Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales.

Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term "non-carbapenemase (NCP)", particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.

Molecular Rapid Diagnostics Improve Time to Effective Therapy and Survival in Patients with Vancomycin-Resistant Enterococcus Bloodstream Infections.

Delays in appropriate antibiotic therapy are a key determinant for deleterious outcomes among patients with vancomycin-resistant Enterococcus (VRE) bloodstream infections (BSIs). This was a multi-center pre/post-implementation study, assessing the impact of a molecular rapid diagnostic test (Verigene® GP-BC, Luminex Corporation, Northbrook, IL, USA) on outcomes of adult patients with VRE BSIs. The primary outcome was time to optimal therapy (TOT). Multivariable logistic and Cox proportional hazard regression models were used to determine the independent associations of post-implementation, TOT, early vs. delayed therapy, and mortality. A total of 104 patients with VRE BSIs were included: 50 and 54 in the pre- and post-implementation periods, respectively. The post- vs. pre-implementation group was associated with a 1.8-fold faster rate to optimized therapy (adjusted risk ratio, 1.841 [95% CI 1.234-2.746]), 6-fold higher likelihood to receive early effective therapy (<24 h, adjusted odds ratio, 6.031 [2.526-14.401]), and a 67% lower hazards for 30-day in-hospital mortality (adjusted hazard ratio, 0.322 [0.124-1.831]), after adjusting for age, sex, and severity scores. Inversely, delayed therapy was associated with a 10-fold higher risk of in-hospital mortality (aOR 10.488, [2.497-44.050]). Reduced TOT and in-hospital mortality were also observed in subgroups of immunosuppressed patients in post-implementation. These findings demonstrate that the addition of molecular rapid diagnostic tests (mRDT) to clinical microbiology and antimicrobial stewardship practices are associated with a clinically significant reduction in TOT, which is associated with lower mortality for patients with VRE BSIs, underscoring the importance of mRDTs in the management of VRE infections.

Metformin Attenuates Inflammatory Responses and Enhances Antibody Production in an Acute Pneumonia Model of Streptococcus pneumoniae.

Metformin may potentially reverse various age-related conditions; however, it is unclear whether metformin can also mitigate or delay the deterioration of immunological resilience that occurs in the context of infections that are commonly observed in older persons. We examined whether metformin promotes the preservation of immunological resilience in an acute S. pneumoniae (SPN) infection challenge in young adult mice. Mice were fed metformin (MET-alone) or standard chow (controls-alone) for 10 weeks prior to receiving intratracheal inoculation of SPN. A subset of each diet group received pneumococcal conjugate vaccine at week 6 (MET + PCV and control + PCV). Compared to controls-alone, MET-alone had significantly less infection-associated morbidity and attenuated inflammatory responses during acute SPN infection. Metformin lowered the expression of genes in the lungs related to inflammation as well as shorter lifespan in humans. This was accompanied by significantly lower levels of pro-inflammatory cytokines (e.g., IL6). MET + PCV vs. control + PCV manifested enhanced SPN anticapsular IgM and IgG levels. The levels of SPN IgM production negatively correlated with expression levels of genes linked to intestinal epithelial structure among MET + PCV vs. control + PCV groups. Correspondingly, the gut microbial composition of metformin-fed mice had a significantly higher abundance in the Verrucomicrobia, Akkermansia muciniphila, a species previously associated with beneficial effects on intestinal integrity and longevity. Together, these findings indicate metformin's immunoprotective potential to protect against infection-associated declines in immunologic resilience.

Predominance of Non-carbapenemase Producing Carbapenem-Resistant Enterobacterales in South Texas.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) pose a significant global public health threat. Resistance among CRE is particularly complex, owing to numerous possible resistance mechanisms and broad definitions. We aimed to characterize the clinical and molecular profiles of CRE in the South Texas region. MATERIALS AND METHODS: We compared the clinical, genotypic, and phenotypic profiles of carbapenemase producing Enterobacterales (CPE) with those of non-carbapenemase producers (NCPE) isolated from South Texas, United States between 2011 and 2019. Molecular characteristics and resistance mechanisms were analyzed using whole-genome sequences. RESULTS: The majority (59%) of the CRE isolates were NCPE while 41% of isolates harbored carbapenemases, predmonantly bla KPC-type. The most common CPE was Klebsiella pneumoniae while majority of Enterobacter cloacae and Escherichia coli were NCPE Among K. pneumoniae, the clonal group 307 has emerged as a predmoninant group and was associated with as many CRE infections as the previous common clonal group 258. Patients with NCPE compared to CPE infections were associated with higher antimicrobial exposure prior to culture collection (days of therapy, 795 vs. 242; p < 0.001) and emergency department visits within past 90 days (22% vs. 4%; p = 0.011). The all cause 30-day mortality was 21%. CONCLUSIONS: This study highlights the diversity of resistance mechanisms underlying CRE in South Texas, with 59% not harboring a carbapenemase. Individuals with NCPE infections were more likely to have had prior antimicrobial therapy and emergency department visits compared to those with CPE. Identification and distinction of these mechanisms by rapid identification of species and carbapenemase would allow for optimal treatment and infection control efforts.

The Health System Costs of Potentially Inappropriate Prescribing: A Population-Based, Retrospective Cohort Study Using Linked Health Administrative Databases in Ontario, Canada.

OBJECTIVE: The aim of this study was to determine the health system costs from hospitalizations, emergency department (ED) visits, and medications due to potentially inappropriate prescribing (PIP) in Ontario, Canada, at the population-level. METHODS: A retrospective cohort of individuals ≥ 66 years of age and prescribed at least one medication from April 2002 to March 2015 was identified using linked population-level health administrative databases from Ontario, Canada. Patients were identified as having PIP or no PIP by applying a subset of the Screening Tool of Older Persons' Potentially Inappropriate Prescribing/Screening Tool to Alert Doctors to Right Treatment (STOPP/START) criteria. The number of days spent in hospital, new medications prescribed, and ED visits in the 90 days following PIP or patient index date were captured, as well as the total costs from each of these health services. Count regression models were used to generate incidence rate ratios (IRRs) for each outcome given the presence of PIP versus no PIP and combined with the prevalence of PIP to generate population attributable fractions (PAFs). The PAF was then multiplied by the cost for each health service to obtain the costs attributable to PIP in the whole cohort, and by age and sex. RESULTS: PIP was associated with an increased rate of hospitalization (IRR 2.77, 95% confidence interval [CI] 2.72-2.82), ED visits (IRR 1.87, 95% CI 1.82-1.92), and newly prescribed medications (IRR 1.13, 95% CI 1.13-1.14), resulting in PAFs of 55.7, 37.9, and 5.0% for each outcome, respectively. PIP was associated with 38.8% of the total spent on these healthcare services ($1.22 billion) in the 90 days after PIP. Costs attributable to PIP decreased with age despite increasing prevalence. CONCLUSIONS: PIP in older adults is a significant source of health system costs from healthcare service use beyond medication costs, with a significant portion of hospitalizations and ED visit costs attributable to PIP. Future work should focus on identifying strategies and priorities for intervention.

Gut Microbiome: Profound Implications for Diet and Disease.

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual's starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.

Health care providers' roles and responsibilities in management of polypharmacy: Results of a modified Delphi.

BACKGROUND: Little is known about the roles that allow interprofessional teams to effectively manage older patients experiencing polypharmacy. OBJECTIVES: To identify and examine the consensus on salient interprofessional roles, responsibilities and competencies required in managing polypharmacy. METHODS: Four focus groups with 35 team members practising in geriatrics were generated to inform survey development. The sessions generated 63 competencies, roles or responsibilities, which were categorized into 4 domains defined by the Canadian Interprofessional Health Collaborative. The resulting survey was administered nationally to geriatric health care professionals who were asked to rate the importance of each item in managing polypharmacy; we sought agreement within and across professions using a confirmatory 2-round Delphi method. RESULTS: Round 1 was completed by 98 survey respondents and round 2 by 72. There was high intra-professional and interprofessional consensus regarding the importance of competencies among physicians, nurses and pharmacists; though pharmacists rated fewer competencies as important. Less consensus was observed among other health care professionals or they indicated the nonimportance of competencies despite focus group discussion to the contrary. DISCUSSION: Although there is a strong consensus of polypharmacy management competencies across team members who have been more traditionally involved in medication management, there continue to be health care providers with differing understandings of competencies that may contribute to reduced reliance on medication. Lower importance ratings suggest pharmacists may not acknowledge or recognize their own potential roles in interprofessional polypharmacy management. CONCLUSION: Further exploration to understand the underutilization of professional expertise in managing polypharmacy will contribute to refining role clarity and translating competencies in practical settings, as well as guiding educators regarding curricular content.

Interprovincial Variation of Psychotropic Prescriptions Dispensed to Older Canadian Adults.

BACKGROUND: Utilization of psychotropic medications among the elderly has garnered attention due to concerns about safety and degree of efficacy, but may be used differently across regions. METHODS: We conducted a cross-sectional study of all antipsychotic, benzodiazepine, and trazodone prescriptions dispensed to seniors ( ≥ 65 years) leveraging IQVIA (Durham, NC) GPM data in 2013. We report the units dispensed (per 100 seniors) by province. RESULTS: Nationally, on average, 26,210 units of antipsychotics, 24,257 of benzodiazepines, and 7,519 of trazodone were dispensed in 2013 for every 100 seniors; reports varied across Canada. The rate of antipsychotic and benzodiazepine prescribing was highest in New Brunswick (AP: 35,375 units per 100, BZD: 43,989 units per 100), and lowest in Newfoundland & Labrador for antipsychotics (20,974 per 100) and Saskatchewan for benzodiazepines (12,692 per 100). Trazodone unit dispensation rates were highest in Nova Scotia (9,164 per 100) and lowest in Newfoundland & Labrador (2,968 per 100). CONCLUSIONS: There is considerable geographic variation in the prescribing patterns of antipsychotics, benzodiazepine, and trazodone. This study serves as the first step in understanding these differences, while future work is needed to develop region-specific strategies to optimize the prescribing of psychotropic medications to older Canadian adults.

Comparative, cross-sectional study of the format, content and timing of medication safety letters issued in Canada, the USA and the UK.

OBJECTIVES: To assess consistency in the format and content, and overlap of subject and timing, of medication safety letters issued by regulatory health authorities to healthcare providers in Canada, the USA and the UK. DESIGN: A cross-sectional study comparing medication safety letters issued for the purpose of alerting healthcare providers to newly identified medication problems associated with medications already on the market. SETTING: Online databases operated by Health Canada, the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency were searched to select medication safety letters issued between 1 January 2010 and 31 December 2014. Format, content and timing of each medication safety letter were assessed using an abstraction tool comprising 21 characteristics deemed relevant by consensus of the research team. MAIN OUTCOME MEASURES: Main outcome measures included, first, characteristics (format and content) of medication safety letters and second, overlap of subject and release date across countries. RESULTS: Of 330 medication safety letters identified, 227 dealt with unique issues relating to medications available in all three countries. Of these 227 letters, 21 (9%) medication problems were the subject of letters released in all three countries; 40 (18%) in two countries and 166 (73%) in only one country. Only 13 (62%) of the 21 letters issued in all three countries were released within 6 months of each other. CONCLUSIONS: Significant discrepancies in both the subject and timing of medication safety letters issued by health authorities in three countries (Canada, the USA and the UK) where medical practice is otherwise comparable, raising questions about why, how and when medication problems are identified and communicated to healthcare providers by the authorities. More rapid communication of medication problems and better alignment between authorities could enhance patient safety.

Health system costs of potentially inappropriate prescribing in Ontario, Canada: a protocol for a population-based cohort study.

INTRODUCTION: Adverse drug events (ADEs) are common in older persons and contribute significantly to emergency department visits, hospitalisations and mortality. ADEs are often due to potentially inappropriate prescriptions (PIP) or potentially inappropriate omissions (PIO), and are avoidable if inappropriate prescriptions or omissions are identified and prevented. Identifying PIP/PIO at the population level through the application of PIP/PIO assessment tools to health administrative data can provide a unique opportunity to assess the economic burden of PIP/PIO on the healthcare system beyond medication costs which is yet to be done. The objective of this study is to assess the economic burden associated with PIP/PIO and to estimate the incremental costs associated with distinct PIP/PIO in the province of Ontario. METHODS AND ANALYSIS: We will conduct a retrospective cohort study using Ontario's health administrative databases. Eligible patients aged 66 years and older who were prescribed at least one medication between 1 April 2003 and 31 March 2014 (approximately 2.4 million patients) will be included. Population attributable fraction methodology will be used to assess the overall burden of PIP in Ontario, while regression analyses will be used to estimate the incremental costs of having specific PIP criteria and aid in prioritising targets for intervention. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at Sunnybrook Health Sciences Centre, Toronto, Canada. Dissemination will occur via publication, presentation at national and international conferences, and knowledge exchange with various stakeholders.

Patient Values and Preferences Surrounding Proton Pump Inhibitor Use: A Scoping Review.

BACKGROUND: Proton pump inhibitors (PPIs) treat various upper gastrointestinal (GI) diseases. Around 50% of patients may remain on PPIs long-term without ongoing need. Eligible patients should be offered the choice of continuing their PPI or trying to reduce/stop their PPI (deprescribing), a choice dependent on values and preferences. OBJECTIVES: Our objective was to systematically scope the available evidence on patient values and preferences surrounding continued PPI treatment and/or the decision to try a reduction in their PPI. We searched the MEDLINE, Embase, and Cochrane Library databases and the grey literature as of 9 August 2016 for studies of any design examining patient values and preferences toward PPI treatment and/or deprescribing. We included patients aged ≥18 years taking PPIs for upper GI diseases. RESULTS: We located 12 eligible studies (seven surveys, four qualitative studies, one randomized controlled trial). One study only examined values and preferences towards reducing PPI use, five studies looked only at PPI treatment (initiation/continuation), four studies assessed both PPI treatment and reduction, and two studies evaluated PPI treatment and switching (to alternative PPIs). Patients value symptom control highly and worry about symptoms returning if the PPI is reduced. They are encouraged to consider reducing their PPI if a clinician provides advice and education. All five studies that examined reducing PPI use suggest patients should understand the rationale for considering continuation versus deprescribing of PPIs and should know what to expect from deprescribing. Patients are encouraged by knowing they can return to their previous dose if necessary. Our results were limited by the small sizes of studies and the heterogeneous populations. CONCLUSION: Patients are willing to discuss the option of continuing PPI use or trying to reduce their PPI; however, a range of attitudes exist. The results suggest that reducing a PPI is a preference-sensitive decision. Therefore, patient attitudes should be elicited and incorporated into shared decision making surrounding the decision to continue or try deprescribing a PPI, and structured tools will be helpful to encourage this.

Deprescribing antihyperglycemic agents in older persons: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper, stop, or switch antihyperglycemic agents in older adults. METHODS: We focused on the highest level of evidence available and sought input from primary care professionals in guideline development, review, and endorsement processes. Seven clinicians (2 family physicians, 3 pharmacists, 1 nurse practitioner, and 1 endocrinologist) and a methodologist comprised the overall team; members disclosed conflicts of interest. We used a rigorous process, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, for guideline development. We conducted a systematic review to assess evidence for the benefits and harms of deprescribing antihyperglycemic agents. We performed a review of reviews of the harms of continued antihyperglycemic medication use, and narrative syntheses of patient preferences and resource implications. We used these syntheses and GRADE quality-of-evidence ratings to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. A decision-support algorithm was developed to accompany the guideline. RECOMMENDATIONS: We recommend deprescribing antihyperglycemic medications known to contribute to hypoglycemia in older adults at risk or in situations where antihyperglycemic medications might be causing other adverse effects, and individualizing targets and deprescribing accordingly for those who are frail, have dementia, or have a limited life expectancy. CONCLUSION: This guideline provides practical recommendations for making decisions about deprescribing antihyperglycemic agents. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Déprescription des antihyperglycémiants chez les personnes âgées: Guide de pratique clinique fondé sur les données probantes.

OBJECTIF: Formuler des lignes directrices fondées sur les données probantes afin d'aider les cliniciens à décider du moment et de la façon sécuritaire de réduire la dose des antihyperglycémiants, de mettre fin au traitement ou de passer à un autre agent chez les personnes âgées. MÉTHODES: Nous nous sommes concentrés sur les données les plus probantes disponibles et avons cherché à obtenir les commentaires des professionnels de première ligne durant le processus de rédaction, de révision et d'adoption des lignes directrices. L'équipe était formée de 7 professionnels de la santé (2 médecins de famille, 3 pharmaciens, 1 infirmière praticienne et 1 endocrinologue) et d'une spécialiste de la méthodologie; les membres ont divulgué tout conflit d'intérêts. Nous avons eu recours à un processus rigoureux, y compris l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour formuler les lignes directrices. Nous avons effectué une revue systématique dans le but d'évaluer les données probantes indiquant les bienfaits et les torts liés à la déprescription des antihyperglycémiants. Nous avons révisé les revues des torts liés à la poursuite du traitement antihyperglycémiant, et effectué des synthèses narratives des préférences des patients et des répercussions sur les ressources. Ces synthèses et évaluations de la qualité des données selon l'approche GRADE ont servi à formuler les recommandations. L'équipe a peaufiné le texte sur le contenu et les recommandations des lignes directrices par consensus et a synthétisé les considérations cliniques afin de répondre aux questions courantes des cliniciens de première ligne. Une version préliminaire des lignes directrices a été distribuée aux cliniciens et aux intervenants aux fins d'examen, et des révisions ont été apportées au texte à chaque étape. Un algorithme d'appui décisionnel a été conçu pour accompagner les lignes directrices. RECOMMANDATIONS: Nous recommandons de déprescrire les antihyperglycémiants reconnus pour contribuer à l'hypoglycémie chez les personnes âgées à risque ou dans les situations où les antihyperglycémiants pourraient causer d'autres effets indésirables, et d'individualiser les cibles et de déprescrire en conséquence chez les personnes frêles, atteintes de démence ou dont l'espérance de vie est limitée. CONCLUSION: Les présentes lignes directrices émettent des recommandations pratiques pour décider du moment et de la façon de déprescrire les antihyperglycémiants. Elles visent à contribuer au processus de décision conjointement avec le patient et non à le dicter.

Lack of Evidence to Guide Deprescribing of Antihyperglycemics: A Systematic Review.

INTRODUCTION: Individualizing glycemic targets to goals of care and time to benefit in persons with type 2 diabetes is good practice, particularly in populations at risk of hypoglycemia and adverse outcomes relating to the use of antihyperglycemics. Guidelines acknowledge the need for relaxed targets in frail older adults, but there is little guidance on how to safely deprescribe (i.e. stop, reduce or substitute) antihyperglycemics. METHODS: The purpose of this study was to synthesize evidence from all studies evaluating the effects of deprescribing versus continuing antihyperglycemics in older adults with type 2 diabetes. To this end, we searched MEDLINE, EMBASE, and Cochrane Library (July 2015) for controlled studies evaluating the effects of deprescribing antihyperglycemics in adults with type 2 diabetes. All such studies were eligible for inclusion in our study, and two independent reviewers screened titles, abstracts and full-text articles, extracted data, and evaluated risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment and a narrative summary were completed. RESULTS: We identified two controlled before-and-after studies, both of very low quality. One study found that an educational intervention decreased glyburide use while not compromising glucose control. The other reported that cessation of antihyperglycemics in elderly nursing home patients resulted in a non-significant increase in glycated hemoglobin (HbA1C). No significant change in hypoglycemia rate was found in the only study with this outcome measure. CONCLUSIONS: There is limited evidence available regarding deprescribing antihyperglycemic medications. Adequately powered, high-quality studies, particularly in the elderly and with clinically important outcomes, are required to support evidence-based decision-making. PROTOCOL REGISTRATION NUMBER: CRD42015017748.

Diffusion of Innovations model helps interpret the comparative uptake of two methodological innovations: co-authorship network analysis and recommendations for the integration of novel methods in practice.

OBJECTIVE: The objective of this study was to characterize the diffusion of methodological innovation. STUDY DESIGN AND SETTING: Comparative case study analysis of the diffusion of two methods that summarize confounder information into a single score: disease risk score (DRS) and high-dimensional propensity score (hdPS). We completed systematic searches to identify DRS and hdPS papers in the field of pharmacoepidemiology through to the end of 2013, plotted the number of papers and unique authors over time, and created sociograms and animations to visualize co-authorship networks. First and last author affiliations were used to ascribe institutional contributions to each paper and network. RESULTS: We identified 43 DRS papers by 153 authors since 1981, reflecting slow uptake during initial periods of uncertainty and broader diffusion since 2001 linked to early adopters from Vanderbilt. We identified 44 hdPS papers by 147 authors since 2009, reflecting rapid and integrated diffusion, likely facilitated by opinion leaders, early presentation at conferences, easily accessible statistical code, and improvement in funding. Most contributions (87% DRS, 96% hdPS) were from North America. CONCLUSION: When proposing new methods, authors are encouraged to consider innovation attributes and early evaluation to improve knowledge translation of their innovations for integration into practice, and we provide recommendations for consideration.

Effect of a Proton Pump Inhibitor Deprescribing Guideline on Drug Usage and Costs in Long-Term Care.

OBJECTIVES: To assess the effect of a proton pump inhibitor (PPI) deprescribing guideline on PPI usage and PPI drug costs in one long-term care home in Ontario, Canada. DESIGN: Interrupted time-series analysis to compare monthly PPI usage and average monthly PPI cost per resident 9 months before guideline implementation to 12 months after. SETTING: One long-term care home in Ottawa, Ontario, Canada. PARTICIPANTS: Long-term care residents prescribed a PPI over a 21-month period (n = 335). INTERVENTION: PPI deprescribing guideline and decision support tool used during quarterly medication reviews. MEASUREMENTS: (1) Total number of PPI prescriptions (PPI usage) and (2) average PPI drug cost per resident. We also measured the proportion of residents whose PPI was deprescribed in the preguideline period and postguideline period. RESULTS: The deprescribing guideline was associated with a decrease in PPI usage but the association was not statistically significant (-8.7 prescriptions, 95% confidence interval [CI] -22.0 to 4.6). The PPI guideline led to a significant decrease in average monthly PPI drug cost per resident over time (0.16 CAD reduction per month; 95% CI -0.29 to -0.03). In the 9 months before intervention, 57 (27.8%) of 205 eligible residents had their PPI deprescribed, and in the 12 months after intervention 134 (50.0%) of 268 eligible residents had their PPI deprescribed (difference in proportions of 22.2%; 95% CI 13.4-30.4). DISCUSSION/CONCLUSION: The deprescribing guideline was associated with a decline PPI usage; however, this negative association was not statistically significant. PPI usage declined in the initial 6 months after guideline implementation but began to climb back to baseline after this, which may explain the lack of a significant reduction in PPI usage. This suggests that it was difficult to maintain PPI deprescribing efforts long-term. Although implementation of a PPI deprescribing guideline may lead to an initial reduction in PPI usage, and a significant reduction in the average cost of PPI prescriptions over time, it is imperative to explore ways to sustain deprescribing guideline use.

Potentially inappropriate prescribing (PIP) in long-term care (LTC) patients: validation of the 2014 STOPP-START and 2012 Beers criteria in a LTC population--a protocol for a cross-sectional comparison of clinical and health administrative data.

INTRODUCTION: Potentially inappropriate prescribing (PIP) is frequent and problematic in older patients. Identifying PIP is necessary to improve prescribing quality; ideally, this should be performed at the population level. Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Beers criteria were developed to identify PIP in clinical settings and are useful at the individual patient level; however, they are time-consuming and costly to apply. Only a subset of these criteria is applicable to routinely collected population-level health administrative data (HAD) because the clinical information necessary to implement these tools is often missing from databases. The performance of subsets of STOPP/START and Beers criteria in HAD compared with clinical data from the same patients is unknown; furthermore, the performance of the updated 2014 STOPP-START and 2012 Beers criteria compared with one another is also unknown. METHODS AND ANALYSIS: A cross-sectional study of linked HAD and clinical data will be conducted to validate the subsets of STOPP/START and Beers criteria applicable to HAD by comparing their performance when applied to clinical and HAD for the same patients. Eligible patients will be 66 years and over and recently admitted to 1 of 6 long-term care facilities in Ottawa, Ontario. The target sample size is 275, but may be less if statistical significance can be achieved sooner. Medication, diagnostic and clinical data will be collected by a consultant pharmacist. The main outcome measure is the proportion of PIP missed by the subset of STOPP/START and Beers criteria applied to HAD when compared with clinical data. ETHICS AND DISSEMINATION: The study was approved by the Ottawa Health Services Network Research Ethics Board, the Bruyère Continuing Care Research Ethics Board and the ethics board of the City of Ottawa Long Term Care Homes. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders. TRIAL REGISTRATION NUMBER: NCT02523482.