects. A consensus list of DBI medications available in Ireland was recently developed for use as a DBI tool. The aim of this study was to validate this DBI tool by examining the association of DBI score with important health outcomes in Irish community-dwelling older people. METHODS: This was a cohort study using data from The Irish Longitudinal Study on Ageing (TILDA) with linked pharmacy claims data. Individuals aged ≥65 years participating in TILDA and enrolled in the General Medical Services scheme were eligible for inclusion. DBI score was determined by applying the DBI tool to participants' medication dispensing data in the year prior to outcome assessment. DBI score was recoded into a categorical variable [none (0), low (> 0 and < 1), and high (≥1)]. Outcome measures included any Activities of Daily Living (ADL) impairment, any Instrumental Activities of Daily Living (IADL) impairment, any self-reported fall in the previous 12 months, any frailty criterion met (Fried Phenotype measure), quality of life (QoL) score (CASP-19 [Control Autonomy Self-realisation Pleasure] measure), and healthcare utilisation (any hospital admission and any emergency department (ED) visit) in the previous 12 months. Statistical analyses included multivariate logistic and linear regression models controlling for potential confounders. RESULTS: 61.3% (n = 1946) of participants received at least one DBI prescription in the year before their outcome assessment. High DBI exposure (DBI score ≥ 1) vs none was significantly associated with impaired function (ADL impairment adjusted OR 1.89, 95% CI 1.25, 2.88; IADL impairment adjusted OR 2.97, 95% CI 1.91, 4.61), self-reported falls (adjusted OR 1.50, 95%CI 1.03, 2.18), frailty (adjusted OR 1.74, 95% CI 1.14, 2.67), and reduced QoL (ß = - 1.84, 95%CI -3.14, - 0.54). There was no significant association between DBI exposure and healthcare utilisation. CONCLUSIONS: The findings validate the use of the DBI tool for predicting risk of functional impairment, falls, frailty and reduced QoL in older people in Ireland, and may be extended to other European countries. Integration of this tool into routine practice may be an appropriate step forward to improve outcomes in older people.

Benzodiazepine and Z-drug prescribing in Ireland: analysis of national prescribing trends from 2005 to 2015.

AIMS: The aim of this study was to examine prescribing trends for benzodiazepines and Z-drugs to General Medical Services (GMS) patients in Ireland. METHODS: A repeated cross-sectional analysis of the national pharmacy claims database was conducted for GMS patients aged ≥16 years from 2005 to 2015. Prescribing rates per 1000 eligible GMS population were calculated with 95% confidence intervals (CIs). Negative binomial regression was used to determine longitudinal trends and compare prescribing rates across years, gender and age groups. Duration of supply and rates of concomitant benzodiazepine and Z-drug prescribing were determined. Age (16-44, 45-64, ≥65 years) and gender trends were investigated. RESULTS: Benzodiazepine prescribing rates decreased significantly from 225.92/1000 population (95% CI 224.94-226.89) in 2005 to 166.07/1000 population (95% CI 165.38-166.75) in 2015 (P < 0.0001). Z-drug prescribing rates increased significantly from 95.36/1000 population (95% CI 94.73-96.00) in 2005 to 109.11/1000 population (95% CI 108.56-109.67) in 2015 (P = 0.048). Approximately one-third of individuals dispensed either benzodiazepines or Z-drugs were receiving long-term prescriptions (>90 days). The proportion of those receiving >1 benzodiazepine and/or Z-drug concomitantly increased from 11.9% in 2005 to 15.3% in 2015. Benzodiazepine and Z-drug prescribing rates were highest for older women (≥65 years) throughout the study period. CONCLUSIONS: Benzodiazepine prescribing to the GMS population in Ireland decreased significantly from 2005 to 2015, and was coupled with significant increases in Z-drug prescribing. The study shows that benzodiazepine and Z-drug prescribing is common in this population, with high proportions of individuals receiving long-term prescriptions. Targeted interventions are needed to reduce potentially inappropriate long-term prescribing and use of these medications in Ireland.

Measuring medication adherence in older community-dwelling patients with multimorbidity.

PURPOSE: Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on adherence. METHODS: This is a retrospective cohort study of medication adherence in 855 community-dwelling patients aged ≥ 70 years from 15 practices in Ireland using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. Multimorbidity was measured using the RxRisk-V and by the number of different drug classes. The RxRisk-V algorithm classifies prescription drug fills into 45 chronic disease classes for older populations based on the WHO Anatomical Therapeutic Chemical classification system. Adherence to medications was assessed by: (i) calculating the average medication possession ratio (MPR) per patient and (ii) an MPR< 80%. RESULTS: The overall median MPR for the cohort was 0.83 (IQR 0.69, 0.91). The conditions with the highest MPRs were hypothyroidism (mean MPR = 0.88, SD = 0.20) and type 2 diabetes (mean MPR = 0.83, SD = 0.19), followed by heart disease. On average, 20-40% of patients were non-adherent (MPR < 80%) across all conditions. There was an inverted U-shaped relationship between the mean MPR and number of morbidities and drug classes. Adherence varied per patients' morbidity burden, with higher adherence for certain combinations of chronic conditions. CONCLUSION: In total, 31% of older patients with multimorbidity were non-adherent to their medication but adherence levels varied across treatment categories and chronic conditions.