Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort.

BACKGROUND: Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors. METHODS: We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription. RESULTS: CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. CONCLUSION: CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

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.

Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study.

INTRODUCTION: Problematic polypharmacy is the prescribing of five or more medications potentially inappropriately. Unintentional prescribing cascades represent an under-researched aspect of problematic polypharmacy and occur when an adverse drug reaction (ADR) is misinterpreted as a new symptom resulting in the initiation of a new medication. The aim of this study was to elicit key stakeholders' perceptions of and attitudes towards problematic polypharmacy, with a focus on prescribing cascades. METHODS: qualitative one-to-one semi-structured interviews were conducted with predefined key stakeholder groups. Inductive thematic analysis was employed. RESULTS: Thirty-one stakeholders were interviewed: six patients, two carers, seven general practitioners, eight pharmacists, four hospital doctors, two professional organisation representatives and two policymakers. Three main themes were identified: (i) ADRs and prescribing cascades-a necessary evil. Healthcare professionals (HCPs) expressed concern that experiencing an ADR would negatively impact patients' confidence in their doctor. However, patients viewed ADRs pragmatically as an unpredictable risk. (ii) Balancing the risk/benefit tipping point. The complexity of prescribing decisions in the context of polypharmacy made balancing this tipping point challenging. Consequently, HCPs avoided medication changes. (iii) The minefield of medication reconciliation. Stakeholders, including patients and carers, viewed medication reconciliation as a perilous activity due to systemic communication deficits. CONCLUSION: Stakeholders believed that at a certain depth of polypharmacy, the risk that a new symptom is being caused by an existing medication becomes incalculable. Therefore, in the absence of harm, medication changes were avoided. However, medication reconciliation post hospital discharge compelled prescribing decisions and was seen as a high-risk activity by stakeholders.

Pediatric blood cultures-turning up the volume: a before and after intervention study.

The major determinant of blood culture (BC) diagnostic performance is blood volume, and pediatric sample volumes are frequently low. We aimed to assess BC volumes in our institution, design an intervention to increase volumes, and assess its impact. All pediatric BCs submitted over a 7-month period to the microbiology laboratory in a university hospital (including emergency department, pediatric ward, and neonatal unit) were included. A pre-intervention period assessed current practice. A multi-faceted intervention (education, guideline introduction, active feedback strategies) was collaboratively designed by all stakeholders. Impact was assessed in a post-intervention period. The main outcome measures included the percentage of samples adequately filled using three measures of sample adequacy (1) manufacturer-recommended minimum validated volume-> 0.5 ml, (2) manufacturer-recommended optimal minimum volume-> 1.0 ml, (3) newly introduced age-specific recommendations. Three hundred ninety-eight pre-intervention and 388 post-intervention samples were included. Initial volumes were low but increased significantly post-intervention (median 0.77 ml vs. 1.52 ml), with multivariable regression analysis estimating volumes increased 89% post-intervention. There were significant increases in all measures of volume adequacy, including an increase in age-appropriate filling (20.4-53.1%), with less improvement in those aged > 3 years. Overall, 68.4% of pathogens were from adequately filled cultures, while 76% of contaminants were from inadequately filled cultures. A pathogen was detected in a higher proportion of adequately filled than inadequately filled cultures (9.4% vs. 2.2%, p < 0.001).  Conclusion: Blood volume impacts BC sensitivity, with lower volumes yielding fewer pathogens and more contaminants. Focused intervention can significantly improve volumes to improve diagnostic performance. What is Known: • Blood volume is the major determinant of blood culture positivity, and yet pediatric blood culture volumes are frequently low, resulting in missed pathogens and increased contamination. What is New: • Adequately filled (for age) blood cultures have a pathogen detection rate three times higher than inadequately filled blood cultures. • This interventional study shows that collaboratively designed multi-modal interventions including focus on accurate volume measurement can lead to significant increases in blood volumes and improve blood culture diagnostic performance.

The Development of Principles for Patient and Public Involvement (PPI) in Preclinical Spinal Cord Research: A Modified Delphi Study.

INTRODUCTION: There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence-informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. METHODS: This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty-eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. RESULTS: Thirty-eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. CONCLUSION: This research developed a previously unavailable set of evidence-informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. PATIENT AND PUBLIC INVOLVEMENT STATEMENT: This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co-authors.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland.

INTRODUCTION: The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. RESULTS: A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). CONCLUSION: Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.

The impact of lidocaine plaster prescribing reduction strategies: A comparison of two national health services in Europe.

AIMS: In 2017, two distinct interventions were implemented in Ireland and England to reduce prescribing of lidocaine medicated plasters. In Ireland, restrictions on reimbursement were introduced through implementation of an application system for reimbursement. In England, updated guidance on items which should not be routinely prescribed in primary care, including lidocaine plasters, was published. This study aims to compare how the interventions impacted prescribing of lidocaine plasters in these countries. METHODS: We conducted an interrupted time-series study using general practice data. For Ireland, monthly dispensing data (2015-2019) from the means-tested General Medical Services (GMS) scheme was used. For England, data covered all patients. Outcomes were the rate of dispensings, quantity and costs of lidocaine plasters, and we modelled level and trend changes from the first full month of the policy/guidance change. RESULTS: Ireland had higher rates of lidocaine dispensings compared to England throughout the study period; this was 15.22/1000 population immediately pre-intervention, and there was equivalent to a 97.2% immediate reduction following the intervention. In England, the immediate pre-intervention dispensing rate was 0.36/1000, with an immediate reduction of 0.0251/1000 (a 5.8% decrease), followed by a small but significant decrease in the monthly trend relative to the pre-intervention trend of 0.0057 per month. CONCLUSIONS: Among two different interventions aiming to decrease low-value lidocaine plaster prescribing, there was a substantially larger impact in Ireland of reimbursement restriction compared to issuing guidance in England. However, this is in the context of much higher baseline rates of use in Ireland compared to England.

Recruiting general practitioners and older patients with multimorbidity to randomized trials.

BACKGROUND: Older patients with multimorbidity are under-represented in experimental research. OBJECTIVE: To explore the barriers and facilitators to general practitioner (GP) and older patient recruitment and retention in a cluster randomized controlled trial (RCT). METHOD: This descriptive study uses qualitative and quantitative data from a cluster RCT, designed to evaluate the effectiveness of a medicines optimization intervention. The SPPiRE cluster RCT enrolled 51 general practices and 404 patients aged ≥65 years and prescribed ≥15 medicines. Quantitative data were collected from all recruited practices and 32 additional practices who were enrolled, but unable to recruit sufficient participants. Qualitative data were collected from purposive samples of intervention GPs (18/26), patients (27/208), and researcher logs and analysed thematically using inductive coding. RESULTS: Enrolment rates for practices and patients were 37% and 25%, respectively. Barriers to GP recruitment were lack of resources and to patient recruitment were difficulty understanding trial material and concern about medicines being taken away. GPs' primary motivation was perceived importance of the research question, whereas patients' primary motivation was trust in their GP. All general practices were retained. Thirty-five patients (8.6%) were lost to follow-up for primary outcomes, mainly because they had died and 45% did not return patient-reported outcome measures (PROMs). CONCLUSION: Patient retention for the primary outcome was high, as it was collected directly from patient records. Patient completion of PROM data was poor, reflecting difficulty in understanding trial material. Recruiting older patients with multimorbidity to clinical trials is possible but requires significant resource and planning. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12752680.

Randomized controlled trials (RCTs) often exclude older people with multiple medical conditions. The aim of this study was to explore how and why participants took part in a primary care based RCT that included 51 general practitioners (GPs) and 404 older patients prescribed ≥15 medicines. The RCT was designed to assess the usefulness of a supported medication review. The study team assessed information that was already collected as part of the RCT, to describe the process of inviting and enrolling GPs and older people. This included information on the numbers invited and enrolled and interviews from a smaller sample of GPs (18) and older people (27). The study successfully enrolled the required number of participants but it took 26 months more than planned. 37% of invited GPs and 25% of invited patients took part. GPs felt the research was important but they identified lack of time and resources as barriers to participation. Older people predominantly took part because they trusted their GP but some were wary of having medicines taken away and were put off by trial documentation. It is important that RCTs including older people with multiple medical conditions carefully plan recruitment and pay careful attention to trial documentation.

Prescribing differences among older adults with differing health cover and socioeconomic status: a cohort study.

INTRODUCTION: As health reforms move Ireland from a mixed public-private system toward universal healthcare, it is important to understand variations in prescribing practice for patients with differing health cover and socioeconomic status. This study aims to determine how prescribing patterns for patients aged ≥ 65 years in primary care in Ireland differ between patients with public and private health cover. METHODS: This was an observational study using anonymised data collected as part of a larger study from 44 general practices in Ireland (2011-2018). Data were extracted from electronic records relating to demographics and prescribing for patients aged ≥ 65 years. The cohort was divided between those with public health cover (via the General Medical Services (GMS) scheme) and those without. Standardised rates of prescribing were calculated for pre-specified drug classes. We also analysed the number of medications, polypharmacy, and trends over time between groups, using multilevel linear regression adjusting for age and sex, and hospitalisations. RESULTS: Overall, 42,456 individuals were included (56% female). Most were covered by the GMS scheme (62%, n = 26,490). The rate of prescribing in all drug classes was higher for GMS patients compared to non-GMS patients, with the greatest difference in benzodiazepine anxiolytics. The mean number of unique medications prescribed to GMS patients was 10.9 (SD 5.9), and 8.1 (SD 5.8) for non-GMS patients. The number of unique medications prescribed to both GMS and non-GMS cohorts increased over time. The increase was steeper in the GMS group where the mean number of medications prescribed increased by 0.67 medications/year. The rate of increase was 0.13 (95%CI 0.13, 0.14) medications/year lower for non-GMS patients, a statistically significant difference. CONCLUSION: Our study found a significantly larger number of medications were prescribed to patients with public health cover, compared to those without. Increasing medication burden and polypharmacy among older adults may be accelerated for those of lower socioeconomic status. These findings may inform planning for moves towards universal health care, and this would provide an opportunity to evaluate the effect of expanding entitlement on prescribing and medications use.

Survival in an era of organ preservation: an update on laryngeal cancer in Ireland.

BACKGROUND: Laryngeal cancer epidemiology has changed in recent years, with falling incidence observed internationally. Organ preservation therapies have revolutionised management, though some patients may be unsuitable and survival was noted to fall in the 2000s. This study examines trends in laryngeal cancer in Ireland. METHODS: A retrospective cohort study of National Cancer Registry of Ireland data from 1994 to 2014. RESULTS: From a cohort of 2651, glottic disease was most common (62%, n = 1646). Incidence rose to 3.43 cases/100,000/year for 2010-2014. 5-year disease-specific survival (DSS) was 60.6% and did not change significantly over time. Overall survival (OS) for T3 disease managed with primary radiotherapy was similar to primary surgery (HR 0.98, p = 0.9). DSS for T3 disease improved with primary radiotherapy (HR 0.72, p = 0.045). CONCLUSION: Incidence of laryngeal cancer in Ireland rose despite international trends, while survival changed little. Radiotherapy improves DSS for T3 disease but does not improve OS, possibly secondary to poor organ function post-radiotherapy.

GP-delivered medication review of polypharmacy, deprescribing, and patient priorities in older people with multimorbidity in Irish primary care (SPPiRE Study): A cluster randomised controlled trial.

BACKGROUND: There is a rising prevalence of multimorbidity, particularly in older patients, and a need for evidence-based medicines management interventions for this population. The Supporting Prescribing in Older Adults with Multimorbidity in Irish Primary Care (SPPiRE) trial aimed to investigate the effect of a general practitioner (GP)-delivered, individualised medication review in reducing polypharmacy and potentially inappropriate prescriptions (PIPs) in community-dwelling older patients with multimorbidity in primary care. METHODS AND FINDINGS: We conducted a cluster randomised controlled trial (RCT) set in 51 GP practices throughout the Republic of Ireland. A total of 404 patients, aged ≥65 years with complex multimorbidity, defined as being prescribed ≥15 regular medicines, were recruited from April 2017 and followed up until October 2020. Furthermore, 26 intervention GP practices received access to the SPPiRE website where they completed an educational module and used a template for an individualised patient medication review that identified PIP, opportunities for deprescribing, and patient priorities for care. A total of 25 control GP practices delivered usual care. An independent blinded pharmacist assessed primary outcome measures that were the number of medicines and the proportion of patients with any PIP (from a predefined list of 34 indicators based predominantly on the STOPP/START version 2 criteria). We performed an intention-to-treat analysis using multilevel modelling. Recruited participants had substantial disease and treatment burden at baseline with a mean of 17.37 (standard deviation [SD] 3.50) medicines. At 6-month follow-up, both intervention and control groups had reductions in the numbers of medicines with a small but significantly greater reduction in the intervention group (incidence rate ratio [IRR] 0.95, 95% confidence interval [CI]: 0.899 to 0.999, p = 0.045). There was no significant effect on the odds of having at least 1 PIP in the intervention versus control group (odds ratio [OR] 0.39, 95% CI: 0.140 to 1.064, p = 0.066). Adverse events recorded included mortality, emergency department (ED) presentations, and adverse drug withdrawal events (ADWEs), and there was no evidence of harm. Less than 2% of drug withdrawals in the intervention group led to a reported ADWE. Due to the inability to electronically extract data, primary outcomes were measured at just 2 time points, and this is the main limitation of this work. CONCLUSIONS: The SPPiRE intervention resulted in a small but significant reduction in the number of medicines but no evidence of a clear effect on PIP. This reduction in significant polypharmacy may have more of an impact at a population rather than individual patient level. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12752680.

Cost outcomes of potentially inappropriate prescribing in middle-aged adults: A Delphi consensus and cross-sectional study.

BACKGROUND: Potentially inappropriate prescribing (PIP) is common in older adults and is associated with increased medication costs and costs of associated adverse drug events. PIP also affects almost 1/5 of middle-aged adults (45-64 y), as defined by the PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria. However, there has been little research on PIP medication costs within this age group. AIMS: Calculate the medication costs of PIP for middle-aged adults according to the 22 PROMPT criteria and compare with the cost of consensus-validated, evidence-based (adequate) alternative prescribing scenarios. METHODS: Adequate alternatives to the 22 PROMPT criteria were created via literature review. A Delphi consensus panel of experts was recruited (n = 16), supported by a patient and public involvement group, to achieve consensus on the alternatives. A retrospective repeated cross-sectional study from 2014 to 2019 was then conducted utilising pseudonymised primary care data from Lambeth DataNet in South London (41 general practices, n = 1 185 335, using Lambeth DataNet May 2020 extract) to calculate the cost of PIP. RESULTS: The cross-sectional study included 55 880 patients. The total PIP cost was £2.79 million, with adequate alternative prescribing costing £2.74 million (cost savings of £51 278). Duplicate drug classes was the most costly criterion for both PIP and alternative prescribing. CONCLUSION: This study calculated the medication costs of PIP and created alternative prescribing scenarios for the 22 PROMPT criteria. There is no substantial cost difference between adequate prescribing vs. PIP. Future studies should investigate the wider health economic costs of alternative prescribing, such as reducing hospital admissions.

Patient and general practitioner experiences of implementing a medication review intervention in older people with multimorbidity: Process evaluation of the SPPiRE trial.

INTRODUCTION: The SPPiRE cluster randomized controlled trial found that a general practitioner (GP)-delivered medication review that incorporated screening for potentially inappropriate prescriptions (PIP), a brown bag review and a patient priority assessment, resulted in a significant but small reduction in the number of medicines and no significant reduction in PIP. This process evaluation aims to explore the experiences of GPs and patients and the potential for system-wide implementation. METHODS: The trial included 51 general practices and 404 participants with multimorbidity aged ≥65 years, prescribed ≥15 medicines. The process evaluation used mixed methods and ran parallel to the trial. Quantitative data was collected from the SPPiRE intervention website and analysed descriptively. Qualitative data on medication changes were collected from intervention GPs (18/26) and a purposive sample of intervention patients (27/208) via semi-structured telephone interviews. All interviews were transcribed verbatim and analysed using a thematic analysis. Qualitative and quantitative data were integrated using a triangulation protocol. RESULTS: The analysis generated two themes, intervention implementation and mechanisms of action, and both were underpinned by the theme of context. Intervention delivery varied among practices and 45 patients (28%) had no review, primarily due to insufficient GP time. 80% of reviewed patients had ≥1 PIP identified, 59% had ≥1 problem identified during the brown bag review and 79% had ≥1 priority recorded. The brown bag review resulted in the most deprescription of medications. GPs and patients responded positively to the intervention but most GPs did not engage with the patient priority-setting process. GPs identified a lack of integration into practice software and resources as barriers to future implementation. CONCLUSION: The SPPiRE intervention had a small effect in reducing the number of medicines and this was primarily mediated through the brown bag review. The context of resource shortages and deep-seated views around medical decision-making influenced intervention implementation. PATIENT OR PUBLIC CONTRIBUTION: Qualitative data on the implementation of the medication review and their wider views on their medicines was collected from older people with multimorbidity through semi-structured telephone interviews. CLINICAL TRIAL REGISTRATION: The SPPiRE trial was registered prospectively on the ISRCTN registry (ISRCTN12752680).

Applying Patient and Public Involvement in preclinical research: A co-created scoping review.

BACKGROUND: Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence-based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects. METHODS: A scoping review was conducted to search the literature in Medline (PubMed), EMBASE, CINAHL, PsycInfo and Web of Science Core Collection to identify applied examples of preclinical PPI. Two independent reviewers conducted study selection and data extraction separately. Data were extracted relating to PPI in terms of (i) rationale and aims, (ii) approach used, (iii) benefits and challenges, (iv) impact and evaluation and (v) learning opportunities for preclinical PPI. Findings were reviewed collaboratively by PPI contributors and the research team to identify principles that could be applied to other projects. RESULTS: Nine studies were included in the final review with the majority of included studies reporting PPI to improve the relevance of their research, using approaches such as PPI advisory panels and workshops. Researchers report several benefits and challenges, although evidence of formal evaluation is limited. CONCLUSION: Although currently there are few examples of preclinical research studies reporting empirical PPI activity, their findings may support those aiming to use PPI in preclinical research. Through collaborative analysis of the scoping review findings, several principles were developed that may be useful for other preclinical researchers. PATIENT OR PUBLIC CONTRIBUTION: This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5-year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers and PPI facilitators collaborated as co-authors on the conceptualization, execution and writing of this review, including refining the findings into the set of principles reported here.

Investigation of the role of sleep and physical activity for chronic disease prevalence and incidence in older Irish adults.

BACKGROUND: Chronic diseases are the leading cause of death worldwide. Many of these diseases have modifiable risk factors, including physical activity and sleep, and may be preventable. This study investigated independent associations of physical activity and sleep with eight common chronic illnesses. METHODS: Data were from waves 1, 3 and 5 of The Irish Longitudinal Study on Ageing (n = 5,680). Inverse probability weighted general estimating equations were used to examine longitudinal lifetime prevalence and cumulative incidence of self-reported conditions. RESULTS: Sleep problems were significantly associated with increased odds of incident and prevalent arthritis and angina. Additionally sleep problems were associated with higher odds of lifetime prevalence of hypertension and diabetes. Physical activity was negatively associated incident osteoporosis and respiratory diseases and negatively associated with lifetime prevalence of hypertension, high cholesterol and diabetes. CONCLUSIONS: Worse sleep quality and lower physical activity were associated with higher odds of chronic diseases. Interventions to improve sleep and physical activity may improve health outcomes.

The changing face of Irish head and neck cancer epidemiology: 20 years of data.

BACKGROUND: Head and neck cancer (HNC) is associated with significant morbidity and mortality, especially when high stage disease is present. The epidemiology and prognosis of HNC has changed considerably over the last 20 years. AIMS: This study aimed to examine the epidemiological trends in HNC patients over a prolonged period in Ireland. METHODS: We conducted a retrospective cohort study using 20 years of cancer registry data provided by the National Cancer Registry of Ireland. Baseline characteristics and survival statistics were thereby generated. RESULTS: 10,148 patients were identified. There is a growing population of young (< 50 years) and very old (> 85 years) HNC patients; 48.15% of the population was elderly (> 65 years). Oral cavity (29.8%) and laryngeal cancer (28.1%) remain the most prevalent subsites, though oral cavity cancer prevalence declined from 35.9% in 1994 to 27.5% in 2014. Oropharyngeal cancer prevalence increased from 13.6 to 22.2% over the same period. Overall 5-year survival has improved significantly to 56.8% in 2010 but there remains a disparity between the elderly and adult cohorts (42.0% vs 60.7%). 5-year survival for hypopharyngeal and oropharyngeal cancers has improved from 11.8% and 33.3% to 22.2% and 44.8%, respectively, while laryngeal and oral cavity cancer survival remains approximately stable at 58.7% and 61.5%, respectively. CONCLUSION: HNC survival in Ireland has improved in line with increasing recognition of the value of multidisciplinary assessment, subspecialisation in cancer care, and targeted therapies based on tumour subsites. Survival in the elderly cohort remains poor despite increasing recognition of the challenges such cases pose.

Cognitive decline associated with anticholinergics, benzodiazepines and Z-drugs: Findings from The Irish Longitudinal Study on Ageing (TILDA).

AIMS: To estimate the association between patterns of anticholinergic, benzodiazepine and Z-drug medication use and change in cognitive function in middle-aged and older adults. METHODS: This prospective cohort study used data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), including community-dwelling adults aged ≥50 years followed for up to 4 years (n = 7027). Cognitive function was assessed using the Mini Mental State Examination, animal naming test and word recall tests. Regular medication use was self-reported at baseline and follow-up interviews at 2 and 4 years. Pharmacy dispensing claims for a subset (n = 2905) allowed assessment of medication use between interviews and cumulative dosage. Medication use at consecutive waves of TILDA was analysed in relation to change in cognitive function between waves. RESULTS: Strongly anticholinergic medications (Anticholinergic Cognitive Burden scale 3), benzodiazepines and Z-drugs were reported by 7.3%, 5.8% and 5.1% of participants, respectively, at any time during the study. Adjusting for potential confounders, new anticholinergic use between interviews was associated with change in recall score (-1.09, 95% confidence interval -1.64, -0.53) over 2 years compared to non-use, but not with MMSE (0.07; 95% CI -0.21, 0.34) or animal naming (-0.70; 95% CI -1.43, 0.03). The pharmacy claims analysis was consistent with this finding. Other hypothesised associations were not supported. CONCLUSIONS: Except for new use of anticholinergic medications, no other findings supported a risk of cognitive decline over 2-year periods in this middle-aged and older cohort. Patients and prescribers should weigh this potential risk against potential benefits of commencing anticholinergic medications.

Aspirin prescribing for cardiovascular disease in middle-aged and older adults in Ireland: Findings from The Irish Longitudinal Study on Ageing.

Aspirin use for cardiovascular indications is widespread despite evidence not supporting use in patients without cardiovascular disease (CVD). This study characterises aspirin prescribing among people aged ≥50 years in Ireland for primary and secondary prevention, and factors associated with prescription. This cross-sectional study includes participants from wave 3 (2014-2015) of The Irish Longitudinal Study on Ageing. We identified participants reporting use of prescribed aspirin, other antiplatelets/anticoagulants, and doctor-diagnosed CVD (MI, angina, stroke, TIA) and other cardiovascular conditions. We examined factors associated with aspirin use for primary and secondary prevention in multivariate regression. For a subset, we also examined 10-year cardiovascular risk (using the Framingham general risk score) as a predictor of aspirin use. Among 6618 participants, the mean age was 66.9 years (SD 9.4) and 55.6% (3679) were female. Prescribed aspirin was reported by 1432 participants (21.6%), and 77.6% of aspirin users had no previous CVD. Among participants with previous CVD, 16.5% were not prescribed aspirin/another antithrombotic. This equates to 201,000 older adults nationally using aspirin for primary prevention, and 16,000 with previous CVD not prescribed an antithrombotic. Among those without CVD, older age, male sex, free health care, and more GP visits were associated with aspirin prescribing. Cardiovascular risk was significantly associated with aspirin use (adjusted relative risk 1.15, 95%CI 1.08-1.23, per 1% increase in cardiovascular risk). Almost four-fifths of people aged ≥50 years on aspirin have no previous CVD, equivalent to 201,000 adults nationally, however prescribing appears to target higher cardiovascular risk patients.

Factors associated with initiation of bone-health medication among older adults in primary care in Ireland.

BACKGROUND: Adults at high risk of fragility fracture should be offered pharmacological treatment when not contraindicated, however, under-treatment is common. OBJECTIVE: This study aimed to investigate factors associated with bone-health medication initiation in older patients attending primary care. DESIGN: This was a retrospective cohort study. SETTING: The study used data from forty-four general practices in Ireland from 2011-2017. SUBJECTS: The study included adults aged ≥ 65 years who were naïve to bone-health medication for 12 months. METHODS: Overall fracture-risk (based on QFracture) and individual fracture-risk factors were described for patients initiated and not initiated onto medication and compared using generalised linear model regression with the Poisson distribution. RESULTS: Of 36,799 patients (51% female, mean age 75.4 (SD = 8.4)) included, 8% (n = 2,992) were observed to initiate bone-health medication during the study. One-fifth of all patients (n = 8,193) had osteoporosis or had high fracture-risk but only 21% of them (n = 1,687) initiated on medication. Female sex, older age, state-funded health cover and osteoporosis were associated with initiation. Independently of osteoporosis and co-variates, high 5-year QFracture risk for hip (IRR = 1.33 (95% CI = 1.17-1.50), P < 0.01) and all fractures (IRR = 1.30 (95% CI = 1.17-1.44), P < 0.01) were associated with medication initiation. Previous fracture, rheumatoid arthritis and corticosteroid use were associated with initiation, while liver, kidney, cardiovascular disease, diabetes and oestrogen-only hormone replacement therapy showed an inverse association. CONCLUSIONS: Bone-health medication initiation is targeted at patients at higher fracture-risk but much potential under-treatment remains, particularly in those >80 years and with co-morbidities. This may reflect clinical uncertainty in older multimorbid patients, and further research should explore decision-making in preventive bone medication prescribing.

Vaccine hesitancy and reported non-vaccination in an Irish pediatric outpatient population.

Vaccine hesitancy is defined as a delay in acceptance, or refusal, of vaccines, despite availability. It is a complex and context specific phenomenon and identified as a global health priority. The "Parent Attitudes about Childhood Vaccines" (PACV) questionnaire is a validated tool for identifying vaccine hesitancy. Our aim was to use the PACV to assess vaccine hesitancy and its relationship with reported non-vaccination in an Irish population, for the first time. Our participants were parents or caregivers of children attending general pediatric clinics in a tertiary pediatric hospital in Dublin, Ireland, between September and December 2018. In total, 436 participants completed the questionnaire. 5.5% of our population reported non-vaccination. Human papilloma virus and measles, mumps, rubella vaccines were the most commonly cited vaccines of concern (11.5% and 6.7%, respectively), and autism spectrum disorder was the most commonly side effect of concern (4.3%). Mean PACV score was 26.9 (SD 19.1), with a significant difference between non-vaccinators and vaccinators (53.2 vs 25.3, p<0.001). Safety and efficacy concerns were the major contributor to non-vaccination. 14.4% of our population were vaccine-hesitant using the conventional cut-off score, which increased to 22% when using an optimal cut-off which maximized sensitivity and specificity. The accuracy of the PACV score to identify non-vaccination was good (area under the ROC curve = 0.827), and the optimal cut-off had a high negative predictive value (98.5%).Conclusion: PACV identified reported non-vaccination with high accuracy in our population. It may be useful to screen vaccine-hesitant parents who could benefit from interventions to improve uptake. What is Known: • Vaccine hesitancy is a leading threat to global health, with falls in vaccine uptake associated with disease outbreaks worldwide. • The Parent Attitudes about Childhood Vaccines (PACV) questionnaire is a validated measure of vaccine hesitancy and correlates with non-vaccination in many populations. What is New: • This large study in a pediatric outpatient clinic setting represents the first use of the PACV in a Western European population to assess vaccination hesitancy. • The PACV may be an effective way of screening a pediatric clinic population to identify vaccine-hesitant parents or caregivers for targeted vaccine promotion.