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.

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.

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.

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.

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.

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.

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.

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.

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.

Cross-sectional questionnaire study of the experiences of community pharmacists in Northern Ireland during the early phases of the COVID-19 pandemic: preparation, experience and response.

OBJECTIVES: To examine the views and experiences of community pharmacists in Northern Ireland (NI) regarding changes in community pharmacy practice/processes in preparation for, and response to, the COVID-19 pandemic. DESIGN: Cross-sectional telephone-administered questionnaire. SETTING AND PARTICIPANTS: Geographically stratified representative sample of 130 community pharmacists in NI between March and May 2021. OUTCOME MEASURES: Community pharmacists' responses to questions focusing on their preparation, experience and response to the COVID-19 pandemic. Descriptive analysis was conducted including frequencies and percentages. Free-text comments were summarised using thematic analysis. RESULTS: One hundred and thirty pharmacists completed the questionnaire. Pharmacists responded comprehensively to implementing infection control measures, for example, management of social distancing in the shop (96.2%), making adjustments to premises, for example, barriers/screens (95.4%), while maintaining medicines supply (100.0%) and advice to patients (93.1%). Newly commissioned services were provided, for example, emergency supply service (93.1%), influenza vaccination for healthcare workers (77.7%) and volunteer deliveries to vulnerable people (54.6%). Pharmacists were least prepared for the increased workload and patients' challenging behaviour, but the majority (96.9%) reported that they felt better prepared during the second wave. Pharmacists agreed/strongly agreed that they would be able to re-establish normal services (87.7%), were willing to administer COVID-19 vaccines (80.7%) and provide COVID-19 testing (60.8%) in the future. CONCLUSIONS: Community pharmacists remained accessible and maintained supply of essential medicines and advice to patients throughout the pandemic. Provision of modified and additional services such as vaccination reinforced the clinical and public health role of pharmacy.

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.

Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017.

OBJECTIVE: To examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017. DESIGN: Repeated cross-sectional study. SETTING: Drug poisoning deaths in Ireland. PARTICIPANTS: National Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017. OUTCOME MEASURES: The primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004-2017), change points over time and average annual percentage changes (AAPCs) with 95% CI. RESULTS: Increased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3). CONCLUSION: Drugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.

Systematic Comparison of Biomaterials-Based Strategies for Osteochondral and Chondral Repair in Large Animal Models.

Joint repair remains a major challenge in orthopaedics. Recent progress in biomaterial design has led to the fabrication of a plethora of promising devices. Pre-clinical testing of any joint repair strategy typically requires the use of large animal models (e.g., sheep, goat, pig or horse). Despite the key role of such models in clinical translation, there is still a lack of consensus regarding optimal experimental design, making it difficult to draw conclusions on their efficacy. In this context, the authors performed a systematic literature review and a risk of bias assessment on large animal models published between 2010 and 2020, to identify key experimental parameters that significantly affect the biomaterial therapeutic outcome and clinical translation potential (including defect localization, animal age/maturity, selection of controls, cell-free versus cell-laden). They determined that mechanically strong biomaterials perform better at the femoral condyles; while highlighted the importance of including native tissue controls to better evaluate the quality of the newly formed tissue. Finally, in cell-laded biomaterials, the pre-culture conditions played a more important role in defect repair than the cell type. In summary, here they present a systematic evaluation on how the experimental design of preclinical models influences biomaterial-based therapeutic outcomes in joint repair.

Awareness, knowledge and practice of healthcare professionals following implementation of a Pregnancy Prevention Program for sodium valproate in Ireland: a multi-stakeholder cross-sectional study.

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.

Underlying conditions and risk of hospitalisation, ICU admission and mortality among those with COVID-19 in Ireland: A national surveillance study.

BACKGROUND: To date, over 2 million people worldwide have died with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To describe the experience in Ireland, this study examined associations between underlying conditions and the following outcomes: mortality, admission to hospital or admission to the intensive care unit (ICU) among those infected with COVID-19. METHODS: This study used data from the Health Protection Surveillance Centre in Ireland and included confirmed cases of COVID-19 from the first wave of the pandemic between March and July 2020. Two cohorts were included: all cases (community and hospital) and hospital admissions only. For all cases, health outcome data included mortality and hospitalisation. For hospitalised cases, outcome data included mortality and ICU admission. Logistic regression was used to examine associations between underlying conditions and outcomes across both cohorts. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CIs). FINDINGS: There were 19,789 cases included in analysis, which encompassed 1,476 (7.5%) deaths, 2,811 (14.2%) hospitalisations, and 438 (2.2%) ICU admissions of whom 90 (20.5%) died. Significantly higher risk of mortality, hospitalisation and ICU admission was associated with having chronic heart disease, a BMI ≥40kg/m2 and male sex. Additionally, diagnosis of a chronic neurological condition (OR 1.41; 95%CI:1.17, 1.69), chronic kidney disease (OR 1.74; 95%CI:1.35, 2.24) and cancer (OR 2.77; 95%CI:2.21, 3.47) were significantly associated with higher risk of mortality among all cases, with similar patterns of association observed for mortality among hospitalised cases. INTERPRETATION: The identification of underlying conditions among COVID-19 cases may help identify those at highest risk of the worst health outcomes and inform preventive strategies to improve outcomes. FUNDING: This study was supported by the Health Service Executive, Health Protection Surveillance Centre. KEB and MM are funded by the Health Research Board (RL-15-1579 and EIA-2019-012 respectively).

The StrokeCog study: development and description of a cognition-focused psychological intervention to address cognitive impairment following stroke.

OBJECTIVE: To describe the process of developing a cognitive rehabilitation intervention for patients with post-stroke cognitive impairment (PSCI) and to describe the intervention prior to evaluation in a pilot randomised controlled trial (RCT). Method: The Medical Research Council framework, 'Developing and evaluating complex interventions', was used to develop the cognitive rehabilitation intervention. We conducted a combined analysis of the existing evidence base for PSCI rehabilitation alongside qualitative exploration of the perspectives of stroke survivors, their families, and healthcare professionals providing stroke care, on the necessary components for a cognitive rehabilitation intervention for PSCI. The Template for Intervention Description and Replication checklist was used as a structural framework for the description of the intervention. Results: The intervention comprises a five-week intervention integrating group-based activities, supported by a clinical neuropsychologist, with home-based activities to encourage self-efficacy through the practice of adjustment and compensatory strategies learned in the group format to achieve the patients' identified goals in managing their PSCI. Conclusion: A cognitive rehabilitation intervention for patients with PSCI has been developed and described. We are in the process of developing a structured intervention manual to standardise the content and delivery of the intervention for further testing in a pilot RCT.

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 Prevalence of Cognitive Impairment on Admission to Nursing Home among Residents with and without Stroke: A Cross-Sectional Survey of Nursing Homes in Ireland.

Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Epidemiological evidence indicates that, with an ageing population, stroke and PSCI are likely to increase in the coming decades. This may have considerable implications for the demand for nursing home placement. As prevalence estimates of both cognitive impairment and dementia on admission to nursing home among residents with and without stroke have not yet been compared, they were estimated and compared in this study. We performed a cross-sectional survey to establish the admission characteristics of 643 residents in 13 randomly selected nursing homes in Ireland. The survey collected data on resident's stroke and cognitive status at the time of nursing home admission. The survey found, among nursing home residents that experienced stroke prior to admission, prevalence estimates for cognitive impairment (83.8%; 95% CI = 76.9-90.6%) and dementia (66.7%; 95% CI = 57.9-75.4%) were significantly higher compared to residents that had not experienced stroke prior to admission (cognitive impairment: 56.6%; 95% CI = 52.4-60.8%; X2 (1) = 28.64; p < 0.001; dementia: 49.8%; 95% CI = 45.6-54.1%; X2 (1) = 10.47; p < 0.01). Since the prevalence of PSCI is likely to increase in the coming decades, the findings highlight an urgent need for health service planning for this increased demand for nursing home care to meet the care needs of these stroke survivors.