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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), β 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 (β = − 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Older patients are at increased risk of drug-drug interactions (DDIs) due to polypharmacy. Cardiovascular and central nervous system (CNS) drugs are commonly implicated in serious DDIs. Objectives: This study aimed to determine the prevalence and factors associated with potential 'severe' cardiovascular and CNS DDIs among older (≥ 70 years) community-dwellers. Methods: This was a prospective cohort study using linked data from a national pharmacy claims database and waves 1 and 2 of The Irish LongituDinal study on Ageing (TILDA). 'Severe' cardiovascular and CNS DDIs were identified using the British National Formulary 77 and Stockley's Drug Interactions. The prevalence of 'severe' DDIs (any DDI vs. none) was calculated. Logistic regression was used to examine the association between sociodemographic, functional ability, and medication-related factors and the risk of DDI exposure between waves 1 and 2. Results: A total of 1466 patients were included [mean age (standard deviation) = 78 (5.5) years; female n = 795, 54.2%]. In total, 332 community-dwellers aged ≥ 70 years [22.65%, 95% confidence interval (CI) 20.58–24.86] were potentially exposed to at least one 'severe' cardiovascular or CNS DDI, with more than half (54.82%) of this cohort dispensed the same DDI for a prolonged time (≥ 3 consecutive claims). Aspirin-warfarin was the most frequently dispensed (co-prescribed) DDI (n = 34, 10.24%, 95% CI 7.39–14.00), followed by atorvastatin-clarithromycin (n = 19, 5.72%, 95% CI 3.64–8.81). Polypharmacy [≥ 10 vs. < 5 drugs, odds ratio (OR) 13.40, 95% CI 8.22–21.85] and depression (depressed vs. not, OR 2.12, 95% CI 1.34–3.34) were significantly associated with these DDIs, after multivariable adjustment. Conclusion: 'Severe' cardiovascular and CNS DDIs are prevalent in older community-dwellers in Ireland, and those with polypharmacy and depression are at a significantly increased risk. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to examine the prevalence of coronary heart disease (CHD)–related disability (hereafter also "disability") and the impact of CHD risk factors on disability in older adults in the Republic of Ireland (ROI) and Northern Ireland (NI). Method: Population attributable fractions were calculated using risk factor relative risks and disability prevalence derived from The Irish Longitudinal Study on Ageing and the Northern Ireland Health Survey. Results: Disability was significantly lower in ROI (4.1% vs. 8.8%). Smoking and diabetes prevalence rates, and the fraction of disability that could be attributed to smoking (ROI: 6.6%; NI: 6.1%), obesity (ROI: 13.8%; NI: 11.3%), and diabetes (ROI: 6.2%; NI: 7.2%), were comparable in both countries. Physical inactivity (31.3% vs. 54.8%) and depression (10.2% vs. 17.6%) were lower in ROI. Disability attributable to depression (ROI: 16.3%; NI: 25.2%) and physical inactivity (ROI: 27.5%; NI: 39.9%) was lower in ROI. Discussion: Country-specific similarities and differences in the prevalence of disability and associated risk factors will inform public health and social care policy in both countries. [ABSTRACT FROM AUTHOR]

Background Hypertension is a global public health challenge. National prevalence estimates can conceal important differences in prevalence in subnational areas. This paper aims to develop a consistent set of national and subnational estimates of the prevalence of hypertension in a country with limited data for subnational areas. Methods A nationally representative cross-sectional Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007 was used to identify risk factors and develop a national and a subnational model of the risk of self-reported, doctor-diagnosed hypertension among adults aged 18+ years in the Republic of Ireland. The subnational model's group-specific risk estimates were applied to group-specific population count estimates for subnational areas to estimate the number of adults with doctor-diagnosed hypertension in subnational areas in 2007. A subsample of older adults aged 45+ years who also had their blood pressure objectively measured using a sphygmomanometer was used to estimate the national prevalence of diagnosed and undiagnosed hypertension among adults aged 45+ years. Results The prevalence of self-reported, doctor-diagnosed hypertension among adults aged 18+ years was 12.6% (95% CI = 11.7% - 13.4%). After adjustment for other explanatory variables the risk of self-reported, doctor-diagnosed hypertension was significantly related to age (p < 0.001), body mass index (p < 0.001), smoking (p = 0.001) and fruit and vegetable consumption (p = 0.003). Among adults aged 45+ years the prevalence of undiagnosed hypertension (38.7% (95% CI 34.6% - 42.8%)) was higher than self-reported, doctordiagnosed hypertension (23.4% (95% CI = 22.0% - 24.7%)). Among adults aged 45+ years, the prevalence of undiagnosed hypertension was higher among men (46.8%, 95% CI 41.2% - 52.4%) than women (31.2%, 95% CI 25.7% - 36.6%). There was no significant variation in the prevalence of self-reported, doctor-diagnosed hypertension across subnational areas. Conclusions Services need to manage diagnosed hypertension cases and to detect and manage undiagnosed cases. Further population level improvements in lifestyle risk factors for hypertension are key in developing a more integrated approach to prevent cardiovascular disease. Better subnational data on hypertension outcomes and risk factors are needed to better describe the distribution of hypertension risk and hypertension prevalence in subnational areas. [ABSTRACT FROM AUTHOR]

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., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: This study aimed to examine trends in valproate use among women of childbearing potential (WCBP) aged 16-44 years in Ireland following two European-directed regulatory interventions in December 2014 and April 2018., Methods: This was a repeated cross-sectional study using monthly national pharmacy claims data, to examine trend changes in the prevalence of valproate use among WCBP pre and post two separate regulatory events in December 2014 and April 2018. Annual population estimates from the Central Statistics Office were used to calculate the prevalence rate per 1000 eligible women. Segmented regression analysis of interrupted time series with negative binomial regression was used to examine rates for WCBP aged 16-44 years, and by 10-year age groups. Prevalence ratios (PR) are presented with 95% confidence intervals (CIs)., Results: Among WCBP aged 16-44 years, there was no statistically significant change in the month-to-month prevalence ratio in the post- compared to pre-December 2014 intervention period. A significant decline was, however, observed in the post-, compared to pre-April 2018 intervention period (PR = 0.998, [95% CIs: 0.996, 1.000]; p = 0.029). Among those aged 16-24 years, a significant decreasing trend in the month-to-month prevalence ratio was found in the post- compared to pre-December 2014 intervention period (PR = 0.991, [95% CIs: 0.984, 0.998];p <0.01). A marginal effect was observed in the post- compared to pre-April 2018 intervention period for those aged 25-34 years (PR = 0.996, [95% CIs: 0.992, 1.000]; p = 0.048)., Conclusion: Although no evidence of change was observed following the December 2014 intervention period, a significant decline in the prevalence ratio of valproate use was observed after the 2018 intervention, which may reflect the introduction of the most recent contraindication measures., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objectives: To establish awareness, knowledge, use and experience in practice of a sodium valproate pregnancy prevention program (PPP) in Ireland ("prevent") among three healthcare professional (HCP) groups., Methods: A cross-sectional study using anonymous online surveys was conducted among general practitioners (GPs), pharmacists, and specialist consultants. Descriptive analyses are presented., Results: HCP response rates were 5.8% for GPs (90/1544), 10.7% for pharmacists (219/2052), and 7.6% for specialists (17/224). Across HCP groups, there was high awareness (>90%) for specialist referral when female valproate patients are planning pregnancy, or become pregnant, but less awareness to refer annually for specialist review. While awareness of a possible teratogenic effect at any stage of pregnancy was high (>80%), most GPs (62.2%, 95% CI: 51.3, 71.9%) and community pharmacists (53.1%, 95% CI: 43.2, 62.8%) were unsure of the magnitude of risk for developmental disorders, while most specialists under-estimated this risk (46.7%, 95% CI: 24.8, 69.9%). Although >70% of the respondents identified valproate to be contraindicated in any woman of childbearing potential unless the conditions of the PPP are fulfilled, experience implementing key elements in practice varied., Conclusions: Our findings suggest continued effort is needed to ensure optimal implementation of "prevent" into clinical practice in Ireland.

Objective: Despite rapid declines over the last two decades, coronary heart disease (CHD) mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland., Methods: CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year) to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by 2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and (iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted., Results: Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84). In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8-9.0%. These projections remained stable under a wide range of sensitivity analyses., Conclusions: Feasible reductions in four cardiovascular risk factors (already achieved elsewhere) could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity.

Objectives: The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches., Methods: Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality., Results: The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease., Conclusions: The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)