Using implementation science to promote the use of the fascia iliaca blocks in hip fracture care.

PURPOSE: There is variable and suboptimal use of fascia iliaca compartment nerve blocks (FICBs) in hip fracture care. Our objective was to use an evidence-based and theory-informed implementation science approach to analyze barriers and facilitators to timely administration of FICB and select evidence-based interventions to enhance uptake. METHODS: We conducted a qualitative study at a single centre using semistructured interviews and site observations. We interviewed 35 stakeholders including health care providers, managers, patients, and caregivers. We mapped barriers and facilitators to the Theoretical Domains Framework (TDF) and Consolidated Framework for Implementation Research (CFIR). We compared the rate and timeliness of FICB administration before and after evidence-based implementation strategies were applied. RESULTS: The study identified 18 barriers and 11 facilitators within seven themes of influences of FICB use: interpersonal relationships between health care professionals; clinician knowledge and skills related to FICB; roles, responsibilities, and processes for delivering FICB; perceptions on using FICB for pain; patient and caregiver perceptions on using FICB for pain; communication of hip fracture care between departments; and resources for delivering FICBs. We mapped the behaviour change domains to eight implementation strategies: restructure the environment, create and distribute educational materials, prepare patients to be active participants, perform audits and give feedback, use local opinion leaders, use champions, train staff on FICB procedures, and mandate change. We observed an increase in the rates of FICBs administered (48% vs 65%) and a decrease in the median time to administration (1.63 vs 0.81 days). CONCLUSION: Our study explains why FICBs are underused and shows that the TDF and CFIR provide a framework to identify barriers and facilitators to FICB implementation. The mapped implementation strategies can guide institutions to improve use of FICB in hip fracture care.

RéSUMé: OBJECTIF: Il existe une utilisation variable et sous-optimale des blocs nerveux du compartiment fascia iliaca (FICB) dans les soins des fractures de la hanche. Notre objectif était d'utiliser une approche scientifique de la mise en œuvre fondée sur des données probantes et sur la théorie pour analyser les obstacles et les facilitateurs à l'administration opportune d'un FICB et pour sélectionner des interventions fondées sur des données probantes pour améliorer l'adoption de cette technique. MéTHODE: Nous avons mené une étude qualitative dans un seul centre à l'aide d'entrevues semi-structurées et d'observations sur place. Nous avons interviewé 35 intervenant·es, y compris des prestataires de soins de santé, des gestionnaires, des patient·es et des soignant·es. Nous avons cartographié les obstacles et les facilitateurs du cadre des domaines théoriques (Theoretical Domains Framework, TDF) et du cadre consolidé pour la recherche sur la mise en œuvre (Consolidated Framework for Implementation Research, CFIR). Nous avons comparé le taux et la rapidité d'administration d'un FICB avant et après l'application des stratégies de mise en œuvre fondées sur des données probantes. RéSULTATS: L'étude a identifié 18 obstacles et 11 facilitateurs dans sept thèmes d'influence de l'utilisation du FICB : les relations interpersonnelles entre les professionnel·les de la santé; les connaissances et les compétences des clinicien·nes liées au FICB; les rôles, responsabilités et processus d'exécution des FICB; les perceptions de l'utilisation des FICB pour soulager la douleur; les perceptions des patient·es et des soignant·es concernant l'utilisation de FICB pour soulager la douleur; la communication des soins des fractures de la hanche entre les services; et les ressources nécessaires à l'exécution des FICB. Nous avons mis en correspondance les domaines de changement de comportement avec huit stratégies de mise en œuvre : restructurer l'environnement, créer et distribuer du matériel éducatif, préparer les patient·es à participer activement, effectuer des audits et donner de la rétroaction, faire appel à des leaders d'opinion locales et locaux, utiliser des champion·nes, former le personnel sur les interventions de FICB et forcer au changement. Nous avons observé une augmentation des taux de FICB administrés (48% vs 65%) et une diminution du délai médian d'administration (1,63 vs 0,81 jour). CONCLUSION: Notre étude explique pourquoi les FICB sont sous-utilisés et montre que le TDF et le CFIR fournissent un cadre pour identifier les obstacles et les facilitateurs à la mise en œuvre des FICB. Les stratégies de mise en œuvre cartographiées peuvent aider les établissements à améliorer l'utilisation des FICB dans le traitement des fractures de la hanche.

Successful implementation of a quality improvement bundle to reduce opioid overprescribing following total hip and knee arthroplasty.

BACKGROUND: Opioid overprescribing is commonplace after total hip (THA) and total knee arthroplasty (TKA). Preliminary data demonstrated that approximately 32% of the opioids prescribed at discharge from our hospital following THA and TKA remain unused. This is a concern given that unused prescribed opioids are available for diversion and may result in misuse and abuse. METHODS: Pre-intervention data were collected between 1 November 2018 and 10 December 2018. An intervention bundle was then introduced, including education of patients and providers, a standardised pain management algorithm and an autopopulated discharge prescription. The aim of this quality improvement initiative was to reduce the amount of opioid (average oral morphine equivalents (OME)) dispensed (based on the discharge prescription provided) following THA and TKA at our institution by 15% by 1 April 2019. DESIGN: Using an interrupted time series design, the outcome measure was the amount of opioid (OME) dispensed from the discharge prescription provided. Process measures included the percentage of autopopulated discharge prescriptions, the percentage of patients receiving education at discharge and the percentage of nurses and residents receiving standardised education. Balancing measures included patient satisfaction with postoperative pain management, and the percentage of patients filling the second half of the part-fill or requiring a subsequent opioid prescription. RESULTS: With 600 patients identified, mean OME dispensed at discharge was reduced by 26.3% (from 522.2 to 384.9 mg) after our interventions started. Utilisation of autopopulated part-fill prescriptions was 95.8%. There was no change in patient satisfaction nor in the proportion of patients requiring an additional opioid prescription post-intervention. Only 39% of patients filled the second half of the part-fill prescription post-intervention. CONCLUSIONS: Mean OME dispensed at discharge per patient was reduced with no change in patient satisfaction after introduction of the intervention bundle.

Rapid access to N-(indol-2-yl)amides and N-(indol-3-yl)amides as unexplored pharmacophores.

Preparation of N-(indol-2-yl)amides and N-(indol-3-yl)amides are scarce in the scientific literature due to unstable intermediates impeding current reported syntheses. We have employed cheap and readily available substrates in the Curtius rearrangement of indole-3-carboxazide to afford N-(indol-3-yl)amides. The reaction is observed for alkyl and aryl carboxylic acids and both N-substituted or 1H-indole derivatives are tolerated. This approach was extended to the preparation of N-(indol-2-yl)amides from the corresponding indole-2-carboxazides.

The therapeutic potential of α7 nicotinic acetylcholine receptor (α7 nAChR) agonists for the treatment of the cognitive deficits associated with schizophrenia.

Homomeric α7 nicotinic acetylcholine receptors (α7 nAChRs) have implications in the regulation of cognitive processes such as memory and attention, and have shown promise as a therapeutic target for the treatment of the cognitive deficits associated with schizophrenia. Multiple α7 nAChR agonists have entered human trials; however, unfavorable side effects and pharmacokinetic issues have hindered the development of a clinical α7 nAChR agonist. Currently, EVP-6124 is in phase III clinical trials, and several other α7 nAChR agonists (GTS-21 and AQW051) are in earlier stages of development. This review will summarize the recent advances and failures of α7 nAChR agonists in clinical trials for the treatment of the aforementioned pathology.

DrugBank 4.0: shedding new light on drug metabolism.

DrugBank (http://www.drugbank.ca) is a comprehensive online database containing extensive biochemical and pharmacological information about drugs, their mechanisms and their targets. Since it was first described in 2006, DrugBank has rapidly evolved, both in response to user requests and in response to changing trends in drug research and development. Previous versions of DrugBank have been widely used to facilitate drug and in silico drug target discovery. The latest update, DrugBank 4.0, has been further expanded to contain data on drug metabolism, absorption, distribution, metabolism, excretion and toxicity (ADMET) and other kinds of quantitative structure activity relationships (QSAR) information. These enhancements are intended to facilitate research in xenobiotic metabolism (both prediction and characterization), pharmacokinetics, pharmacodynamics and drug design/discovery. For this release, >1200 drug metabolites (including their structures, names, activity, abundance and other detailed data) have been added along with >1300 drug metabolism reactions (including metabolizing enzymes and reaction types) and dozens of drug metabolism pathways. Another 30 predicted or measured ADMET parameters have been added to each DrugCard, bringing the average number of quantitative ADMET values for Food and Drug Administration-approved drugs close to 40. Referential nuclear magnetic resonance and MS spectra have been added for almost 400 drugs as well as spectral and mass matching tools to facilitate compound identification. This expanded collection of drug information is complemented by a number of new or improved search tools, including one that provides a simple analyses of drug-target, -enzyme and -transporter associations to provide insight on drug-drug interactions.

DrugBank 3.0: a comprehensive resource for 'omics' research on drugs.

DrugBank (http://www.drugbank.ca) is a richly annotated database of drug and drug target information. It contains extensive data on the nomenclature, ontology, chemistry, structure, function, action, pharmacology, pharmacokinetics, metabolism and pharmaceutical properties of both small molecule and large molecule (biotech) drugs. It also contains comprehensive information on the target diseases, proteins, genes and organisms on which these drugs act. First released in 2006, DrugBank has become widely used by pharmacists, medicinal chemists, pharmaceutical researchers, clinicians, educators and the general public. Since its last update in 2008, DrugBank has been greatly expanded through the addition of new drugs, new targets and the inclusion of more than 40 new data fields per drug entry (a 40% increase in data 'depth'). These data field additions include illustrated drug-action pathways, drug transporter data, drug metabolite data, pharmacogenomic data, adverse drug response data, ADMET data, pharmacokinetic data, computed property data and chemical classification data. DrugBank 3.0 also offers expanded database links, improved search tools for drug-drug and food-drug interaction, new resources for querying and viewing drug pathways and hundreds of new drug entries with detailed patent, pricing and manufacturer data. These additions have been complemented by enhancements to the quality and quantity of existing data, particularly with regard to drug target, drug description and drug action data. DrugBank 3.0 represents the result of 2 years of manual annotation work aimed at making the database much more useful for a wide range of 'omics' (i.e. pharmacogenomic, pharmacoproteomic, pharmacometabolomic and even pharmacoeconomic) applications.

SMPDB: The Small Molecule Pathway Database.

The Small Molecule Pathway Database (SMPDB) is an interactive, visual database containing more than 350 small-molecule pathways found in humans. More than 2/3 of these pathways (>280) are not found in any other pathway database. SMPDB is designed specifically to support pathway elucidation and pathway discovery in clinical metabolomics, transcriptomics, proteomics and systems biology. SMPDB provides exquisitely detailed, hyperlinked diagrams of human metabolic pathways, metabolic disease pathways, metabolite signaling pathways and drug-action pathways. All SMPDB pathways include information on the relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to detailed descriptions contained in the Human Metabolome Database (HMDB) or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All SMPDB pathways are accompanied with detailed descriptions, providing an overview of the pathway, condition or processes depicted in each diagram. The database is easily browsed and supports full text searching. Users may query SMPDB with lists of metabolite names, drug names, genes/protein names, SwissProt IDs, GenBank IDs, Affymetrix IDs or Agilent microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB's mapping interface. All of SMPDB's images, image maps, descriptions and tables are downloadable. SMPDB is available at: http://www.smpdb.ca.

A structural and functional analysis of alpha-glucan recognition by family 25 and 26 carbohydrate-binding modules reveals a conserved mode of starch recognition.

Starch-hydrolyzing enzymes lacking alpha-glucan-specific carbohydrate-binding modules (CBMs) typically have lowered activity on granular starch relative to their counterparts with CBMs. Thus, consideration of starch recognition by CBMs is a key factor in understanding granular starch hydrolysis. To this end, we have dissected the modular structure of the maltohexaose-forming amylase from Bacillus halodurans (C-125). This five-module protein comprises an N-terminal family 13 catalytic module followed in order by two modules of unknown function, a family 26 CBM (BhCBM26), and a family 25 CBM (BhCBM25). Here we present a comprehensive structure-function analysis of starch and alpha-glucooligosaccharide recognition by BhCBM25 and BhCBM26 using UV methods, isothermal titration calorimetry, and x-ray crystallography. The results reveal that the two CBMs bind alpha-glucooligosaccharides, particularly those containing alpha-1,6 linkages, with different affinities but have similar abilities to bind granular starch. Notably, these CBMs appear to recognize the same binding sites in granular starch. The enhanced affinity of the tandem CBMs for granular starch is suggested to be the main biological advantage for this enzyme to contain two CBMs. Structural studies of the native and ligand-bound forms of BhCBM25 and BhCBM26 show a structurally conserved mode of ligand recognition but through non-sequence-conserved residues. Comparison of these CBM structures with other starch-specific CBM structures reveals a generally conserved mode of starch recognition.