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.

Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Evaluating awareness, knowledge and practice of healthcare professionals following implementation of a revised pregnancy prevention programme for isotretinoin in Ireland: A multi-stakeholder cross-sectional study.

PURPOSE: In 2018, following an EU-wide safety review, a revised pregnancy prevention programme (PPP) was introduced for isotretinoin (Roaccutane®). This study aimed to examine awareness, knowledge, and experience implementing the revised isotretinoin PPP in clinical practice across three healthcare professional (HCP) groups in Ireland. METHODS: A cross-sectional study using anonymous online surveys among general practitioners (GPs), community pharmacists, and specialist consultants was undertaken. Descriptive analyses are presented. RESULTS: Across all HCP groups there was high (≥87%) awareness that oral isotretinoin is contraindicated in women of childbearing potential (WCBP) unless the conditions of the PPP are fulfilled, but varying awareness among GPs (54.9%) and community pharmacists (45.9%) that exposure during pregnancy can cause both severe fetal malformations and spontaneous abortions. Implementation of the PPP in clinical practice varied across HCP groups. When initiating isotretinoin in WCBP, 66.7% of specialists and 40.8% of GPs indicated they had considered alternative treatment options, and 71.4% of specialists and 31.6% of GPs reported they first requested a pregnancy test. There was limited provision of the patient reminder card to WCBP, where 26.1% of community pharmacists provide this at each dispensing, while 47.6% of specialists and 11.8% of GPs ensured WCBP had a copy of the card when initiating treatment. Across all HCP groups, there was high (≥81.6%) awareness of the need for urgent consultation and immediate cessation of isotretinoin in the event of an unplanned or suspected pregnancy. CONCLUSIONS: Reinforcement of the provision and utilisation of the isotretinoin patient reminder card may be required, and further targeted education on specific elements of the PPP should be considered for GPs and community pharmacists.

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.

Short-Term Air Pollution as a Risk for Stroke Admission: A Time-Series Analysis.

BACKGROUND: The harmful effects of outdoor air pollution on stroke incidence are becoming increasingly recognised. We examined the impact of different air pollutants (PM2.5, PM10, NO2, ozone, and SO2) on admission for all strokes in two Irish urban centres from 2013 to 2017. METHODS: Using an ecological time series design with Poisson regression models, we analysed daily hospitalisation for all strokes and is-chaemic stroke by residence in Dublin or Cork, with air pollution level monitoring data with a lag of 0-2 days from exposure. Splines of temperature, relative humidity, day of the week, and time were included as confounders. Analysis was also performed across all four seasons. Data are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range (IQR) increase in each pollutant. RESULTS: There was no significant association between all stroke admission and any individual air pollutant. On seasonal analysis, during winter in the larger urban centre (Dublin), we found an association between all stroke cases and an IQR increase in NO2 (RR 1.035, 95% CI: 1.003-1.069), PM10 (RR 1.032, 95% CI: 1.007-1.057), PM2.5 (RR 1.024, 95% CI: 1.011-1.039), and SO2 (RR 1.035, 95% CI: 1.001-1.071). There was no significant association found in the smaller urban area of Cork. On meta-analysis, there remained a significant association between NO2 (RR 1.013, 95% CI: 1.001-1.024) and PM2.5 (1.009, 95% CI 1.004-1.014) per IQR increase in each. DISCUSSION: Short-term air pollution in winter was found to be associated with hospitalisation for all strokes in a large urban centre in Ireland. As Ireland has relatively low air pollution internationally, this highlights the need to introduce policy changes to reduce air pollution in all countries.

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.

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.

Poststroke Cognitive Impairment in Model-Based Economic Evaluation: A Systematic Review.

INTRODUCTION: Cognitive impairment (CI) is a frequent consequence of stroke and is associated with increased costs and reduced quality of life. However, its inclusion in model-based economic evaluation for stroke is limited. OBJECTIVE: To identify, review, and critically appraise current models of stroke for use in economic evaluation, and to identify applicability to modeling poststroke CI. METHODS: PubMed, EMBASE, and the NHS Economic Evaluations Database (NHS EED) were systematically searched for papers published from January 2008 to August 2018. Studies that described the development or design of a model of stroke progression intended for use in economic evaluation were included. Abstracts were screened, followed by full text review of potentially relevant articles. Models that included CI were retained for data extraction, and among the remainder, models that included both stroke recurrence and disability were also retained. Relevance and potential for adaptation for modeling CI were assessed using a standard questionnaire. RESULTS: Forty modeling studies were identified and categorized into 4 groups: Markov disability/recurrence (k = 29); CI (k = 2); discrete event simulation (k = 4), and other (k = 5). Only 2 modeling studies included CI as an outcome, and both focused on narrow populations at risk of intracranial aneurysm. None of the models allowed for disease progression in the absence of a stroke recurrence. None of the included studies carried out any sensitivity analysis in relation to model design or structure. CONCLUSIONS: Current stroke models used in economic evaluation are not adequate to model poststroke CI or dementia, and will require adaptation to be used for this purpose.

Explaining income-related inequalities in cardiovascular risk factors in Tunisian adults during the last decade: comparison of sensitivity analysis of logistic regression and Wagstaff decomposition analysis.

BACKGROUND: It is important to quantify inequality, explain the contribution of underlying social determinants and to provide evidence to guide health policy. The aim of the study is to explain the income-related inequalities in cardiovascular risk factors in the last decade among Tunisian adults aged between 35 and 70 years old. METHODS: We performed the analysis by applying two approaches and compared the results provided by the two methods. The methods were global sensitivity analysis (GSA) using logistic regression models and the Wagstaff decomposition analysis. RESULTS: Results provided by the two methods found a higher risk of cardiovascular diseases and diabetes in those with high socio-economic status in 2005. Similar results were observed in 2016. In 2016, the GSA showed that education level occupied the first place on the explanatory list of factors explaining 36.1% of the adult social inequality in high cardiovascular risk, followed by the area of residence (26.2%) and income (15.1%). Based on the Wagstaff decomposition analysis, the area of residence occupied the first place and explained 40.3% followed by income and education level explaining 19.2 and 14.0% respectively. Thus, both methods found similar factors explaining inequalities (income, educational level and regional conditions) but with different rankings of importance. CONCLUSIONS: The present study showed substantial income-related inequalities in cardiovascular risk factors and diabetes in Tunisia and provided explanations for this. Results based on two different methods similarly showed that structural disparities on income, educational level and regional conditions should be addressed in order to reduce inequalities.

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.

Drug-Drug Interactions and Their Association with Adverse Health Outcomes in the Older Community-Dwelling Population: A Prospective Cohort Study.

BACKGROUND: Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited. OBJECTIVE: We estimate potentially clinically important DDI prevalence and examine the association between DDIs and (1) adverse drug events (ADEs), (2) emergency hospital attendance and (3) health-related quality of life (HRQoL) in an older community-dwelling population in Ireland. METHODS: This is a prospective cohort study of community-dwelling older adults (N = 904) aged ≥ 70 years from 15 general practices in Ireland recruited in 2010 (wave-1) and followed-up over 2 years (wave-2; 2012-2013), with linked national pharmacy claims data. Individuals dispensed two or more drugs (wave-1: N = 842; wave-2: N = 763) were included. DDI prevalence at baseline, follow-up and 6 months prior to each health outcome was estimated. Multi-level regression was used to model the association between DDI-exposure and health outcomes at follow-up. DDI prevalence, adjusted incidence-rate ratios (aIRR), adjusted odds ratios (aOR), ß coefficients and robust standard error (RSE) from multi-level regression analyses, and 95% confidence intervals (CIs) are reported. RESULTS: At wave-1, n = 196 (23.3% [95% CI 20.5-26.3]), individuals were potentially exposed to ≥ 1 DDI, increasing to n = 345 (45.2% [41.7-48.9]) at wave-2. At 2-year follow-up, the median number of ADEs was 3 (interquartile range [IQR 2-5]); 229 (30.1%) had ≥ 1 emergency hospital attendance, and the mean EQ-5D was 0.74 (± 0.23). Evidence for the association between DDI-exposure and emergency hospital attendance at follow-up was lacking (aOR = 1.38 [0.42-4.53]). DDI-exposure was associated with an increasing number of ADEs (aIRR = 1.26 [1.03-1.55]), and decreasing EQ-5D utility (ß = - 0.07, [-0.11 to -0.04], RSE = 0.02). Aspirin-warfarin, clarithromycin-prednisolone, amiodarone-furosemide, clarithromycin-salbutamol, rosuvastatin-warfarin, amiodarone-bisoprolol, and aspirin-nicorandil were common DDIs 6 months preceding these health outcomes. CONCLUSIONS: We found a two-fold increase in DDI prevalence between wave 1 and 2. DDI exposure was associated with increasing ADEs and declining HRQoL at 2-year follow-up. Common DDIs involved anticoagulants, cardiovascular and antimicrobial drugs, which should be targeted for medicine optimisation.

Trends in polysubstance use among patients in methadone maintenance treatment in Ireland: Evidence from urine drug testing 2010-2020.

INTRODUCTION: The benefits of methadone maintenance treatment (MMT) may be compromised by the continued use of other substances during treatment. Polysubstance use has been identified as a major contributing factor to treatment discontinuation, a known risk factor for drug overdose. We examined trends in immunoassay drug positivity rates for amphetamines, benzodiazepines, cannabis, cocaine and opioids, and (2) trends in polysubstance positivity rates for drug combinations associated with increased risk of drug overdose among patients attending the national drug treatment centre in Ireland for MMT between 2010 and 2020. METHODS: Repeated cross-sectional study of patients attending the national drug treatment centre (NDTC) for MMT (total N = 1942) between 2010 and 2020, focused on urine drug samples provided for testing to the NDTC clinical testing laboratory (n = 221,564). Samples were analysed using immunoassay during the study period. Mixed-effects logistic regression models evaluate time trends in drug positivity. A random intercept accounts for repeat testing of individual patients. The study reports Adjusted Odds Ratios (AOR) for time (per year) with 95 % Confidence Intervals (95 % CI). RESULTS: Drug positivity rates increased over time for benzodiazepines (AOR 1.02, 95 % CI 1.01-1.03, p < .0001), cannabis (AOR 1.06, 95 % CI 1.05-1.08, p < .0001) and cocaine (AOR 1.28, 95 % CI 1.27-1.29, p < .0001), with decreasing trends for opioids (AOR 0.91, 95 % CI 0.91-0.92, p < .0001). Methadone and benzodiazepines were co-detected in over two-thirds of all samples during the study period. Co-detection of methadone and benzodiazepines with cocaine was also found to be increasing (AOR 1.24, 95 % CI 1.23-1.25, p < .0001), with weighted polysubstance positivity rates reaching 29.2 % in 2020. The co-detection of methadone and benzodiazepines with opioids decreased over the study period (AOR 0.92, 95 % CI 0.91-0.92, p < .0001), ranging from 36.7 % in 2010 to 26.9 % in 2020. CONCLUSION: Interventions are needed to target the persistently high use of benzodiazepines among patients in receipt of methadone due to their synergistic effects with opioids on respiratory depression, enhancing the risk of overdose. The growing use of cocaine among people in MMT also needs to be addressed.

Optimizing Patient Selection for Physiological Pacing in Bradyarrhythmia: Factors Associated With High Ventricular Pacing Burden.

Background: Right ventricular (RV) pacing is established as the most common ventricular pacing (VP) strategy for patients with symptomatic bradyarrhythmia. Some patients with high VP burden suffer deterioration of left ventricular (LV) function, termed pacing-induced cardiomyopathy (PICM). Patients who pace > 20% of the time from the RV apex are at increased risk of PICM, but independent predictors of increased RV pacing burden have not been elucidated in those who have a permanent pacemaker (PPM) inserted for bradyarrhythmia. Methods: We aimed to identify factors that are associated with increased VP burden > 20%, hence determining those at risk for resultant PICM. In this retrospective cohort study, we identified the most recent 300 consecutive cardiac implantable electronic device (CIED) implants in our center and collected past medical history, electrocardiogram (ECG), echo, medication and pacemaker check data. Results: A total of 236 individuals met inclusion criteria. Of the patients, 35% had RV pacing burden < 20%, while 65% had VP burden ≥ 20%; 96.2% of patients with complete heart block (CHB) paced > 20% (P = 0.002). Utilization of DDD or VVI (75.2% and 89.2% of patients, respectively) without mode switch algorithms was associated with VP > 20% (P < 0.001). Male or previous coronary artery bypass grafting (CABG) patients also statistically paced > 20%. Other factors trending towards significance included prolonged PR interval, atrial fibrillation or more advanced age. Conclusion: High-grade atrioventricular (AV) block was associated with an RV pacing burden > 20% over 3 years but this was not consistent in patients with only transient episodes of high-grade AV block. We found a significant association between high VP% and male sex, previous CABG and the absence of mode switching algorithms.

Examining the impact of COVID-19 disruptions on population-based breast cancer screening in Ireland.

OBJECTIVE: Many population-based breast screening programmes temporarily suspended routine screening following the COVID-19 pandemic onset. This study aimed to describe screening mammography utilisation and the pattern of screen-detected breast cancer diagnoses following COVID-19-related screening disruptions in Ireland. METHODS: Using anonymous aggregate data from women invited for routine screening, three time periods were examined: (1) January-December 2019, (2) January-December 2020, and (3) January-December 2021. Descriptive statistics were conducted and comparisons between groups were performed using chi-square tests. RESULTS: In 2020, screening mammography capacity fell by 67.1% compared to 2019; recovering to 75% of mammograms performed in 2019, during 2021. Compared to 2019, for screen-detected invasive breast cancers, a reduction in Grade 1 (14.2% vs. 17.2%) and Grade 2 tumours (53.4% vs. 58.0%) and an increase in Grade 3 tumours (32.4% vs. 24.8%) was observed in 2020 (p = 0.03); whereas an increase in Grade 2 tumours (63.3% vs. 58.0%) and a reduction in Grade 3 tumours (19.6% vs. 24.8%) was found in 2021 (p = 0.02). No changes in oestrogen receptor-positive or nodal-positive diagnoses were observed; however the proportion of oestrogen/progesterone receptor-positive breast cancers significantly increased in 2020 (76.2%; p < 0.01) and 2021 (78.7%; p < 0.001) compared to 2019 (67.8%). CONCLUSION: These findings demonstrate signs of a grade change for screen-detected invasive breast cancers early in the pandemic, with recovery evident in 2021, and without an increase in nodal positivity. Future studies are needed to determine the COVID-19 impact on long-term breast cancer outcomes including mortality.

Prevalence of Drug-Drug Interactions in Older Community-Dwelling Individuals: A Systematic Review and Meta-analysis.

BACKGROUND: Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults. METHODS: PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥ 65 years. Nursing home and inpatient hospital studies were excluded. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analysis was performed using a random-effects model with logit transformation. Heterogeneity was evaluated using Cochran's Q and I2. DDI prevalence and 95% confidence intervals (CIs) are presented. All analyses were performed in R (version 4.1.2). RESULTS: There were 5144 unique articles identified. Thirty-three studies involving 17,011,291 community-dwelling individuals aged ≥ 65 years met inclusion criteria. Thirty-one studies reported DDI prevalence at the study-participant level, estimates ranged from 0.8% to 90.6%. The pooled DDI prevalence was 28.8% (95% CI 19.3-40.7), with significant heterogeneity (p < 0.10; I2 = 100%; tau2 = 2.13) largely explained by the different DDI identification methods. Therefore, 26 studies were qualitatively synthesised and seven studies were eligible for separate meta-analyses. In a meta-analysis of three studies (N = 1122) using Micromedex®, pooled DDI prevalence was 57.8% (95% CI 52.2-63.2; I2 = 69.6%, p < 0.01). In a meta-analysis of two studies (N = 809,113) using Lexi-Interact®, pooled DDI prevalence was 30.3% (95% CI 30.2-30.4; I2 = 6.8%). In a meta-analysis of two studies (N = 947) using the 2015 American Geriatrics Society Beers criteria®, pooled DDI prevalence was 16.6% (95% CI 5.6-40.2; I2 = 97.5%, p < 0.01). Common DDIs frequently involved cardiovascular drugs, including ACE inhibitor-potassium-sparing diuretic; amiodarone-digoxin; and amiodarone-warfarin. CONCLUSIONS: DDIs are prevalent among older community-dwelling individuals; however, the methodology used to estimate these events varies considerably. A standardised methodology is needed to allow meaningful measurement and comparison of DDI prevalence.

Testing the effectiveness of a Fatigue and Activity Management Education for Work (FAME-W) intervention for individuals with inflammatory arthritis: Study protocol for a randomized control trial.

BACKGROUND: A work-focused fatigue management intervention, Fatigue and Activity Management Education for Work (FAME-W) programme was developed for individuals with inflammatory arthritis (IA) to manage fatigue in order to maintain demands of their work activities and tasks. This paper presents the protocol for a randomized control trial that will test the effectiveness and acceptability of FAME-W in improving work performance. METHODS: This protocol presents a multisite randomized control trial and mixed methods process evaluation. Eligible participants will be aged 18-65 years with a diagnosis of inflammatory arthritis and will be in paid employment. The primary outcome of the study will be Work Role Functioning (WRF) questionnaire, and the secondary outcomes will be fatigue, mood, health-related quality of life (HRQOL) and pain. Data will be collected immediately pre- and post-intervention and at 3 months of follow-up. The process evaluation will consist of focus groups and individual interviews to explore participants' experiences of FAME-W. Occupational therapists delivering the programme will complete a facilitator log to assess the fidelity and quality of intervention implementations. Facilitators will participate in individual interviews to explore intervention delivery and acceptability. RESULTS: Results will be expected to show that FAME-W will improve work performance by helping participants gain self-management strategies around managing fatigue and other symptoms related to fatigue. CONCLUSION: It is hoped that FAME-W will be an effective and acceptable intervention for individuals with IA in improving work performance by helping them manage their symptoms. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05138445, Registered on 30 November 2021.

Feasibility Randomised Control Trial of OptiMal: A Self-Management Intervention for Cancer Survivors.

PURPOSE: Cancer survivors can experience symptoms such as fatigue, pain and distress that persist for many months following treatment. These enduring symptoms often impact on participation in self-care activities, returning to school and/or work, and leisure and social activities. Self-management support is increasingly recognised as a core aspect of cancer survivorship care to reduce the impact of persistent symptoms. The purpose of this study was to examine the feasibility and potential effectiveness of a group-based self-management intervention, OptiMal, to improve the physical and psychological health of cancer survivors. OptiMal is a six-week intervention comprising weekly sessions on fatigue, stress and physical activity, diet and effective communication strategies. METHODS: A feasibility randomised control trial was undertaken. Individuals up to two years after cancer treatment were randomised to OptiMal or usual care. Feasibility was examined through recruitment and retention metrics. Potential effectiveness was tested through patient-reported outcomes collected at baseline and three months post-intervention. Descriptive and inferential statistics were used to analyse study data. RESULTS: Recruitment for this study was 32.5% (80/246 eligible individuals) with 77.5% retention at three-month follow-up (82.5% for intervention group and 72.5% for control group). Of those who attended the intervention, 19 (73%) attended all OptiMal sessions, indicating high adherence to the intervention. The majority of participants had breast cancer and were between 12 and 24 months post-treatment. The intervention group (n = 29) had statistically significant greater improvements in anxiety (p = 0.04) and health-related quality of life (health index score: p = 0.023, visual analogue score: p = 0.035) at three months post-intervention than the control group. CONCLUSIONS: Recruitment and retention in this study was similar to other cancer trials and the high adherence rate indicates that OptiMal is an acceptable self-management intervention for cancer survivors and warrants further investigation. OptiMal is intended to address symptoms reported across different cancer types. However, a limitation of this study was that the majority of participants had breast cancer, and therefore, generalisability of findings cannot be assumed for other cancer types. Future studies of OptiMal therefore need to use different strategies to recruit survivors of other cancer types.

Prescription drugs with potential for misuse: protocol for a multi-indicator analysis of supply, detection and the associated health burden in Ireland between 2010 and 2020.

INTRODUCTION: There is an increasing concern about the misuse of prescription drugs. Misuse refers to the intentional repurposing of prescribed drugs and/or the use of illicitly sourced prescription drugs, which may be counterfeit or contaminated. Drugs with the greatest potential for misuse are prescription opioids, gabapentinoids, benzodiazepines, Z-drugs and stimulants. OBJECTIVE: The aim of this study is to provide a comprehensive analysis of the supply, patterns of use and health burden associated with prescription drugs with potential for misuse (PDPM) in Ireland between 2010 and 2020. Three inter-related studies will be carried out. The first study will describe trends in supply of PDPM using law enforcement drug seizures data and national prescription records from national community and prison settings. The second study aims to estimate trends in the detection of PDPM across multiple early warning systems using national forensic toxicology data. The third study aims to quantify the health burden associated with PDPM nationally, using epidemiological indicators of drug-poisoning deaths, non-fatal intentional drug overdose presentations to hospitals and drug treatment demand. METHODS AND ANALYSIS: A retrospective observational study design, with repeated cross-sectional analyses, using negative binomial regression models or, where appropriate, joinpoint regression. ETHICS AND DISSEMINATION: The study has received approval from the RCSI Ethics Committee (REC202202020). Results will be disseminated in peer-reviewed journals, scientific and drug policy meetings and with key stakeholders via research briefs.

Global Incidence and Risk Factors Associated With Postoperative Urinary Retention Following Elective Inguinal Hernia Repair: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) Study.

Importance: Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors. Objective: To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR. Design, Setting, and Participants: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR. Exposure: Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia. Main Outcomes and Measures: The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients. Results: In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72). Conclusions: The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies.

Comparing characteristics of suicide to non-suicide drug poisoning deaths, by sex, in Ireland.

BACKGROUND: Suicide by drug poisoning is potentially preventable; however, evidence on associated risk factors by sex is limited. AIM: To assist in understanding how individual and social contextual factors, and specific drugs, influence risk of suicide compared to non-suicide drug poisoning deaths, and how this differs by sex. METHODS: Data were extracted from the National Drug-Related Deaths Index. Analysis included univariable and multivariable logistic regression to estimate unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for factors associated with suicide drug poisoning deaths (SDPD) (primary outcome) compared with non-suicide drug poisoning deaths (NSDPD) and stratified by sex. RESULTS: SDPD accounted for 240 (22%) of 1114 poisoning deaths, the majority among men (n = 147, 61%). Increasing age, mental ill health (AOR 7.85, 95% CI: 5.46-11.28), chronic pain (AOR 5.57, 95% CI: 3.28-9.46), and history of previous overdose (AOR 5.06, 95% CI: 3.39-7.56) were associated with increased odds of SDPD, with similar results for both sexes. The main drugs associated with SDPD were non-opioid analgesics (OR 4.06 [95% CI 2.66-6.18]), antipsychotics (OR 2.42 [95% CI 1.63-3.60]) and antidepressants (OR 2.18 [95% CI 1.59-2.97]). Pregabalin was associated with SDPD among women only. LIMITATIONS: Secondary analysis of coronial data on drug poisoning deaths therefore findings may not be relevant to suicide deaths in general. CONCLUSIONS: Ongoing monitoring for signs of suicidal intent in individuals with mental illness, chronic pain, overdose, and/or prescribed mental health medications may identify individuals in need of additional intervention.