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Background: Credentialing of advanced and specialist pharmacist practice (ASPP) provides essential quality assurance for ASPP, which is significantly different to entry-level practice and is developing worldwide. Several credentialing models are in place or under development internationally. Synthesis of the views and experiences of pharmacists and other relevant stakeholders on credentialing is an important research gap. Objective(s): To determine pharmacy stakeholders' views and experiences of ASPP credentialing and to explore facilitators and barriers to credentialing implementation and uptake. Methods: The Joanna Briggs Institute convergent integrated approach for mixed methods systematic reviews was followed. The review protocol was pre-registered with PROSPERO. Five electronic databases (Medline, CINAHL, Embase, Web of Science, Google Scholar) were searched from inception to August 2022 for qualitative, quantitative, or mixed methods studies that reported the views and experiences of pharmacy stakeholders on ASPP credentialing. The Mixed Methods Appraisal Tool was used to quality appraise included studies. Thematic synthesis was undertaken to analyse and integrate data from included studies. All screening and data analysis steps were performed by two reviewers independently, with additional author input where required. Results: Sixty studies were included, after screening titles and abstracts (n = 9055) and full texts (n = 228). Studies represented the views of pharmacists, pharmacy managers/employers and professional/representative bodies in hospital, community pharmacy, general practice/primary care, and academic sectors, from 40 countries. Four analytical themes were generated describing the factors, including facilitators and barriers, to be considered when developing or optimising ASPP credentialing: I. Drivers of credentialing, II. Developing ASPP competence, III. Optimising credentialing implementation, and IV. Enhancing credentialing uptake. Conclusions: This systematic review is the first to synthesise pharmacy stakeholders' views and experiences of ASPP credentialing. A conceptual framework highlights contextual factors, facilitators, barriers, and inter-relationships which should be considered by pharmacists, policymakers, and other key stakeholders when implementing ASPP credentialing.

Abstract Background Genomic selection has the potential to accelerate genetic gain in perennial ryegrass breeding, provided complex traits such as forage yield can be predicted with sufficient accuracy. Methods In this study, we compared modelling approaches and feature selection strategies to evaluate the accuracy of genomic prediction models for seasonal forage yield production. Results Overall, model selection had limited impact on predictive ability when using the full data set. For a baseline genomic best linear unbiased prediction model, the highest mean predictive accuracy was obtained for spring grazing (0.78), summer grazing (0.62) and second cut silage (0.56). In terms of feature selection strategies, using uncorrelated single‐nucleotide polymorphisms (SNPs) had no impact on predictive ability, allowing for a potential decrease of the data set dimensions. With a genome‐wide association study, we found a significant SNP marker for spring grazing, located in the genic region annotated as coding for an enzyme responsible for fucosylation of xyloglucans—major components of the plant cell wall. We also presented an approach to increase interpretability of genomic prediction models with the use of Gene Ontology enrichment analysis. Conclusions Approaches for feature selection will be relevant in development of low‐cost genotyping platforms in support of routine and cost‐effective implementation of genomic selection.

The safe administration of solid oral dose forms in hospital inpatients with swallowing difficulties is challenging. The aim of this study was to establish the prevalence of difficulties in swallowing solid oral dose forms in acute hospital inpatients. A point prevalence study was completed at three time points. The following data were collected: the prevalence of swallowing difficulties, methods used to modify solid oral dose forms to facilitate administration, the appropriateness of the modification, and patient co-morbidities. The prevalence of acute hospital inpatients with swallowing difficulties was an average of 15.4% with a 95% CI [13.4, 17.6] across the three studies. On average, 9.6% of patients with swallowing difficulties had no enteral feeding tube in situ, with 6.0% of these patients receiving at least one modified medicine. The most common method of solid oral dose form modification was crushing, with an administration error rate of approximately 14.4%. The most common co-morbid condition in these patients was hypertension, with dysphagia appearing on the problem list of two (5.5%) acute hospital inpatients with swallowing difficulties. Inappropriate modifications to solid oral dose forms to facilitate administration can result in patient harm. A proactive approach, such as the use of a screening tool to identify acute hospital inpatients with swallowing difficulties, is required, to mitigate the risk of inappropriate modifications to medicines to overcome swallowing difficulties.

AbstractBackground Pharmacists are increasingly incorporated into general practice teams globally and have been shown to positively impact patient outcomes. However, little research to date has focused on determining general practitioners’ (GPs’) perceptions of practice-based pharmacist roles in countries yet to establish such roles.Objectives To explore GPs’ perceptions towards integrating pharmacists into practices and determine if any significant associations were present between GPs’ perceptions and their demographic characteristics.Methods In June 2022, a survey was disseminated to GPs in Ireland via post (n = 500 in Munster region), Twitter, WhatsApp, and an online GP support and education network. Quantitative data were captured through multiple option and Likert-scale questions and analysed using descriptive and inferential statistics. Qualitative data were captured via free-text boxes, with the open comments analysed using reflexive thematic analysis.Results A total of 152 valid responses were received (24.6% response to postal survey). Overall, GPs welcomed the role of practice-based pharmacists and perceived that they would increase patient safety. Most agreed with practice pharmacists providing medicine information (98%) vs. 23% agreeing with practice pharmacists prescribing independently. Most agreed they would partake in a practice pharmacist pilot (78.6%). The free-text comments described current pressures in general practice, existing relationships with pharmacists, funding and governance strategies, potential roles for pharmacists in general practice, and anticipated outcomes of such roles.Conclusion This study provides a deeper understanding of GPs’ perceptions of integrating pharmacists into practices and the demographic characteristics associated with different perceptions, which may help better inform future initiatives to integrate pharmacists into practices.

Abstract Background Heart failure (HF) guideline-led prescribing improves patient outcomes; however, little is known about the factors influencing guideline-led prescribing in critical care settings. This study used a cross-sectional survey to assess the factors that influence physicians when prescribing to heart failure patients in a critical care setting in Egypt. Results The response rate was 54.8%. The international HF guidelines were the primary source of prescribing information for 84.2% of respondents. Staff were more familiar with the latest guideline recommendations than associate staff (86.7% vs 36.8%, p = 0.012) and considered patient’s perspectives more often (86.7% vs 26.3%, p = 0.036). Renal function was the clinical factor that most frequently influenced the prescribing of loop diuretics or renin–angiotensin–aldosterone system inhibitors. Pulmonary function influenced beta-blockers prescription. The most frequently cited barrier to guideline-led prescribing was the absence of locally drafted guidelines. A majority of prescribers agreed that implementation of clinical pharmacy services, physician education and electronic reminders may improve the implementation of guideline-led prescribing. Conclusions Although experienced physicians are familiar with and use international guidelines, physicians would welcome local guidance on HF prescribing and greater clinical pharmacist input.

The aim of this systematic review was to identify and critically appraise the available evidence regarding solid oral dosage forms (SODFs), e.g., tablets, and challenges regarding the oral administration of medicine to inpatients in a variety of healthcare settings such as (1) hospitals, (2) nursing homes and (3) long-term stay units (LTSUs). A literature search was undertaken in September 2021 and repeated in June 2023 in the following databases: PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, PsycINFO and ProQuest. A Microsoft Excel® spreadsheet was devised to collate the following data from each eligible study: study author and year, country, number of participants, title, duration (follow-up period), study design, inclusion and exclusion criteria, method and data collection, relevant outcomes, and key findings. A total of 3023 records were identified, with 12 articles being included in the final systematic review. Seven of the twelve studies reported on the prevalence of difficulties swallowing SODFs, which varied from 10–34.2%. Nine of the twelve studies reported the methods used to manipulate SODFs, with the most reported method being tablet crushing. Given the prevalence of swallowing difficulties and the subsequent crushing of medicines in response to this, it is evident that concerns should be raised regarding the potential for a medication administration error to occur.

Objectives: We identified factors associated with healthcare costs and health-related quality of life (HRQoL) of multimorbid older adults with polypharmacy. Methods: Using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid older people) trial, we described the magnitude and composition of healthcare costs, and time trends of HRQoL, during 1-year after an acute-care hospitalization. We performed a cluster analysis to identify groups with different cost and HRQoL trends. Using multilevel models, we also identified factors associated with costs and HRQoL. Results: Two months after hospitalization monthly mean costs peaked (CHF 7′124) and HRQoL was highest (0.67). They both decreased thereafter. Age, falls, and comorbidities were associated with higher 1-year costs. Being female and housebound were negatively associated with HRQoL, while moderate alcohol consumption had a positive association. Being independent in daily activities was associated with lower costs and higher HRQoL. Conclusion: Although only some identified potential influences on costs and HRQoL are modifiable, our observations support the importance of prevention before health deterioration in older people with multimorbid illness and associated polypharmacy.

Introduction: Pharmacists in general practice have been shown to enhance patient care and are becoming increasingly prevalent worldwide. Yet, little is known about general practitioners' (GPs') perceptions of pharmacists prior to potentially working alongside them in this setting. Therefore, this study aimed to investigate these GP perceptions to inform future efforts to integrate pharmacists into general practice.Methods: Semi-structured interviews were conducted with GPs practising in the Republic of Ireland between October and December 2021. Content analysis was used to identify the most relevant Theoretical Domains Framework (TDF) domains that affected the theoretical integration of pharmacists into general practice.Results: Fifteen GPs were interviewed. Five TDF domains were found to be most relevant in affecting pharmacist integration: (1) ‘environmental context and resources’ (space, government funding, information technology, current workplace pressures, increasing patient complexity, indemnity, moves towards group practices); (2) ‘skills’ (GP mentors, practical in-service training, consultation skills development); (3) ‘social professional role and identity’ (role definition, clinical governance, pharmacist prescribing, medication review and monitoring); (4) ‘beliefs about consequences’ (patient safety, cost savings, workload); and (5) ‘knowledge’ (pharmacists as medication experts, lack of knowledge of pharmacist undergraduate training).Discussion: This is the first qualitative interview study to focus on exploring GPs' perceptions of pharmacists working in general practice outside of private practice settings. It has provided a deeper understanding of GPs' considerations regarding the integration of pharmacists into general practice. In addition to informing future research, these findings should help optimise future service design and aid pharmacist integration into general practice.

Background: To help address the issue of inappropriate antipsychotic prescribing to nursing home residents with dementia, the ‘Rationalising Antipsychotic Prescribing in Dementia’ (RAPID) complex intervention was developed, comprising staff education and training, academic detailing and a novel resident assessment tool. Objectives: The primary objective was to assess the feasibility and acceptability of the RAPID complex intervention in a nursing home setting. The secondary objective was to describe associated trends in psychotropic prescribing, falls, and behavioural symptoms. Methods: A mixed-methods feasibility intervention study in one large nursing home in Ireland was undertaken between 07/2017 and 01/2018. Focus groups and semi-structured interviews were conducted with nursing home staff and GPs at the end of the 3-month follow up period to assess participants' experience of the intervention. Quantitative measurements included pre- and post-course evaluation and psychotropic prescribing rates. Results: Sixteen nursing home staff members attended the two education and training days (21% attendance rate), and four GPs participated in the academic detailing sessions (100% attendance rate). Participants of the focus groups and interviews (n = 18) found the education and training beneficial for their work and expressed a desire to continue educating new staff after the study's completion. However, there was limited usage of the resident assessment tool. Participants also offered recommendations to enhance the intervention.The proportion of dementia residents prescribed at least one regular antipsychotic was stable over the 3-months pre-intervention at 45% (n = 18), and at baseline at 44% (n = 19) but decreased slightly to 36% (n = 14) at 3-months post-intervention. At the same time the absolute number of ‘PRN’ psychotropics administered monthly to dementia residents decreased substantially from 90 at baseline to 69 at 3-months post-intervention. Conclusion: The RAPID complex intervention was broadly feasible to conduct and may be acceptable to stakeholders. However, before it can be evaluated in larger scale studies, certain protocol modifications and further exploratory work are required to improve implementation.

Abstract Background The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. Methods Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person’s EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. Results 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon’s evenness index score of 0.86) than the EQ-5D-3L (Shannon’s evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. Conclusion Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

Public discourse on medicine provision predominantly focuses on overall expenditure. However, current literature suggests measurement of alternative indicators can provide a method to benchmark or ameliorate medicine provision. Previous research has investigated the viability of using health-related outcome metrics, such as the number of patients treated, quality-adjusted life-year gain and life-year gain, to provide macro-level estimates on medicines’ societal contributions. This editorial provides an overview of the evolving healthcare landscape surrounding medicine usage estimation and valuation in Ireland and offers recommendations on how improved methods of measuring health-related outcomes may help ameliorate efficiencies and the sustainability of a healthcare system.

Abstract Background Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial. Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm. Method This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention. Discussion The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019. Trial registration Universal Trial Number: U1111-1181-9400 Clinicaltrials.gov: NCT02986425 , Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183 . Netherlands Trial Register: NTR6012 (07-10-2016).

BackgroundInappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention.MethodsWe performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics.ResultsTrial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3'588 (95% confidence interval (CI): -7'716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk.ConclusionWe observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries.

We have developed PotatoMASH (Potato Multi-Allele Scanning Haplotags), a novel low-cost, genome-scanning marker platform. We designed a panel of 339 multi-allelic regions placed at 1 Mb intervals throughout the euchromatic portion of the genome. These regions were assayed using a multiplex amplicon sequencing approach, which allows for genotyping hundreds of plants at a cost of 5 EUR/sample. We applied PotatoMASH to a population of over 700 potato lines. We obtained tetraploid dosage calls for 2012 short multi-allelic haplotypes in 334 loci, which ranged from 2 to 14 different haplotypes per locus. The system was able to diagnose the presence of targeted pest-resistance markers, to detect quantitative trait loci (QTLs) by genome-wide association studies (GWAS) in a tetraploid population, and to track variation in a diploid segregating population. PotatoMASH efficiently surveys genetic variation throughout the potato genome, and can be implemented as a single low-cost genotyping platform that will allow the routine and simultaneous application of marker-assisted selection (MAS) and other genotyping applications in commercial potato breeding programmes.

Abstract Background The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients’ current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. Methods We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants’ medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant’s clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial’s primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/− 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy. Trial registration number Clinicaltrials.gov NCT02097654, 27 March 2014.

Background: Antipsychotics are commonly prescribed to people living with dementia in nursing home settings, despite strong guideline recommendations against their use except in limited circumstances. We aimed to transparently describe the development process for a complex intervention targeting appropriate requesting and prescribing of antipsychotics to nursing home residents with dementia in Ireland, by nurses and general practitioners (GPs) respectively. Methods: We report the development process for the ‘Rationalising Antipsychotic Prescribing in Dementia’ (RAPID) complex intervention, in accordance with the ‘Guidance for reporting intervention development studies in health research’ (GUIDED) checklist. The UK Medical Research Council framework for developing and evaluating complex interventions guided our overall approach, incorporating evidence and theory into the intervention development process. To unpack the intervention development process in greater detail, we followed the Behaviour Change Wheel approach. Guided by our stakeholders, we conducted three sequential studies (systematic review and qualitative evidence synthesis, primary qualitative study and expert consensus study), to inform the intervention development. Results: The RAPID complex intervention was developed in collaboration with a broad range of stakeholders, including people living with dementia and family carers, between 2015 and 2017. The finalised RAPID complex intervention was comprised of the following three components; 1) Education and training sessions with nursing home staff; 2) Academic detailing with GPs; 3) Introduction of an assessment tool to the nursing home. Conclusions: This paper describes the steps used by the researchers to develop a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia in Ireland, according to the GUIDED checklist. We found that the GUIDED checklist provided a useful way of reporting all elements in a cohesive manner and complemented the other tools and frameworks used. Transparency in the intervention development processes can help in the translation of evidence into practice.

Background: Developed in the late 20th century, the health policy triangle (HPT) is a policy analysis framework used and applied ubiquitously in the literature to analyse a large number of health-related issues. Objective: To explore and summarise the application of the HPT framework to health-related (public) policy decisions in the recent literature. Methods: This narrative review consisted of a systematic search and summary of included articles from January 2015 January 2020. Six electronic databases were searched. Included studies were required to use the HPT framework as part of their policy analysis. Data were analysed using principles of thematic analysis. Results: Of the 2217 studies which were screened for inclusion, the final review comprised of 54 studies, mostly qualitative in nature. Five descriptive categorised themes emerged (i) health human resources, services and systems, (ii) communicable and non-communicable diseases, (iii) physical and mental health, (iv) antenatal and postnatal care and (v) miscellaneous. Most studies were conducted in lower to upper-middle income countries. Conclusion: This review identified that the types of health policies analysed were almost all positioned at national or international level and primarily concerned public health issues. Given its generalisable nature, future research that applies the HPT framework to smaller scale health policy decisions investigated at local and regional levels, could be beneficial.

Discharge prescriptions for heart failure (HF) patients may not adhere to the clinical practice guidelines. This study aimed to assess the impact of the clinical pharmacist as a member of a multidisciplinary team on the quality of prescribing to HF patients at discharge from a Critical Care Unit (CCU) in Egypt. This was a retrospective cohort study of HF patients discharged from the CCU between January 2013 and December 2017. Guideline Adherence Index (GAI-3) was used to assess guideline-directed prescribing at discharge. Multidisciplinary care was introduced to the CCU on 1 January 2016. The study included 284 HF patients, mean (±SD) age 66.7 ± 11.5 years, 53.2% male. Heart failure with reduced ejection fraction affected 100 patients (35.2%). At discharge, loop diuretics were prescribed to 85.2% of patients; mineralocorticoid receptor antagonists to 54.9%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to 51.4%; and β-blockers to 29.9%. Population Guideline Adherence Index (GAI-3) was 45.5%. High-GAI was prescribed to 136 patients (47.9%). Patients with High-GAI were younger; less affected by chronic kidney disease and had fewer comorbidities than those without High-GAI. Prescription of β-blocker increased (24.1% vs. 38.6%, p < 0.001) and digoxin utilization decreased (34.7% vs. 23.7%, p < 0.049) after the introduction of the multidisciplinary care. The inclusion of a clinical pharmacist in the multidisciplinary care team may have a role in optimizing the prescribing of HF guideline-directed therapies at discharge from this setting.

Potato virus Y (PVY) is the most economically important virus infecting cultivated potato (Solanum tuberosum L.). Accurate diagnosis is crucial to regulate the trade of tubers and for the sanitary selection of plant material for propagation. However, high genetic diversity of PVY represents a challenge for the detection and classification of isolates. Here, the diversity of Irish PVY isolates from a germplasm collection and commercial sites was investigated using conventional molecular and serological techniques. Recombinant PVY isolates were prevalent, with PVYNTNa being the predominant genotype. In addition, we evaluated Nanopore sequencing to detect and reconstruct the whole genome sequence of four viruses (PVY, PVX, PVS, PLRV) and five PVY genotypes in a subset of eight potato plants. De novo assembly of Nanopore sequencing reads produced single contigs covering greater than 90% of the viral genome and sharing greater than 99.5% identity to the consensus sequences obtained with Illumina sequencing. Interestingly, single near full genome contigs were obtained for different isolates of PVY co-infecting the same plant. Mapping reads to available reference viral genomes enabled us to generate near complete genome sequences sharing greater than 99.90% identity to the Illumina-derived consensus. This is the first report describing the use of Oxford Nanopore’s MinION to detect and genotype potato viruses. We reconstructed the genome of PVY and other RNA viruses; indicating the technologies potential for virus detection in potato production systems, and for the study of genetic diversity of highly heterogeneous viruses such as PVY.

Potatoes destined for crisping are normally stored above 8 degrees; below this glucose accumulates leading to very dark fry colors and potential acrylamide build up. Unfortunately, sprouting occurs above 4 degrees and impacts product quality, necessitating the use of sprout suppressant chemicals. Therefore, a goal of breeders is to develop potatoes with excellent fry color, which is maintained under storage below 8 degrees. Genomic or marker-assisted selection offers an opportunity to improve the efficiency of potato breeding and thereby assist breeders in achieving this goal. In this study, we have accumulated fry-color data on a large population of potato lines and combined this with genotypic data to carry out a GWAS and to evaluate accuracy of genomic prediction. We were able to identify a major QTL on chromosome 10 for fry color, and predict fry color with moderate accuracy using genome-wide markers. Furthermore, our results provide evidence that it is possible to identify a small subset of SNPs for processing characteristics that can give moderate predictive ability, albeit lower than that achieved with genome-wide markers.

Background: Severe toxicity is experienced by a substantial minority of patients receiving fluoropyrimidine-based chemotherapy, with approximately 20% of these severe toxicities attributable to polymorphisms in the DPYD gene. The DPYD codes for the enzyme dihydropyrimidine dehydrogenase (DPD) important in the metabolism of fluoropyrimidine-based chemotherapy. We questioned whether prospective DPYD mutation analysis in all patients commencing such therapy would prove more cost-effective than reactive testing of patients experiencing severe toxicity. Methods: All patients experiencing severe toxicity from fluoropyrimidine-based chemotherapy for colorectal cancer in an Irish private hospital over a 3-year period were tested for 4 DPYD polymorphisms previously associated with toxicity. The costs associated with an index admission for toxicity in DPD-deficient patients were examined. A cost analysis was undertaken comparing the anticipated cost of implementing screening for DPYD mutations versus current usual care. One-way sensitivity analysis was conducted on known input variables. An alternative scenario analysis from the perspective of the Irish health-care payer (responsible for public hospitals) was also performed. Results: Of 134 patients commencing first-line fluoropyrimidine chemotherapy over 3 years, 30 (23%) patients developed grade 3/4 toxicity. Of these, 17% revealed heterozygote DPYD mutations. The cost of hospitalization for the DPYD -mutated patients was €232 061, while prospectively testing all 134 patients would have cost €23 718. Prospective testing would result in cost savings across all scenarios. Conclusions: The cost of hospital admission for severe chemotherapy-related toxicity is significantly higher than the cost of prospective DPYD testing of each patient commencing fluoropyrimidine chemotherapy.

Ryegrass single plants, bi-parental family pools, and multi-parental family pools are often genotyped, based on allele-frequencies using genotyping-by-sequencing (GBS) assays. GBS assays can be performed at low-coverage depth to reduce costs. However, reducing the coverage depth leads to a higher proportion of missing data, and leads to a reduction in accuracy when identifying the allele-frequency at each locus. As a consequence of the latter, genomic relationship matrices (GRMs) will be biased. This bias in GRMs affects variance estimates and the accuracy of GBLUP for genomic prediction (GBLUP-GP). We derived equations that describe the bias from low-coverage sequencing as an effect of binomial sampling of sequence reads, and allowed for any ploidy level of the sample considered. This allowed us to combine individual and pool genotypes in one GRM, treating pool-genotypes as a polyploid genotype, equal to the total ploidy-level of the parents of the pool. Using simulated data, we verified the magnitude of the GRM bias at different coverage depths for three different kinds of ryegrass breeding material: individual genotypes from single plants, pool-genotypes from F2 families, and pool-genotypes from synthetic varieties. To better handle missing data, we also tested imputation procedures, which are suited for analyzing allele-frequency genomic data. The relative advantages of the bias-correction and the imputation of missing data were evaluated using real data. We examined a large dataset, including single plants, F2 families, and synthetic varieties genotyped in three GBS assays, each with a different coverage depth, and evaluated them for heading date, crown rust resistance, and seed yield. Cross validations were used to test the accuracy using GBLUP approaches, demonstrating the feasibility of predicting among different breeding material. Bias-corrected GRMs proved to increase predictive accuracies when compared with standard approaches to construct GRMs. Among the imputation methods we tested, the random forest method yielded the highest predictive accuracy. The combinations of these two methods resulted in a meaningful increase of predictive ability (up to 0.09). The possibility of predicting across individuals and pools provides new opportunities for improving ryegrass breeding schemes.

To review pharmacist-led screening programmes for estimation of cardiovascular disease (CVD) risk using validated screening tools, studies were identified using a search of the following electronic databases: PubMed, EMBASE, Web of Knowledge and the Cochrane library databases. Each database was searched from inception to December 2011. The search terms used were: “cardiovascular disease”, “screening”, “risk estimation”, “pharmacist” and “pharmacy”. Titles, abstracts and full manuscripts were screened to determine eligibility. Inclusion criteria were: (i) Pharmacist-led CVD screening; and (ii) Use of validated screening tool or tools for CVD. From each included study information was collected on the following: Study author; year of publication; setting; inclusion and exclusion criteria; tools used and outcomes measured. Articles were grouped and independently verified to ensure they met with the inclusion criteria. Over 7,000 citations were found. Twenty full-length articles were retrieved for analysis, of which twelve were excluded, as they did not meet the inclusion criteria. The eight remaining articles were included in this literature review. Whilst pharmacists undertake screening in their own practice, this approach will only go so far. To have a population-health impact, pharmacists should be involved in proactive screening in a variety of settings.

The implementation of genomic selection (GS) in plant breeding, so far, has been mainly evaluated in crops farmed as homogeneous varieties, and the results have been generally positive. Fewer results are available for species, such as forage grasses, that are grown as heterogenous families (developed from multiparent crosses) in which the control of the genetic variation is far more complex. Here we test the potential for implementing GS in the breeding of perennial ryegrass ( L.) using empirical data from a commercial forage breeding program. Biparental F and multiparental synthetic (SYN) families of diploid perennial ryegrass were genotyped using genotyping-by-sequencing, and phenotypes for five different traits were analyzed. Genotypes were expressed as family allele frequencies, and phenotypes were recorded as family means. Different models for genomic prediction were compared by using practically relevant cross-validation strategies. All traits showed a highly significant level of genetic variance, which could be traced using the genotyping assay. While there was significant genotype × environment (G × E) interaction for some traits, accuracies were high among F families and between biparental F and multiparental SYN families. We have demonstrated that the implementation of GS in grass breeding is now possible and presents an opportunity to make significant gains for various traits.

Objective: To evaluate studies of pharmacist-led interventions on potentially inappropriate prescribing among community-dwelling older adults receiving primary care to identify the components of a successful intervention. Data sources: An electronic search of the literature was conducted using the following databases from inception to December 2015: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE (through Ovid), Trip, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, ISI Web of Science, ScienceDirect, ClinicalTrials.gov , metaRegister of Controlled Trials, ProQuest Dissertations & Theses Database (Theses in Great Britain, Ireland and North America). Review methods: Studies were included if they were randomised controlled trials or quasi-randomised studies involving a pharmacist-led intervention compared to usual/routine care which aimed to reduce potentially inappropriate prescribing in older adults in primary care. Methodological quality of the included studies was independently assessed. Results: A comprehensive literature search was conducted which identified 2193 studies following removal of duplicates. Five studies met the inclusion criteria. Four studies involved a pharmacist conducting a medication review and providing feedback to patients or their family physician. One randomised controlled trial evaluated the effect of a computerised tool that alerted pharmacists when elderly patients were newly prescribed potentially inappropriate medications. Four studies were associated with an improvement in prescribing appropriateness. Conclusion: Overall, this review demonstrates that pharmacist-led interventions may improve prescribing appropriateness in community-dwelling older adults. However, the quality of evidence is low. The role of a pharmacist working as part of a multidisciplinary primary care team requires further investigation to optimise prescribing in this group of patients.

BackgroundPerennial ryegrass is a highly heterozygous outbreeding grass species used for turf and forage production. Heterozygosity can affect de-Bruijn graph assembly making de novo transcriptome assembly of species such as perennial ryegrass challenging. Creating a reference transcriptome from a homozygous perennial ryegrass genotype can circumvent the challenge of heterozygosity. The goals of this study were to perform RNA-sequencing on multiple tissues from a highly inbred genotype to develop a reference transcriptome. This was complemented with RNA-sequencing of a highly heterozygous genotype for SNP calling.ResultDe novo transcriptome assembly of the inbred genotype created 185,833 transcripts with an average length of 830 base pairs. Within the inbred reference transcriptome 78,560 predicted open reading frames were found of which 24,434 were predicted as complete. Functional annotation found 50,890 transcripts with a BLASTp hit from the Swiss-Prot non-redundant database, 58,941 transcripts with a Pfam protein domain and 1,151 transcripts encoding putative secreted peptides. To evaluate the reference transcriptome we targeted the high-affinity K+ transporter gene family and found multiple orthologs. Using the longest unique open reading frames as the reference sequence, 64,242 single nucleotide polymorphisms were found. One thousand sixty one open reading frames from the inbred genotype contained heterozygous sites, confirming the high degree of homozygosity.ConclusionOur study has developed an annotated, comprehensive transcriptome reference for perennial ryegrass that can aid in determining genetic variation, expression analysis, genome annotation, and gene mapping.

Genotyping-by-Sequencing (GBS) is an excellent tool for characterising genetic variation between plant genomes. To date, its use has been reported only for genotyping of single individuals. However, there are many applications where resolving allele frequencies within populations on a genome-wide scale would be very powerful, examples include the breeding of outbreeding species, varietal protection in outbreeding species, monitoring changes in population allele frequencies. This motivated us to test the potential to use GBS to evaluate allele frequencies within populations. Perennial ryegrass is an outbreeding species, and breeding programs are based upon selection on populations. We tested two restriction enzymes for their efficiency in complexity reduction of the perennial ryegrass genome. The resulting profiles have been termed Genome Wide Allele Frequency Fingerprints (GWAFFs), and we have shown how these fingerprints can be used to distinguish between plant populations. Even at current costs and throughput, using sequencing to directly evaluate populations on a genome-wide scale is viable. GWAFFs should find many applications, from varietal development in outbreeding species right through to playing a role in protecting plant breeders' rights.