Developing a Tool for Auditing the Quality of Antibiotic Dispensing in Community Pharmacies: A Pilot Study

Background: The European Centre for Disease Prevention and Control describes the community pharmacist as the gatekeeper to the quality of antibiotic use. The pharmacist has the responsibility to guard safe and effective antibiotic use; however, little is known about how this is implemented in practice. Aims: To assess the feasibility of a method to audit the quality of antibiotic dispensing in community pharmacy practice and to explore antibiotic dispensing practices in Greece, Lithuania, Poland, and Spain. Methods: The Audit Project Odense methodology to audit antibiotic dispensing practice was adapted for use in community pharmacy practice. Community pharmacists registered antibiotic dispensing on a specifically developed registration chart and were asked to provide feedback on the registration method. Results: Altogether, twenty pharmacists were recruited in four countries. They registered a total of 409 dispenses of oral antibiotics. Generally, pharmacists were positive about the feasibility of implementing the registration chart in practice. The frequency of checking for allergies, contraindications and interactions differed largely between the four countries. Pharmacists provided little advice to patients. The pharmacists rarely contacted prescribers. Conclusion: This tool seems to make it possible to get a useful picture of antibiotic dispensing patterns in community pharmacies. Dispensing practice does not seem to correspond with EU guidelines according to these preliminary results

Causal inference for planning randomised critical care trials:Protocol for a scoping review

BACKGROUND: Randomised clinical trials in critical care are prone to inconclusiveness owing, in part, to undue optimism about effect sizes and suboptimal accounting for heterogeneous treatment effects. Planned predictive enrichment based on secondary critical care data (often very rich with respect to both data types and temporal granularity) and causal inference methods may help overcome these challenges, but no overview exists about their use to this end. METHODS: We will conduct a scoping review to assess the extent and nature of the use of causal inference from secondary data for planned predictive enrichment of randomised clinical trials in critical care. We will systematically search 10 general and specialty journals for reports published on or after 1 January 2018, of randomised clinical trials enrolling adult critically ill patients. We will collect trial metadata (e.g., recruitment period and phase) and, when available, information pertaining to the focus of the review (predictive enrichment based on causal inference estimates from secondary data): causal inference methods, estimation techniques and software used; types of patient populations; data provenance, types and models; and the availability of the data (public or not). The results will be reported in a descriptive manner. DISCUSSION: The outlined scoping review aims to assess the use of causal inference methods and secondary data for planned predictive enrichment in randomised critical care trials. This will help guide methodological improvements to increase the utility, and facilitate the use, of causal inference estimates when planning such trials in the future

Varmepumper og Lavtemperatur-fjernvarme - Rapportering fra to workshops

Denne rapport udgør et delbidrag af rapporteringen fra projektet ” Effektiv fjernvarme i fremtidens energisystem”, som under Energistyrelsens Energiforskningsprogram (EFP) udføres af et konsortium af EA-energianalyse, Systemanalyseafdelingen på Risø DTU, RAM-løse edb samt Fjernvarmens visionsudvalg nedsat under Dansk Fjernvarmeforening.Formålet med projektet er at belyse, hvordan fjernvarmens rolle i energiforsyningen kan udvikles på langt sigt gennem effektiv drift, anvendelse af ny teknologi samt dynamisk samspil med elmarkedet. En fremtidig udvikling mod et bæredygtigt energisystem vil kræve betydelige energibesparelser, herunder i rumopvarmningen. Dette vil alt andet lige mange steder føre til, at grundlaget for fjernvarmen vil ændre sig. Det er således centralt i projektet, at opstille en række scenarier for fjernvarmens fremtidige rolle i energisystemet, herunder at belyse hvad reducerede varmetab i fjernvarmenet og dynamisk anvendelse af kendte og nye energiteknologier kan betyde. Disse teknologier omfatter bl.a. varmepumper, geotermi, fjernkøling og varmelagring. Endvidere er formålet at belyse hvordan samspillet mellem elmarkedet og fjernvarmen kan effektiviseres, samt at pege på hvilke rammebetingelser der især er kritiske for fjernvarmens fortsatte udvikling og effektivisering.Som et led i analyserne i projektet er der afholdt to workshops om henholdsvis anvendelsen af varmepumper og lavtemperatur-fjernvarmenet. Denne rapport er en dokumentation af de to workshops, idet den indeholder program, deltagerliste, præsentationer og korte resumeer. I begge workshops deltog eksterne indledere parallelt med projektgruppens egne deltagere. Vi takker deltagerne for præsentationer og engageret deltagelse i diskussionerne

Identification and evolution of a plant cell wall specific glycoprotein glycosyl transferase, ExAD

Extensins are plant cell wall glycoproteins that act as scaffolds for the deposition of the main wall carbohydrate polymers, which are interlocked into the supramolecular wall structure through intra- and inter-molecular iso-di-tyrosine crosslinks within the extensin backbone. In the conserved canonical extensin repeat, Ser-Hyp(4), serine and the consecutive C4-hydroxyprolines (Hyps) are substituted with an α-galactose and 1–5 β- or α-linked arabinofuranoses (Arafs), respectively. These modifications are required for correct extended structure and function of the extensin network. Here, we identified a single Arabidopsis thaliana gene, At3g57630, in clade E of the inverting Glycosyltransferase family GT47 as a candidate for the transfer of Araf to Hyp-arabinofuranotriose (Hyp-β1,4Araf-β1,2Araf-β1,2Araf) side chains in an α-linkage, to yield Hyp-Araf(4) which is exclusively found in extensins. T-DNA knock-out mutants of At3g57630 showed a truncated root hair phenotype, as seen for mutants of all hitherto characterized extensin glycosylation enzymes; both root hair and glycan phenotypes were restored upon reintroduction of At3g57630. At3g57630 was named Extensin Arabinose Deficient transferase, ExAD, accordingly. The occurrence of ExAD orthologs within the Viridiplantae along with its’ product, Hyp-Araf(4), point to ExAD being an evolutionary hallmark of terrestrial plants and charophyte green algae

Health alliance for prudent prescribing and yield of antibiotics in a patient-centred perspective (HAPPY PATIENT): a before-and-after intervention and implementation study protocol

Background Excessive and inappropriate use of antibiotics is the most important driver of antimicrobial resistance. The aim of the HAPPY PATIENT project is to evaluate the adaptation of European Union (EU) recommendations on the prudent use of antimicrobials in human health by evaluating the impact of a multifaceted intervention targeting different categories of healthcare professionals (HCPs) on common community-acquired infectious diseases, especially respiratory and urinary tract infections. Methods/design HAPPY PATIENT was initiated in January 2021 and is planned to end in December 2023. The partners of this project include 15 organizations from 9 countries. Diverse HCPs (doctors, nurses, pharmacists, and pharmacy technicians) will be audited by the Audit Project Odense (APO) method before and after an intervention in four different settings: general practice, out of hours services, nursing homes and community pharmacies in four high antibiotic prescribing countries (France, Poland, Greece, and Spain) and one low prescribing country (Lithuania). About 25 individuals from each professional group will be recruited in each country, who will register at least 25 patients with community-acquired infections during each audit period. Shortly before the second registration participants will undertake a multifaceted intervention and will receive the results from the first registration to allow the identification of possible quality problems. At these meetings participants will receive training courses on enhancement of communication skills, dissemination of clinical guidelines with recommendations for diagnosis and treatment, posters for the waiting rooms, and leaflets for patients. The results of the second registration will be compared with those obtained in the first audit. Discussion HAPPY PATIENT is an EU-funded project aimed at contributing to the battle against antibiotic resistance through improvement of the quality of management of common community-acquired infections based on interventions by different types of HCPs. It is hypothesized that the use of multifaceted strategies combining active intervention will be effective in reducing inappropriate prescribing and dispensing of antibiotics.publishedVersio

Genomic Profiling of a Randomized Trial of Interferon-α versus Hydroxyurea in MPN Reveals Mutation-Specific Responses

Although somatic mutations influence the pathogenesis, phenotype, and outcome of myeloproliferative neoplasms (MPNs), little is known about their impact on molecular response to cytoreductive treatment. We performed targeted next-generation sequencing (NGS) on 202 pretreatment samples obtained from patients with MPN enrolled in the DALIAH trial (A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms; #NCT01387763), a randomized controlled phase 3 clinical trial, and 135 samples obtained after 24 months of therapy with recombinant interferon-alpha (IFNα) or hydroxyurea. The primary aim was to evaluate the association between complete clinicohematologic response (CHR) at 24 months and molecular response through sequential assessment of 120 genes using NGS. Among JAK2-mutated patients treated with IFNα, those with CHR had a greater reduction in the JAK2 variant allele frequency (median, 0.29 to 0.07; P < .0001) compared with those not achieving CHR (median, 0.27 to 0.14; P < .0001). In contrast, the CALR variant allele frequency did not significantly decline in those achieving CHR or in those not achieving CHR. Treatment-emergent mutations in DNMT3A were observed more commonly in patients treated with IFNα compared with hydroxyurea (P = .04). Furthermore, treatment-emergent DNMT3A mutations were significantly enriched in IFNα–treated patients not attaining CHR (P = .02). A mutation in TET2, DNMT3A, or ASXL1 was significantly associated with prior stroke (age-adjusted odds ratio, 5.29; 95% confidence interval, 1.59-17.54; P = .007), as was a mutation in TET2 alone (age-adjusted odds ratio, 3.03; 95% confidence interval, 1.03-9.01; P = .044). At 24 months, we found mutation-specific response patterns to IFNα: (1) JAK2- and CALR-mutated MPN exhibited distinct molecular responses; and (2) DNMT3A-mutated clones/subclones emerged on treatment