Cost avoidance of pharmacist-led deprescribing using STOPPFrail for older adults in nursing homes.

BACKGROUND: The Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy (STOPPFrail) criteria aim to reduce inappropriate/unnecessary medications in frail older adults, which should minimise adverse drug events and additional healthcare expenditure. Little is known about the economic outcomes of applying these criteria as an intervention. AIM: To evaluate cost avoidance of pharmacist-led application of STOPPFrail to frail older nursing home residents with limited life expectancy. METHOD: Pharmacist-identified STOPPFrail-defined potentially inappropriate medications that were deprescribed by patients' general practitioners were assigned a rating by a multidisciplinary panel, i.e. the probability of an adverse drug event occurring if the medication was not deprescribed. The intervention's net cost benefit and cost-benefit ratio were then determined by factoring in adverse drug event cost avoidance (calculated from probability of adverse drug event ratings), direct cost savings (deprescribed medication costs/reimbursement fees), and healthcare professionals' salaries. RESULTS: Of the 176 potentially inappropriate medications deprescribed across 69 patients, 65 (36.9%) were rated as having a medium or high probability of an adverse drug event occurring if not deprescribed. With €27,162 for direct cost savings, €61,336 for adverse drug event cost avoidance, and €2,589 for healthcare professionals' salary costs, there was a net cost benefit of €85,909 overall. The cost-benefit ratio was 33.2 and remained positive in all scenarios in sensitivity analyses. CONCLUSION: Pharmacist-led application of STOPPFrail to frail older nursing home residents is associated with significant cost avoidance. Wider implementation of pharmacist interventions in frail older nursing home residents should be considered to reduce potentially inappropriate medications and patient harm, alongside substantial cost savings for healthcare systems.

Pharmacist-Led Deprescribing Using STOPPFrail for Frail Older Adults in Nursing Homes.

OBJECTIVES: To evaluate the impact of pharmacist-guided deprescribing using the STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with a limited life expectancy) criteria in frail older nursing home residents. DESIGN: Prospective, unblinded, nonrandomized, intervention study. SETTING AND PARTICIPANTS: Adults ≥65 years with advanced frailty resident in 6 independent nursing homes in Ireland. METHODS: STOPPFrail-based deprescribing recommendations were developed by a pharmacist and presented to residents' general practitioners (GPs), who decided to implement or not. Measured outcomes included number of prescribed medications, medication costs, anticholinergic cognitive burden (ACB), drug burden index (DBI), modified medication appropriateness index (MMAI), quality of life (QoL), nonelective hospitalizations, emergency department visits, falls, and mortality were measured at baseline, post review, and at 6 months post review. RESULTS: Ninety-nine residents were recruited. Most (94%) were prescribed ≥1 potentially inappropriate medication (PIM). The most frequent PIMs were medications without a clearly documented indication (29.6%) and vitamin D (16.9%). Of 348 recommendations provided to GPs, 203 (58%) were accepted and 193 (55%) were implemented. Relating to baseline, post review, and at 6 months: the mean ± standard deviation (SD) number of medications was 16.0 ± 6.1, 14.6 ± 5.7 (P < .001), and 15.4 ± 5.5 (P < .001). The monthly mean ± SD medication cost per patient was €186.8 ± 123.7, €172.7 ± 119.0 (P < .001), and €186.4 ± 121.2 (P = .95). There were significant post-review decreases in the mean DBI, ACB, and MMAI of 9.7%, 9.6%, and 3.7%, respectively (P < .001), which remained significant at 6 months (P < .001). There were no significant differences in falls, emergency department visits, nonelective hospitalizations, or QoL. CONCLUSIONS AND IMPLICATIONS: STOPPFrail-guided deprescribing led by a pharmacist in nursing homes appeared to significantly reduce PIMs, medication costs (initially), and anticholinergic and sedative burdens, without adversely affecting other patient outcomes. Greater consideration should therefore be given to the wider integration of pharmacists into nursing homes to optimize the medications and health outcomes of frail older adults.

Sex differences in patterns of potentially inappropriate prescribing and adverse drug reactions in hospitalized older people: Findings from the SENATOR trial.

BACKGROUND: Older women experience more adverse drug reactions (ADRs) than older men. However, the underlying basis for this sex difference is unclear. Sex (biological status) and/or gender (sociocultural constructs) influences on patterns of inappropriate prescribing in multimorbid older adults may be one reason for this ADR sex difference. In this secondary analysis, we examined whether incident ADR sex differences could be related to concurrent sex differences in potentially inappropriate prescribing. DESIGN AND SETTING: A retrospective secondary analysis of sex differences in the prevalence of potentially inappropriate medications (PIMs), potential prescribing omissions (PPOs), and ADRs among the 1537 participants (47.2% female, median [IQR] age 78 [72-84] years) was undertaken in the SENATOR clinical trial database, conducted in six large European medical centers. PARTICIPANTS AND METHODS: We looked specifically for male/female differences relating to PIMs and PPOs (defined by STOPP/START version 2 criteria) identified within 48 h of acute hospitalization. We also assessed sex differences for ADRs identified at 14 days from admission or discharge, whichever came first. ADRs were assessed by blinded endpoint adjudication panel consensus. RESULTS: During hospitalization, significantly more females experienced ≥1 ADR compared to males (28% and 21%, respectively; odds ratio 1.40, 95% CI 1.10-1.78, p < 0.005). Nine of the 11 STOPP-criteria PIMs showing a significant sex difference occurred more often in females. Of the four START-criteria PPOs showing a significant sex difference, all occurred more often in females. Some sex-associated PIMs reflect higher prevalence of related conditions in older women. CONCLUSION: We conclude that specific STOPP-criteria PIMs and START-criteria PPOs were identified more frequently in older women than older men during acute hospitalization, possibly contributing to higher ADR incidence in older women. Prescribers should appreciate sex differences in exposure to potentially inappropriate prescribing and ADR risk, given the preponderance of older women over older men in most clinical settings.

Point Prevalence Survey of Acute Hospital Patients with Difficulty Swallowing Solid Oral Dose Forms.

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.

Economic cost-benefit analysis of person-centred medicines reviews by general practice pharmacists.

BACKGROUND: Medicines reviews by general practice pharmacists improve patient outcomes, but little is known about the associated economic outcomes, particularly in patients at higher risk of medicines-related harm. AIM: To conduct an economic cost-benefit analysis of pharmacists providing person-centred medicines reviews to patients with hyperpolypharmacy (prescribed ≥ 10 regular medicines) and/or at high risk of medicines-related harm across multiple general practice settings. METHOD: Service delivery costs were calculated based on the pharmacist's salary, recorded timings, and a general practitioner fee. Direct cost savings were calculated from the cost change of patients' medicines post review, projected over 1 year. Indirect savings were calculated using two models, a population-based model for avoidance of hospital admissions due to adverse drug reactions and an intervention-based model applying a probability of adverse drug reaction avoidance. Sensitivity analyses were performed using varying workday scenarios. RESULTS: Based on 1471 patients (88.4% with hyperpolypharmacy), the cost of service delivery was €153 per review. Using the population-based model, net cost savings ranging from €198 to €288 per patient review and from €73,317 to €177,696 per annum per pharmacist were calculated. Using the intervention-based model, net cost savings of €651-€741 per review, with corresponding annual savings of €240,870-€457,197 per annum per pharmacist, were calculated. Savings ratios ranged from 181 to 584% across all models and inputs. CONCLUSION: Person-centred medicines reviews by general practice pharmacists for patients at high risk of medicines-related harm result in substantial cost savings. Wider investment in general practice pharmacists will be beneficial to minimise both patient harm and healthcare system expenditure.

Mefentrifluconazole sensitivity amongst European Zymoseptoria tritici populations and potential implications for its field efficacy.

BACKGROUND: Septoria tritici blotch caused by Zymoseptoria tritici continues to be one of the most economically destructive diseases of winter wheat in north-western Europe. Control is heavily reliant on the application of fungicides, in particular those belonging to the azole group. Here we describe the sensitivity of European Z. tritici populations to the novel azole mefentrifluconazole and the analysis of associated mechanisms of resistance. RESULTS: A wide range of sensitivity to mefentrifluconazole was observed amongst the Z. tritici collections examined, with strong cross-resistances also observed between mefentrifluconazole, difenoconazole and tebuconazole. Overall, the Irish population displayed the lowest sensitivity to all azoles tested. Further detailed analysis of the Irish population in 2021 demonstrated differences in sensitivity occurred between sampling sites, with these differences associated with the frequencies of key resistance mechanisms (CYP51 alterations and MFS1 promoter inserts linked to overexpression). Under glasshouse conditions reductions in the efficacy of mefentrifluconazole were observed towards those strains exhibiting the lowest in vitro sensitivities. CONCLUSIONS: This study demonstrates that a large range of sensitivity to mefentrifluconazole exists in European Z. tritici populations. Those strains exhibiting the lowest sensitivity to the azoles tested had the most complex CYP51 haplotypes in combination with the 519 bp insert, associated with enhanced activity of MFS1. The future use of mefentrifluconazole should take these findings into consideration to minimise the selection of these strains. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Diabetes mellitus increases risk of adverse drug reactions and death in hospitalised older people: the SENATOR trial.

PURPOSE: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, especially in older people. Older people with diabetes mellitus may be at especially high risk of ADRs but this risk has not been well studied. This study aimed to compare severity and type of ADRs in hospitalised, multimorbid older people with and without diabetes and secondly to assess the impact of ADRs on mortality, rehospitalisation and length of stay. METHODS: Participants in the SENATOR (Software Engine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons) trial were assessed for 12 common and 'other' prevalent and incident adverse drug reactions using a blinded end-point adjudication process. Descriptive analyses, logistic regression and mediation analyses were undertaken. RESULTS: Of 1537 people in the SENATOR trial, 540 (35.1%) had diabetes mellitus (mean age 77.4 ± 7.3 years, 58.5% male). In the total population, 773 prevalent and 828 incident ADRs were reported. Both prevalent and incident symptomatic hypoglycaemia and incident acute kidney injury (AKI) were significantly more common in people with diabetes (p < 0.05). Patients with diabetes had higher all-cause mortality at 12 weeks than those without (9.1% vs 6.3%, p = 0.04). Mediation analysis revealed that mortality was significantly higher (OR = 1.43, Sobel test p = 0.048) in people with diabetes and ADRs causing AKI. CONCLUSIONS: Older multimorbid people with diabetes presenting to hospital with acute illness have significantly more ADRs than those without, and a significantly higher mortality that is mediated by medication-associated AKI and poorer renal function.

GPs' perceptions of pharmacists working in general practices: A mixed methods survey study.

BACKGROUND: 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.

Adult Patients with Difficulty Swallowing Oral Dosage Forms: A Systematic Review of the Quantitative Literature.

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.

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.

Overtreatment and associated risk factors among multimorbid older patients with diabetes.

BACKGROUND: In multimorbid older patients with type 2 diabetes mellitus (T2DM), the intensity of glucose-lowering medication (GLM) should be focused on attaining a suitable level of glycated hemoglobin (HbA1c ) while avoiding side effects. We aimed at identifying patients with overtreatment of T2DM as well as associated risk factors. METHODS: In a secondary analysis of a multicenter study of multimorbid older patients, we evaluated HbA1c levels among patients with T2DM. Patients were aged ≥70 years, with multimorbidity (≥3 chronic diagnoses) and polypharmacy (≥5 chronic medications), enrolled in four university medical centers across Europe (Belgium, Ireland, Netherlands, and Switzerland). We defined overtreatment as HbA1c < 7.5% with ≥1 GLM other than metformin, as suggested by Choosing Wisely and used prevalence ratios (PRs) to evaluate risk factors of overtreatment in age- and sex-adjusted analyses. RESULTS: Among the 564 patients with T2DM (median age 78 years, 39% women), mean ± standard deviation HbA1c was 7.2 ± 1.2%. Metformin (prevalence 51%) was the most frequently prescribed GLM and 199 (35%) patients were overtreated. The presence of severe renal impairment (PR 1.36, 1.21-1.53) and outpatient physician (other than general practitioner [GP], i.e. specialist) or emergency department visits (PR 1.22, 1.03-1.46 for 1-2 visits, and PR 1.35, 1.19-1.54 for ≥3 visits versus no visits) were associated with overtreatment. These factors remained associated with overtreatment in multivariable analyses. CONCLUSIONS: In this multicountry study of multimorbid older patients with T2DM, more than one third were overtreated, highlighting the high prevalence of this problem. Careful balancing of benefits and risks in the choice of GLM may improve patient care, especially in the context of comorbidities such as severe renal impairment, and frequent non-GP healthcare contacts.

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.

Healthcare Costs and Health-Related Quality of Life in Older Multimorbid Patients After Hospitalization.

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.

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.

Rationalising Antipsychotic Prescribing in Dementia (RAPID) complex intervention: A mixed-methods feasibility intervention study.

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.

ThinkCascades: A Tool for Identifying Clinically Important Prescribing Cascades Affecting Older People.

BACKGROUND AND OBJECTIVE: Prescribing cascades occur when a drug is prescribed to manage side effects of another drug, typically when a side effect is misinterpreted as a new condition. A consensus list of clinically important prescribing cascades that adversely affect older persons' health (i.e., where risks of the prescribing cascade usually exceed benefits) was developed to help identify, prevent, and manage prescribing cascades. METHODS: Three rounds of a modified Delphi process were conducted with a multidisciplinary panel of 38 clinicians from six countries with expertise in geriatric pharmacotherapy. The clinical importance of 139 prescribing cascades was assessed in Round 1. Cascades highly rated by ≥ 70% of panelists were included in subsequent rounds. Factors influencing ratings in Rounds 1 and 3 were categorized. After three Delphi rounds, highly rated prescribing cascades were reviewed by the study team to determine the final list of clinically important cascades consistent with potentially inappropriate prescribing. RESULTS: After three rounds, 13 prescribing cascades were highly rated by panelists. Following a study team review, the final tool includes nine clinically important prescribing cascades consistent with potentially inappropriate prescribing. Panelists reported that their ratings were influenced by many factors (e.g., how commonly they encountered the medications involved and the cascade itself, the severity of side effects, availability of alternatives). The relative importance of these factors in determining clinical importance varied by panelist. CONCLUSIONS: A nine-item consensus-based list of clinically important prescribing cascades, representing potentially inappropriate prescribing, was developed. Panelists' decisions about what constituted a clinically important prescribing cascade were multi-factorial. This tool not only raises awareness about these cascades but will also help clinicians recognize these and other important prescribing cascades. This list contributes to the prevention and management of polypharmacy and medication-related harm in older people.

Genomic Prediction of Complex Traits in Forage Plants Species: Perennial Grasses Case.

The majority of forage grass species are obligate outbreeders. Their breeding classically consists of an initial selection on spaced plants for highly heritable traits such as disease resistances and heading date, followed by familial selection on swards for forage yield and quality traits. The high level of diversity and heterozygosity, and associated decay of linkage disequilibrium (LD) over very short genomic distances, has hampered the implementation of genomic selection (GS) in these species. However, next generation sequencing technologies in combination with the development of genomic resources have recently facilitated implementation of GS in forage grass species such as perennial ryegrass (Lolium perenne L.), switchgrass (Panicum virgatum L.), and timothy (Phleum pratense L.). Experimental work and simulations have shown that GS can increase significantly the genetic gain per unit of time for traits with different levels of heritability. The main reasons are (1) the possibility to select single plants based on their genomic estimated breeding values (GEBV) for traits measured at sward level, (2) a reduction in the duration of selection cycles, and less importantly (3) an increase in the selection intensity associated with an increase in the genetic variance used for selection. Nevertheless, several factors should be taken into account for the successful implementation of GS in forage grasses. For example, it has been shown that the level of relatedness between the training and the selection population is particularly critical when working with highly structured meta-populations consisting of several genetic groups. A sufficient number of markers should be used to estimate properly the kinship between individuals and to reflect the variability of major QTLs. It is also important that the prediction models are trained for relevant environments when dealing with traits with high genotype × environment interaction (G × E). Finally, in these outbreeding species, measures to reduce inbreeding should be used to counterbalance the high selection intensity that can be achieved in GS.

Cost-effectiveness of a structured medication review approach for multimorbid older adults: Within-trial analysis of the OPERAM study.

BACKGROUND: Inappropriate 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. METHODS: We 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. RESULTS: Trial-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. CONCLUSION: We 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.

No Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials.

CONTEXT: Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age. OBJECTIVE: The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism. METHODS: This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months. RESULTS: Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 ±â€…1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (-0.03 g/dL [95% CI, -0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (-0.33 g/dL [95% CI, -0.87 to 0.21]). CONCLUSION: In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia.

Appropriateness of aspirin prescribing for primary and secondary prevention of cardiovascular disease in type 2 diabetes in different care settings.

BACKGROUND: Type 2 diabetes is associated with an increased cardiovascular risk. Use of aspirin has been shown to be of benefit for secondary prevention of cardiovascular disease in patients with type 2 diabetes; benefits in primary prevention have not been clearly proven. AIMS: This study aims to (a) determine if aspirin is prescribed appropriately in type 2 diabetes for primary or secondary prevention of cardiovascular disease (CVD) and (b) evaluate whether there are differences in aspirin prescribing according to where people receive their care. DESIGN: Cross-sectional study METHODS: The medical records of individuals with type 2 diabetes aged over 18 years and attending Elmwood Primary Care Centre and Cork University Hospital Diabetes outpatient clinics (n = 400) between February and August 2017 were reviewed. RESULTS: There were 90 individuals exclusively attending primary care and 310 persons attending shared care. Overall, 49.0% (n = 196) of those were prescribed aspirin, of whom 42.3% were using it for secondary prevention. Aspirin was used significantly more in people attending shared care (p < 0.001). About 10.8% of individuals with diabetes and CVD attending shared care met guidelines for, but were not prescribed aspirin. CONCLUSION: A significant number of people with type 2 diabetes who should have been prescribed aspirin for secondary prevention were not receiving it at the time of study assessment. In contrast, a substantial proportion who did not meet criteria for aspirin use was prescribed it for primary prevention.