General practitioners' perceptions of pharmacists working in general practice: a qualitative interview study.

BACKGROUND: Pharmacists are being increasingly employed as part of general practice teams globally, and their input has been associated with several clinical and economic benefits. However, there is a paucity of research focussing on general practitioners' (GPs') perceptions of pharmacist integration into practices in countries where this novel role for pharmacists is yet to become commonplace. OBJECTIVE: To explore GPs' perceptions of integrating pharmacists into general practices and to identify the behavioural determinants of GPs integrating pharmacists into practices. METHODS: Semistructured interviews were conducted with GPs practising in Ireland, who were sampled using a combination of purposive, convenience, and snowball sampling. Interviews were audio-recorded and transcribed verbatim, which then were analysed using conventional content analysis and directed content analysis employing the Theoretical Domains Framework (TDF). RESULTS: Seventeen GPs were interviewed between November 2021 and February 2022. Seven TDF domains were identified as predominant in influencing GPs' perceptions of pharmacist integration into general practices. These perceptions were mostly positive, especially regarding patient outcomes, cost savings, and improving access to care. However, there were concerns about funding the role, affecting others' workloads, and pharmacists' training needs to work in practices. CONCLUSION: This study's theory-informed insight provides a deeper understanding of GPs' perceptions of pharmacists working in general practice and behaviours which can be targeted to help optimize integration. These findings should be utilized in future service development to preempt and address GPs' concerns ahead of pharmacist integration, as well as to inform the development of general practice-based pharmacist roles going forward.

This interview study focusses on, for the first time, general practitioners' (GPs') perceptions of pharmacist integration into general practices outside of a private practice setting. Pharmacists working in general practices have demonstrated several benefits for patients, GPs, practices, and for wider society. However, pharmacist roles in general practices have thus far been confined to a small number of countries; little is known about the perceptions of GPs who have not previously worked alongside a pharmacist in general practice regarding pharmacist integration in this setting. GPs interviewed in this study were broadly optimistic about aspects of pharmacists working in practices and potential outputs. However, GPs had concerns about pharmacists' impact on others' roles and workloads, funding, and training pharmacists to perform roles in this setting. This study therefore provides a useful insight into GPs' perceptions on the subject so that their views, concerns, and ideas can be anticipated and taken on board in advance of trying to integrate pharmacists into practices.

General practitioners' perceptions of pharmacists working in general practice: a qualitative interview study.

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.

Electrochemical Modification of Polypeptides at Selenocysteine.

Mild strategies for the selective modification of peptides and proteins are in demand for applications in therapeutic peptide and protein discovery, and in the study of fundamental biomolecular processes. Herein, we describe the development of an electrochemical selenoetherification (e-SE) platform for the efficient site-selective functionalization of polypeptides. This methodology utilizes the unique reactivity of the 21st amino acid, selenocysteine, to effect formation of valuable bioconjugates through stable selenoether linkages under mild electrochemical conditions. The power of e-SE is highlighted through late-stage C-terminal modification of the FDA-approved cancer drug leuprolide and assembly of a library of anti-HER2 affibody conjugates bearing complex cargoes. Following assembly by e-SE, the utility of functionalized affibodies for in vitro imaging and targeting of HER2 positive breast and lung cancer cell lines is also demonstrated.

Factors affecting physician implementation of hospital pharmacists' medication appropriateness recommendations in older adults.

AIMS: Non-implementation of pharmacist recommendations by physician prescribers may prolong potentially inappropriate prescribing in hospitalised older adults, increasing the risk of adverse clinical outcomes. The aim of this study was to ascertain the key factors affecting physician prescriber implementation of pharmacists' medication appropriateness recommendations in hospitalised older adults. METHODS: Semi-structured interviews were conducted with hospital pharmacists and physicians who provided care to older adults (≥65 years) in 2 acute university teaching hospitals in Ireland. Content analysis was employed to identify the key themes that influence physician prescriber implementation of pharmacist recommendations. RESULTS: Fourteen interviews were conducted with 6 hospital pharmacists and 8 hospital physicians between August 2018 and August 2019. Five key factors were found to affect physician implementation of pharmacist recommendations: (i) the clinical relevance and complexity of the recommendation-recommendations of higher priority and those that do not require complex decision-making are implemented more readily; (ii) interprofessional communication-recommendations provided verbally, particularly those communicated face to face with confidence and assertion, are more likely to be implemented than written recommendations; (iii) physician role and identity-the grade, specialty, and personality of the physician significantly affect implementation; (iv) knowing each other and developing trusting relationships-personal acquaintance and the development of interprofessional trust and rapport greatly facilitate recommendation implementation; and (v) the hospital environment-organisational issues such as documentation in the patient notes, having the opportunity to intervene, and the clinical pharmacy model all affect implementation. CONCLUSION: This study provides a deeper understanding of the underlying behavioural determinants affecting physician prescriber implementation of pharmacist recommendations and will aid in the development of theoretically-informed interventions to improve medication appropriateness in hospitalised older adults.

General practitioners' views of pharmacist services in general practice: a qualitative evidence synthesis.

BACKGROUND: Pharmacist services in general practice are expanding worldwide, with evidence to show pharmacists' presence in general practice has financial, workload, and clinical benefits. Yet, little is known globally about general practitioners' (GPs') views on their presence in general practice. OBJECTIVE: To synthesize the qualitative research evidence on GPs' views of pharmacist services in general practice. METHODS: Qualitative evidence synthesis; 8 electronic databases were searched from inception to April 2021 for qualitative studies that reported the views of GPs regarding pharmacist services in general practice. Data from included studies were analyzed using thematic synthesis. The Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach was used to assess the confidence in individual review findings. RESULTS: Nineteen studies were included, which captured the views of 159 GPs from 8 different countries. Four analytical themes describing the factors that should be considered in the development or optimization of pharmacist services in general practice, based on the views of GPs, were developed from the coded data and descriptive themes: (i) optimal environment for a pharmacist, (ii) the ideal pharmacist characteristics, (iii) complex stakeholder relationships, and (iv) benefits of an effective pharmacist. CONCLUSION: Based on the synthesis of GPs' views, we have created a conceptual model of factors that should be considered by policymakers, GPs, pharmacists, and other relevant stakeholders when developing or optimizing pharmacist services in general practice going forward.

This review presents the evidence, for the first time, on general practitioners' (GPs') views of pharmacist services in the general practice setting worldwide. Pharmacist services in general practice have the potential to yield several benefits for the practice, patient, and GPs themselves. However, to include pharmacist services in the practice is a complex process; this review gives an insight into GPs' thoughts on the matter, what works­and if so, why­and what does not work. This review will therefore prove useful to GPs, pharmacists, practice managers, policymakers, and academics wishing to establish or improve pharmacist services in the general practice environment.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 µg daily, or 25 µg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 µg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).

Measurement properties of EQ-5D-3L and EQ-5D-5L in recording self-reported health status in older patients with substantial multimorbidity and polypharmacy.

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.

Computer-generated STOPP/START recommendations for hospitalised older adults: evaluation of the relationship between clinical relevance and rate of implementation in the SENATOR trial.

BACKGROUND: findings from a recent qualitative study indicate that the perceived clinical relevance of computer-generated STOPP/START recommendations was a key factor affecting their implementation by physician prescribers caring for hospitalised older adults in the SENATOR trial. AIM: to systematically evaluate the clinical relevance of these recommendations and to establish if clinical relevance significantly affected the implementation rate. METHODS: a pharmacist-physician pair retrospectively reviewed the case records for all SENATOR trial intervention patients at Cork University Hospital and assigned a degree of clinical relevance for each STOPP/START recommendation based on a previously validated six-point scale. The chi-square test was used to quantify the differences in prescriber implementation rates between recommendations of varying clinical relevance, with statistical significance set at P < 0.05. RESULTS: in 204 intervention patients, the SENATOR software produced 925 STOPP/START recommendations. Nearly three quarters of recommendations were judged to be clinically relevant (73.6%); however, nearly half of these were deemed of 'possibly low relevance' (320/681; 47%). Recommendations deemed of higher clinical relevance were significantly more likely to be implemented than those of lower clinical relevance (P < 0.05). CONCLUSIONS: a large proportion (61%) of the computer-generated STOPP/START recommendations provided were of potential 'adverse significance', of 'no clinical relevance' or of 'possibly low relevance'. The adjudicated clinical relevance of computer-generated medication recommendations significantly affects their implementation. Meticulous software refinement is required for future interventions of this type to increase the proportion of recommendations that are of high clinical relevance. This should facilitate their implementation, resulting in prescribing optimisation and improved clinical outcomes for multimorbid older adults.

Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

Intervention protocol: OPtimising thERapy to prevent avoidable hospital Admission in the Multi-morbid elderly (OPERAM): a structured medication review with support of a computerised decision support system.

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).

Pooled DNA sequencing to identify SNPs associated with a major QTL for bacterial wilt resistance in Italian ryegrass (Lolium multiflorum Lam.).

KEY MESSAGE: SNPs and candidate genes associated with bacterial wilt resistance in Italian ryegrass were identified by sequencing the parental plants and pooled F1 progeny of a segregating population. Italian ryegrass (Lolium multiflorum Lam.) is one of the most important forage grass species in temperate regions. Its yield, quality and persistency can significantly be reduced by bacterial wilt, a serious disease caused by Xanthomonas translucens pv. graminis. Although a major QTL for bacterial wilt resistance has previously been reported, detailed knowledge on underlying genes and DNA markers to allow for efficient resistance breeding strategies is currently not available. We used pooled DNA sequencing to characterize a major QTL for bacterial wilt resistance of Italian ryegrass and to develop inexpensive sequence-based markers to efficiently target resistance alleles for marker-assisted recurrent selection. From the mapping population segregating for the QTL, DNA of 44 of the most resistant and 44 of the most susceptible F1 individuals was pooled and sequenced using the Illumina HiSeq 2000 platform. Allele frequencies of 18 × 106 single nucleotide polymorphisms (SNP) were determined in the resistant and susceptible pool. A total of 271 SNPs on 140 scaffold sequences of the reference parental genome showed significantly different allele frequencies in both pools. We converted 44 selected SNPs to KASP™ markers, genetically mapped these proximal to the major QTL and thus validated their association with bacterial wilt resistance. This study highlights the power of pooled DNA sequencing to efficiently target binary traits in biparental mapping populations. It delivers genome sequence data, SNP markers and potential candidate genes which will allow to implement marker-assisted strategies to fix bacterial wilt resistance in outcrossing breeding populations of Italian ryegrass.

Qualitative analysis of community pharmacists' opinions on their involvement in reducing potentially inappropriate prescribing.

PURPOSE: Older people are at risk of potentially inappropriate prescribing (PIP) due to polypharmacy arising from multi-morbidity. Despite available explicit criteria to reduce PIP, it is highly prevalent. Whilst community pharmacists have the required knowledge to help reduce PIP, they are not currently engaged with the problem. This study explores the views of community pharmacists on their potential involvement in reducing PIP and determines the challenges to its implementation. METHODS: Semi-structured interviews with pharmacists working in community pharmacies in Ireland. The theoretical domains framework (TDF) was used to develop the topic guide and to analyse the transcripts. Domains of highest relevance for PIP reduction were identified based on their frequency or whether the participants emphasised the impact of constructs within a domain. Local ethical approval was obtained. RESULTS: Of 18 participants, 12 were female, median age was 30 years (IQR, 27-35) with a median of 6 years (IQR, 3-8) of experience. Seven TDF domains were identified as relevant to PIP reduction. Pharmacists were uncertain about their role in reducing PIP and reluctant to challenge physicians' prescribing decisions. Challenges pertained to the environment, knowledge, social influences, professional role and identity. CONCLUSIONS: Pharmacists welcomed new responsibilities in reducing PIP as part of their daily practice but expressed a need for removal of social and environmental barriers as well as, provision of relevant guidelines and education about PIP. This study provides useful insights into the target domains for overcoming barriers of pharmacist involvement in reducing PIP.

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol.

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.

Genomic prediction of crown rust resistance in Lolium perenne.

BACKGROUND: Genomic selection (GS) can accelerate genetic gains in breeding programmes by reducing the time it takes to complete a cycle of selection. Puccinia coronata f. sp lolli (crown rust) is one of the most widespread diseases of perennial ryegrass and can lead to reductions in yield, persistency and nutritional value. Here, we used a large perennial ryegrass population to assess the accuracy of using genome wide markers to predict crown rust resistance and to investigate the factors affecting predictive ability. RESULTS: Using these data, predictive ability for crown rust resistance in the complete population reached a maximum of 0.52. Much of the predictive ability resulted from the ability of markers to capture genetic relationships among families within the training set, and reducing the marker density had little impact on predictive ability. Using permutation based variable importance measure and genome wide association studies (GWAS) to identify and rank markers enabled the identification of a small subset of SNPs that could achieve predictive abilities close to those achieved using the complete marker set. CONCLUSION: Using a GWAS to identify and rank markers enabled a small panel of markers to be identified that could achieve higher predictive ability than the same number of randomly selected markers, and predictive abilities close to those achieved with the entire marker set. This was particularly evident in a sub-population characterised by having on-average higher genome-wide linkage disequilibirum (LD). Higher predictive abilities with selected markers over random markers suggests they are in LD with QTL. Accuracy due to genetic relationships will decay rapidly over generations whereas accuracy due to LD will persist, which is advantageous for practical breeding applications.

Identification of behaviour change techniques in deprescribing interventions: a systematic review and meta-analysis.

AIMS: Deprescribing interventions safely and effectively optimize medication use in older people. However, questions remain about which components of interventions are key to effectively reduce inappropriate medication use. This systematic review examines the behaviour change techniques (BCTs) of deprescribing interventions and summarizes intervention effectiveness on medication use and inappropriate prescribing. METHODS: MEDLINE, EMBASE, Web of Science and Academic Search Complete and grey literature were searched for relevant literature. Randomized controlled trials (RCTs) were included if they reported on interventions in people aged ≥65 years. The BCT taxonomy was used to identify BCTs frequently observed in deprescribing interventions. Effectiveness of interventions on inappropriate medication use was summarized in meta-analyses. Medication appropriateness was assessed in accordance with STOPP criteria, Beers' criteria and national or local guidelines. Between-study heterogeneity was evaluated by I-squared and Chi-squared statistics. Risk of bias was assessed using the Cochrane Collaboration Tool for randomized controlled studies. RESULTS: Of the 1561 records identified, 25 studies were included in the review. Deprescribing interventions were effective in reducing number of drugs and inappropriate prescribing, but a large heterogeneity in effects was observed. BCT clusters including goals and planning; social support; shaping knowledge; natural consequences; comparison of behaviour; comparison of outcomes; regulation; antecedents; and identity had a positive effect on the effectiveness of interventions. CONCLUSIONS: In general, deprescribing interventions effectively reduce medication use and inappropriate prescribing in older people. Successful deprescribing is facilitated by the combination of BCTs involving a range of intervention components.

Longitudinal patterns of potentially inappropriate prescribing in early old-aged people.

PURPOSE: It is contentious whether potentially inappropriate prescribing (PIP) is predominantly a phenomenon of late life or whether it has its origins in early old age. This study examined the pattern of PIP in an early old-aged population over 5 years. METHODS: Secondary data analysis of a population-based primary care cohort, of patients aged 60-74 years. Medication data were extracted from electronic patient records in addition to information on comorbidities and demographics. Explicit START criteria (PPOs) and STOPP criteria (PIMs) were used to identify PIP. Generalised estimating equations were used to describe trends in PIP over time and adjusted for age, gender and number of medicines. RESULTS: A total of 978 participants (47.8%) aged 60-74 years were included from the cohort. At baseline, PPOs were detected in 31.2% of patients and PIMs were identified in 35.6% at baseline. Prevalence of PPOs and PIMs increased significantly over time (OR 1.08, 95% CI 1.07; 1.09 and OR 1.04, 95% CI 1.0; 1.06, respectively). A higher number of medicines and new diagnoses were associated with the increasing trend in both PPO and PIM prevalence observed over time, independent of PPOs and PIMs triggered by drug combinations. CONCLUSIONS: Potentially inappropriate prescribing is highly prevalent among early old-aged people in primary care and increases as they progress to more advanced old age, suggesting that routine application of STOPP/START criteria in this population would significantly improve medication appropriateness.

A tool for assessment of heart failure prescribing quality: A systematic review and meta-analysis.

INTRODUCTION: Heart failure (HF) guidelines aim to standardise patient care. Internationally, prescribing practice in HF may deviate from guidelines and so a standardised tool is required to assess prescribing quality. A systematic review and meta-analysis were performed to identify a quantitative tool for measuring adherence to HF guidelines and its clinical implications. METHODS: Eleven electronic databases were searched to include studies reporting a comprehensive tool for measuring adherence to prescribing guidelines in HF patients aged ≥18 years. Qualitative studies or studies measuring prescription rates alone were excluded. Study quality was assessed using the Good ReseArch for Comparative Effectiveness Checklist. RESULTS: In total, 2455 studies were identified. Sixteen eligible full-text articles were included (n = 14 354 patients, mean age 69 ± 8 y). The Guideline Adherence Index (GAI), and its modified versions, was the most frequently cited tool (n = 13). Other tools identified were the Individualised Reconciled Evidence Recommendations, the Composite Heart Failure Performance, and the Heart Failure Scale. The meta-analysis included the GAI studies of good to high quality. The average GAI-3 was 62%. Compared to low GAI, high GAI patients had lower mortality rate (7.6% vs 33.9%) and lower rehospitalisation rates (23.5% vs 24.5%); both P ≤ .05. High GAI was associated with reduced risk of mortality (hazard ratio = 0.29, 95% confidence interval, 0.06-0.51) and rehospitalisation (hazard ratio = 0.64, 95% confidence interval, 0.41-1.00). No tool was used to improve prescribing quality. CONCLUSION: The GAI is the most frequently used tool to assess guideline adherence in HF. High GAI is associated with improved HF outcomes.

Computerised interventions designed to reduce potentially inappropriate prescribing in hospitalised older adults: a systematic review and meta-analysis.

Background: computerised interventions have been suggested as an effective strategy to reduce potentially inappropriate prescribing (PIP) for hospitalised older adults. This systematic review and meta-analysis examined the evidence for efficacy of computerised interventions designed to reduce PIP in this patient group. Methods: an electronic literature search was conducted using eight databases up to October 2017. Included studies were controlled trials of computerised interventions aiming to reduce PIP in hospitalised older adults (≥65 years). Risk of bias was assessed using Cochrane's Effective Practice and Organisation of Care criteria. Results: of 653 records identified, eight studies were included-two randomised controlled trials, two interrupted time series analysis studies and four controlled before-after studies. Included studies were mostly at a low risk of bias. Overall, seven studies showed either a statistically significant reduction in the proportion of patients prescribed a potentially inappropriate medicine (PIM) (absolute risk reduction {ARR} 1.3-30.1%), or in PIMs ordered (ARR 2-5.9%). However, there is insufficient evidence thus far to suggest that these interventions can routinely improve patient-related outcomes. It was only possible to include three studies in the meta-analysis-which demonstrated that intervention patients were less likely to be prescribed a PIM (odds ratio 0.6; 95% CI 0.38, 0.93). No computerised intervention targeting potential prescribing omissions (PPOs) was identified. Conclusions: this systematic review concludes that computerised interventions are capable of statistically significantly reducing PIMs in hospitalised older adults. Future interventions should strive to target both PIMs and PPOs, ideally demonstrating both cost-effectiveness data and clinically significant improvements in patient-related outcomes.

A Gene Encoding a DUF247 Domain Protein Cosegregates with the S Self-Incompatibility Locus in Perennial Ryegrass.

The grass family (Poaceae), the fourth largest family of flowering plants, encompasses the most economically important cereal, forage, and energy crops, and exhibits a unique gametophytic self-incompatibility (SI) mechanism that is controlled by at least two multiallelic and independent loci, S and Z. Despite intense research efforts over the last six decades, the genes underlying S and Z remain uncharacterized. Here, we report a fine-mapping approach to identify the male component of the S-locus in perennial ryegrass (Lolium perenne L.) and provide multiple evidence that a domain of unknown function 247 (DUF247) gene is involved in its determination. Using a total of 10,177 individuals from seven different mapping populations segregating for S, we narrowed the S-locus to a genomic region containing eight genes, the closest recombinant marker mapping at a distance of 0.016 cM. Of the eight genes cosegregating with the S-locus, a highly polymorphic gene encoding for a protein containing a DUF247 was fully predictive of known S-locus genotypes at the amino acid level in the seven mapping populations. Strikingly, this gene showed a frameshift mutation in self-compatible darnel (Lolium temulentum L.), whereas all of the self-incompatible species of the Festuca-Lolium complex were predicted to encode functional proteins. Our results represent a major step forward toward understanding the gametophytic SI system in one of the most important plant families and will enable the identification of additional components interacting with the S-locus.

Genomic prediction of starch content and chipping quality in tetraploid potato using genotyping-by-sequencing.

KEY MESSAGE: Genomic prediction models for starch content and chipping quality show promising results, suggesting that genomic selection is a feasible breeding strategy in tetraploid potato. Genomic selection uses genome-wide molecular markers to predict performance of individuals and allows selections in the absence of direct phenotyping. It is regarded as a useful tool to accelerate genetic gain in breeding programs, and is becoming increasingly viable for crops as genotyping costs continue to fall. In this study, we have generated genomic prediction models for starch content and chipping quality in tetraploid potato to facilitate varietal development. Chipping quality was evaluated as the colour of a potato chip after frying following cold induced sweetening. We used genotyping-by-sequencing to genotype 762 offspring, derived from a population generated from biparental crosses of 18 tetraploid parents. Additionally, 74 breeding clones were genotyped, representing a test panel for model validation. We generated genomic prediction models from 171,859 single-nucleotide polymorphisms to calculate genomic estimated breeding values. Cross-validated prediction correlations of 0.56 and 0.73 were obtained within the training population for starch content and chipping quality, respectively, while correlations were lower when predicting performance in the test panel, at 0.30-0.31 and 0.42-0.43, respectively. Predictions in the test panel were slightly improved when including representatives from the test panel in the training population but worsened when preceded by marker selection. Our results suggest that genomic prediction is feasible, however, the extremely high allelic diversity of tetraploid potato necessitates large training populations to efficiently capture the genetic diversity of elite potato germplasm and enable accurate prediction across the entire spectrum of elite potatoes. Nonetheless, our results demonstrate that GS is a promising breeding strategy for tetraploid potato.