Supporting deprescribing in hospitalised patients: formative usability testing of a computerised decision support tool.

BACKGROUND: Despite growing evidence that deprescribing can improve clinical outcomes, quality of life and reduce the likelihood of adverse drug events, the practice is not widespread, particularly in hospital settings. Clinical risk assessment tools, like the Drug Burden Index (DBI), can help prioritise patients for medication review and prioritise medications to deprescribe, but are not integrated within routine care. The aim of this study was to conduct formative usability testing of a computerised decision support (CDS) tool, based on DBI, to identify modifications required to the tool prior to trialling in practice. METHODS: Our CDS tool comprised a DBI MPage in the electronic medical record (clinical workspace) that facilitated review of a patient's DBI and medication list, access to deprescribing resources, and the ability to deprescribe. Two rounds of scenario-based formative usability testing with think-aloud protocol were used. Seventeen end-users participated in the testing, including junior and senior doctors, and pharmacists. RESULTS: Participants expressed positive views about the DBI CDS tool but testing revealed a number of clear areas for improvement. These primarily related to terminology used (i.e. what is a DBI and how is it calculated?), and consistency of functionality and display. A key finding was that users wanted the CDS tool to look and function in a similar way to other decision support tools in the electronic medical record. Modifications were made to the CDS tool in response to user feedback. CONCLUSION: Usability testing proved extremely useful for identifying components of our CDS tool that were confusing, difficult to locate or to understand. We recommend usability testing be adopted prior to implementation of any digital health intervention. We hope our revised CDS tool equips clinicians with the knowledge and confidence to consider discontinuation of inappropriate medications in routine care of hospitalised patients. In the next phase of our project, we plan to pilot test the tool in practice to evaluate its uptake and effectiveness in supporting deprescribing in routine hospital care.

Shedding and survival of an intracellular pathogenic Endozoicomonas-like organism infecting king scallop Pecten maximus.

The Lyme Bay marine protected area (MPA) hosts a valuable population of king scallop Pecten maximus L. Recently, an Endozoicomonas-like organism (ELO), infecting host gill epithelial tissue, was associated with king scallop mass mortality events within the Lyme Bay MPA. Currently, very little is known about its transmission and survival outside the host. In this investigation, animals collected outside of reported mortality events showed high levels of ELO infection. Gill tissue disruption and the release of bacteria into the interlamellar space was seen histologically, suggesting shedding of ELO from host animals. To investigate pathogen survival outside the host, infected scallops were maintained in static water for a 24 h period, and then removed. Over the subsequent 8 d, water samples were collected and the quantity of ELO 16S rRNA transcript was measured by TaqManTM quantitative PCR (qPCR). The 16S rRNA transcript quantity was stable outside the host for 6 d before bacteria survival declined 2 logs (7.9 × 108 16S rRNA to 2.3 × 106 transcripts), suggesting that ELO can survive independently outside the host organism. The ELO-specific qPCR probe can therefore be used in future field studies of ELO prevalence within the environment and fauna of the Lyme Bay MPA.

Molecular Characterization of an Endozoicomonas-Like Organism Causing Infection in the King Scallop (Pecten maximus L.).

One of the fastest growing fisheries in the UK is the king scallop (Pecten maximus L.), also currently rated as the second most valuable fishery. Mass mortality events in scallops have been reported worldwide, often with the causative agent(s) remaining uncharacterized. In May 2013 and 2014, two mass mortality events affecting king scallops were recorded in the Lyme Bay marine protected area (MPA) in Southwest England. Histopathological examination showed gill epithelial tissues infected with intracellular microcolonies (IMCs) of bacteria resembling Rickettsia-like organisms (RLOs), often with bacteria released in vascular spaces. Large colonies were associated with cellular and tissue disruption of the gills. Ultrastructural examination confirmed the intracellular location of these organisms in affected epithelial cells. The 16S rRNA gene sequences of the putative IMCs obtained from infected king scallop gill samples, collected from both mortality events, were identical and had a 99.4% identity to 16S rRNA gene sequences obtained from "Candidatus Endonucleobacter bathymodioli" and 95% with Endozoicomonas species. In situ hybridization assays using 16S rRNA gene probes confirmed the presence of the sequenced IMC gene in the gill tissues. Additional DNA sequences of the bacterium were obtained using high-throughput (Illumina) sequencing, and bioinformatic analysis identified over 1,000 genes with high similarity to protein sequences from Endozoicomonas spp. (ranging from 77 to 87% identity). Specific PCR assays were developed and applied to screen for the presence of IMC 16S rRNA gene sequences in king scallop gill tissues collected at the Lyme Bay MPA during 2015 and 2016. There was 100% prevalence of the IMCs in these gill tissues, and the 16S rRNA gene sequences identified were identical to the sequence found during the previous mortality event.IMPORTANCE Molluscan mass mortalities associated with IMCs have been reported worldwide for many years; however, apart from histological and ultrastructural characterization, characterization of the etiological agents is limited. In the present work, we provide detailed molecular characterization of an Endozoicomonas-like organism (ELO) associated with an important commercial scallop species.

Arctic cyanobacterial mat community diversity decreases with latitude across the Canadian Arctic.

Cyanobacterial mats are commonly reported as hotspots of microbial diversity across polar environments. These thick, multilayered microbial communities provide a refuge from extreme environmental conditions, with many species able to grow and coexist despite the low allochthonous nutrient inputs. The visibly dominant phototrophic biomass is dependent on internal nutrient recycling by heterotrophic organisms within the mats; however, the specific contribution of heterotrophic protists remains little explored. In this study, mat community diversity was examined along a latitudinal gradient (55-83°N), spanning subarctic taiga, tundra, polar desert, and the High Arctic ice shelves. The prokaryotic and eukaryotic communities were targeted, respectively, by V4 16S ribosomal RNA (rRNA) and V9 18S rRNA gene amplicon high-throughput sequencing. Prokaryotic and eukaryotic richness decreased, in tandem with decreasing temperatures and shorter seasons of light availability, from the subarctic to the High Arctic. Taxonomy-based annotation of the protist community revealed diverse phototrophic, mixotrophic, and heterotrophic genera in all mat communities, with fewer parasitic taxa in High Arctic communities. Co-occurrence network analysis identified greater heterogeneity in eukaryotic than prokaryotic community structure among cyanobacterial mats across the Canadian Arctic. Our findings highlight the sensitivity of microbial eukaryotes to environmental gradients across northern high latitudes.

Impact of a Comprehensive Intervention Bundle Including the Drug Burden Index on Deprescribing Anticholinergic and Sedative Drugs in Older Acute Inpatients: A Non-randomised Controlled Before-and-After Pilot Study.

INTRODUCTION: Implementation of the Drug Burden Index (DBI) as a risk assessment tool in clinical practice may facilitate deprescribing. OBJECTIVE: The purpose of this study is to evaluate how a comprehensive intervention bundle using the DBI impacts (i) the proportion of older inpatients with at least one DBI-contributing medication stopped or dose reduced on discharge, compared with admission; and (ii) the changes in deprescribing of different DBI-contributing medication classes during hospitalisation. METHODS: This before-and-after study was conducted in an Australian metropolitan tertiary referral hospital. Patients aged ≥ 75 years admitted to the acute aged care service for ≥ 48 h from December 2020 to October 2021 and prescribed DBI-contributing medication were included. During the control period, usual care was provided. During the intervention, access to the intervention bundle was added, including a clinician interface displaying DBI score in the electronic medical record. In a subsequent 'stewardship' period, a stewardship pharmacist used the bundle to provide clinicians with patient-specific recommendations on deprescribing of DBI-contributing medications. RESULTS: Overall, 457 hospitalisations were included. The proportion of patients with at least one DBI-contributing medication stopped/reduced on discharge increased from 29.9% (control period) to 37.5% [intervention; adjusted risk difference (aRD) 6.5%, 95% confidence intervals (CI) -3.2 to 17.5%] and 43.1% (stewardship; aRD 12.1%, 95% CI 1.0-24.0%). The proportion of opioid prescriptions stopped/reduced rose from 17.9% during control to 45.7% during stewardship (p = 0.04). CONCLUSION: Integrating a comprehensive intervention bundle and accompanying stewardship program is a promising strategy to facilitate deprescribing of sedative and anticholinergic medications in older inpatients.

A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease.

Murine norovirus infection does not cause major disruptions in the murine intestinal microbiota.

BACKGROUND: Murine norovirus (MNV) is the most common gastrointestinal pathogen of research mice and can alter research outcomes in biomedical mouse models of inflammatory bowel disease (IBD). Despite indications that an altered microbiota is a risk factor for IBD, the response of the murine intestinal microbiota to MNV infection has not been examined. Microbiota disruption caused by MNV infection could introduce the confounding effects observed in research experiments. Therefore, this study investigated the effects of MNV infection on the intestinal microbiota of wild-type mice. RESULTS: The composition of the intestinal microbiota was assessed over time in both outbred Swiss Webster and inbred C57BL/6 mice following MNV infection. Mice were infected with both persistent and non-persistent MNV strains and tissue-associated or fecal-associated microbiota was analyzed by 16S rRNA-encoding gene pyrosequencing. Analysis of intestinal bacterial communities in infected mice at the phylum and family level showed no major differences to uninfected controls, both in tissue-associated samples and feces, and also over time following infection, demonstrating that the intestinal microbiota of wild-type mice is highly resistant to disruption following MNV infection. CONCLUSIONS: This is the first study to describe the intestinal microbiota following MNV infection and demonstrates that acute or persistent MNV infection is not associated with major disruptions of microbial communities in Swiss Webster and C57BL/6 mice.