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AnteayerInterdisciplinares

Effectiveness of dexmedetomidine during surgery under general anaesthesia on patient-centred outcomes: a systematic review and Bayesian meta-analysis protocol

Por: Verret · M. · Le · J. B. P. · Lalu · M. M. · McIsaac · D. I. · Nicholls · S. · Turgeon · A. F. · Hutton · B. · Zivkovic · F. · Graham · M. · Le · M. · Geist · A. · Berube · M. · Gilron · I. · Poulin · P. · Daudt · H. · Martel · G. · McVicar · J. · Moloo · H. · Fergusson · D. A.
Introduction

Dexmedetomidine is a promising pharmaceutical strategy to minimise opioid use during surgery. Despite its growing use, it is uncertain whether dexmedetomidine can improve patient-centred outcomes such as quality of recovery and pain.

Methods and analysis

We will conduct a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL approximately in October 2023. We will include randomised controlled trials evaluating the impact of systemic intraoperative dexmedetomidine on patient-centred outcomes. Patient-centred outcome definition will be based on the consensus definition established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC). Our primary outcome will be the quality of recovery after surgery. Our secondary outcomes will be patient well-being, function, health-related quality of life, life impact, multidimensional assessment of postoperative acute pain, chronic pain, persistent postoperative opioid use, opioid-related adverse events, hospital length of stay and adverse events. Two reviewers will independently screen and identify trials and extract data. We will evaluate the risk of bias of trials using the Cochrane Risk of Bias Tool (RoB 2.0). We will synthesise data using a random effects Bayesian model framework, estimating the probability of achieving a benefit and its clinical significance. We will assess statistical heterogeneity with the tau-squared and explore sources of heterogeneity with meta-regression. We have involved patient partners, clinicians, methodologists, and key partner organisations in the development of this protocol, and we plan to continue this collaboration throughout all phases of this systematic review.

Ethics and dissemination

Our systematic review does not require research ethics approval. It will help inform current clinical practice guidelines and guide development of future randomised controlled trials. The results will be disseminated in open-access peer-reviewed journals, presented at conferences and shared among collaborators and networks.

PROSPERO registration number

CRD42023439896.

Perceptions on artificial intelligence-based decision-making for coexisting multiple long-term health conditions: protocol for a qualitative study with patients and healthcare professionals

Por: Gunathilaka · N. J. · Gooden · T. E. · Cooper · J. · Flanagan · S. · Marshall · T. · Haroon · S. · DElia · A. · Crowe · F. · Jackson · T. · Nirantharakumar · K. · Greenfield · S.
Introduction

Coexisting multiple health conditions is common among older people, a population that is increasing globally. The potential for polypharmacy, adverse events, drug interactions and development of additional health conditions complicates prescribing decisions for these patients. Artificial intelligence (AI)-generated decision-making tools may help guide clinical decisions in the context of multiple health conditions, by determining which of the multiple medication options is best. This study aims to explore the perceptions of healthcare professionals (HCPs) and patients on the use of AI in the management of multiple health conditions.

Methods and analysis

A qualitative study will be conducted using semistructured interviews. Adults (≥18 years) with multiple health conditions living in the West Midlands of England and HCPs with experience in caring for patients with multiple health conditions will be eligible and purposively sampled. Patients will be identified from Clinical Practice Research Datalink (CPRD) Aurum; CPRD will contact general practitioners who will in turn, send a letter to patients inviting them to take part. Eligible HCPs will be recruited through British HCP bodies and known contacts. Up to 30 patients and 30 HCPs will be recruited, until data saturation is achieved. Interviews will be in-person or virtual, audio recorded and transcribed verbatim. The topic guide is designed to explore participants’ attitudes towards AI-informed clinical decision-making to augment clinician-directed decision-making, the perceived advantages and disadvantages of both methods and attitudes towards risk management. Case vignettes comprising a common decision pathway for patients with multiple health conditions will be presented during each interview to invite participants’ opinions on how their experiences compare. Data will be analysed thematically using the Framework Method.

Ethics and dissemination

This study has been approved by the National Health Service Research Ethics Committee (Reference: 22/SC/0210). Written informed consent or verbal consent will be obtained prior to each interview. The findings from this study will be disseminated through peer-reviewed publications, conferences and lay summaries.

Healthcare providers’ perception towards utilization of health information applications and its associated factors in healthcare delivery in health facilities in Cape Coast Metropolis, Ghana

by Richard Okyere Boadu, Godwin Adzakpah, Nathan Kumasenu Mensah, Kwame Adu Okyere Boadu, Jonathan Kissi, Christiana Dziyaba, Rosemary Bermaa Abrefa

Background

Information and communication technology (ICT) has significantly advanced global healthcare, with electronic health (e-Health) applications improving health records and delivery. These innovations, including electronic health records, strengthen healthcare systems. The study investigates healthcare professionals’ perceptions of health information applications and their associated factors in the Cape Coast Metropolis of Ghana’s health facilities.

Methods

We used a descriptive cross-sectional study design to collect data from 632 healthcare professionals (HCPs), in the three purposively selected health facilities in the Cape Coast municipality of Ghana, in July 2022. Shapiro-Wilk test was used to check the normality of dependent variables. Descriptive statistics were used to report means with corresponding standard deviations for continuous variables. Proportions were also reported for categorical variables. Bivariate regression analysis was conducted to determine the factors influencing the Benefits of Information Technology (BoIT); Barriers to Information Technology Use (BITU); and Motives of Information Technology Use (MoITU) in healthcare delivery. Stata SE version 15 was used for the analysis. A p-value of less than 0.05 served as the basis for considering a statistically significant accepting hypothesis.

Results

Healthcare professionals (HCPs) generally perceived moderate benefits (Mean score (M) = 5.67) from information technology (IT) in healthcare. However, they slightly agreed that barriers like insufficient computers (M = 5.11), frequent system downtime (M = 5.09), low system performance (M = 5.04), and inadequate staff training (M = 4.88) hindered IT utilization. Respondents slightly agreed that training (M = 5.56), technical support (M = 5.46), and changes in work procedures (M = 5.10) motivated their IT use. Bivariate regression analysis revealed significant influences of education, working experience, healthcare profession, and IT training on attitudes towards IT utilization in healthcare delivery (BoIT, BITU, and MoITU). Additionally, the age of healthcare providers, education, and working experience significantly influenced BITU. Ultimately, age, education, working experience, healthcare profession, and IT training significantly influenced MoITU in healthcare delivery.

Conclusions

Healthcare professionals acknowledge moderate benefits of IT in healthcare but encounter barriers like inadequate resources and training. Motives for IT use include staff training and support. Bivariate regression analysis shows education, working experience, profession, and IT training significantly influence attitudes towards IT adoption. Targeted interventions and policies can enhance IT utilization in the Cape Coast Metropolis, Ghana.

Identification of the reporter gene combination that shows high contrast for cellular level MRI

by Naoya Hayashi, Junichi Hata, Tetsu Yoshida, Daisuke Yoshimaru, Yawara Haga, Hinako Oshiro, Ayano Oku, Noriyuki Kishi, Takako Shirakawa, Hideyuki Okano

Currently, we can label the certain cells by transducing specific genes, called reporter genes, and distinguish them from other cells. For example, fluorescent protein such as green fluorescence protein (GFP) is commonly used for cell labeling. However, fluorescent protein is difficult to observe in living animals. We can observe the reporter signals of the luciferin-luciferase system from the outside of living animals using in vivo imaging systems, although the resolution of this system is low. Therefore, in this study, we examined the reporter genes, which allowed the MRI-mediated observation of labeled cells in living animals. As a preliminary stage of animal study, we transduced some groups of plasmids that coded the protein that could take and store metal ions to the cell culture, added metal ions solutions, and measured their T1 or T2 relaxation values. Finally, we specified the best reporter gene combination for MRI, which was the combination of transferrin receptor, DMT1, and Ferritin-M6A for T1WI, and Ferritin-M6A for T2WI.

Assessing the basic knowledge and awareness of dengue fever prevention among migrant workers in Klang Valley, Malaysia

by Maryam N. Chaudhary, Voon-Ching Lim, Erwin Martinez Faller, Pramod Regmi, Nirmal Aryal, Siti Nursheena Mohd Zain, Adzzie Shazleen Azman, Norhidayu Sahimin

Background

Globally, 390 million dengue virus infections occur per year. In Malaysia, migrant workers are particularly vulnerable to dengue fever (DF) due to mosquito breeding sites exposure and poor health literacy. Therefore, this study aimed to (i) assess the current DF knowledge, attitudes and practices (KAP), and (ii) identify strategies to promote DF awareness, among migrant workers in Klang Valley.

Method

A survey was conducted with 403 Nepali, Filipino and Indonesian migrant workers through phone interviews and online self-administered questionnaires. Piecewise structural equation modelling was applied to identify predictor variables for DF KAP.

Results

Most respondents were male, working in the services industry, had completed high school, aged between 30–39 years and with less than ten years work experience in Malaysia. Overall, respondents’ knowledge was positively correlated with attitude but negatively with practices. Older respondents, who had completed higher education, obtained higher knowledge scores. Similarly, those with working experience of >20 years in Malaysia obtained higher attitude scores. Respondents with a previous history of DF strongly considered the removal of mosquito breeding sites as their own responsibility, hence tended to frequently practise DF preventive measures. Respondents’ knowledge was also positively correlated to their understanding of DF information sourced from social media platforms.

Conclusion

These findings highlighted: (i) the need for targeted DF educational intervention among younger and newly arrived workers with lower levels of education and (ii) maximising the usage of social media platforms to improve DF public awareness.

Validation of a web-based self-administered test for cognitive assessment in a Swedish geriatric setting

by Einar Rystedt, Jakob Morén, Johan Lindbäck, Vitor Tedim Cruz, Martin Ingelsson, Lena Kilander, Nuno Lunet, Joana Pais, Luis Ruano, Gabriel Westman

Computerized cognitive tests have the potential to cost-effectively detect and monitor cognitive impairments and thereby facilitate treatment for these conditions. However, relatively few of these tests have been validated in a variety of populations. Brain on Track, a self-administered web-based test, has previously been shown to have a good ability to differentiate between healthy individuals and patients with cognitive impairment in Portuguese populations. The objective of this study was to validate the differential ability and evaluate the usability of Brain on Track in a Swedish memory clinic setting. Brain on Track was administered to 30 patients with mild cognitive impairment/mild dementia and 30 healthy controls, all scheduled to perform the test from home after one week and after three months. To evaluate the usability, the patient group was interviewed after completion of the testing phase. Patients scored lower than healthy controls at both the first (median score 42.4 vs 54.1, p

Understanding spatiotemporal patterns of COVID-19 incidence in Portugal: A functional data analysis from August 2020 to March 2022

by Manuel Ribeiro, Leonardo Azevedo, André Peralta Santos, Pedro Pinto Leite, Maria João Pereira

During the SARS-CoV-2 pandemic, governments and public health authorities collected massive amounts of data on daily confirmed positive cases and incidence rates. These data sets provide relevant information to develop a scientific understanding of the pandemic’s spatiotemporal dynamics. At the same time, there is a lack of comprehensive approaches to describe and classify patterns underlying the dynamics of COVID-19 incidence across regions over time. This seriously constrains the potential benefits for public health authorities to understand spatiotemporal patterns of disease incidence that would allow for better risk communication strategies and improved assessment of mitigation policies efficacy. Within this context, we propose an exploratory statistical tool that combines functional data analysis with unsupervised learning algorithms to extract meaningful information about the main spatiotemporal patterns underlying COVID-19 incidence on mainland Portugal. We focus on the timeframe spanning from August 2020 to March 2022, considering data at the municipality level. First, we describe the temporal evolution of confirmed daily COVID-19 cases by municipality as a function of time, and outline the main temporal patterns of variability using a functional principal component analysis. Then, municipalities are classified according to their spatiotemporal similarities through hierarchical clustering adapted to spatially correlated functional data. Our findings reveal disparities in disease dynamics between northern and coastal municipalities versus those in the southern and hinterland. We also distinguish effects occurring during the 2020–2021 period from those in the 2021–2022 autumn-winter seasons. The results provide proof-of-concept that the proposed approach can be used to detect the main spatiotemporal patterns of disease incidence. The novel approach expands and enhances existing exploratory tools for spatiotemporal analysis of public health data.

Pharmacogenomics of poor drug metabolism in greyhounds: Canine P450 oxidoreductase genetic variation, breed heterogeneity, and functional characterization

by Stephanie E. Martinez, Amit V. Pandey, Tania E. Perez Jimenez, Zhaohui Zhu, Michael H. Court

Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds. However, CYP2B11 gene variants associated with decreased CYP2B11 expression do not fully explain reduced CYP2B11 activity in this breed. P450 oxidoreductase (POR) is an essential redox partner for all CYPs. POR protein variants can enhance or repress CYP enzyme function in a CYP isoform and substrate dependent manner. The study objectives were to identify POR protein variants in greyhounds and determine their effect on coexpressed CYP2B11 and CYP2D15 enzyme function. Gene sequencing identified two missense variants (Glu315Gln and Asp570Glu) forming four alleles, POR-H1 (reference), POR-H2 (570Glu), POR-H3 (315Gln, 570Glu) and POR-H4 (315Gln). Out of 68 dog breeds surveyed, POR-H2 was widely distributed across multiple breeds, while POR-H3 was largely restricted to greyhounds and Scottish deerhounds (35% allele frequencies), and POR-H4 was rare. Three-dimensional protein structure modelling indicated significant effects of Glu315Gln (but not Asp570Glu) on protein flexibility through loss of a salt bridge between Glu315 and Arg519. Recombinant POR-H1 (reference) and each POR variant (H2-H4) were expressed alone or with CYP2B11 or CYP2D15 in insect cells. No substantial effects on POR protein expression or enzyme activity (cytochrome c reduction) were observed for any POR variant (versus POR-H1) when expressed alone or with CYP2B11 or CYP2D15. Furthermore, there were no effects on CYP2B11 or CYP2D15 protein expression, or on CYP2D15 enzyme kinetics by any POR variant (versus POR-H1). However, Vmax values for 7-benzyloxyresorufin, propofol and bupropion oxidation by CYP2B11 were significantly reduced by coexpression with POR-H3 (by 34–37%) and POR-H4 (by 65–72%) compared with POR-H1. Km values were unaffected. Our results indicate that the Glu315Gln mutation (common to POR-H3 and POR-H4) reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings.

Telemedicine models of care: A retrospective review of telehealth in a Melbourne outpatient chronic wound service in 2021

Abstract

To review the application of telehealth guidelines developed by Bondini et al for clinicians to determine patient suitability for telehealth in an outpatient Chronic Wound Service, including the proportion of patients suitable for telehealth, type and mode of telehealth encounters. Retrospective, random convenience sample of patients attending the Chronic Wound Service in 2021. Fifty-six patients were included, most with leg/foot wounds (93%), median age 74 [54–84], 64% male. Four patients at admission and 19 patients at review met criteria for telehealth. Six percent of encounters were telehealth; phone-only (82%), unscheduled nursing reviews (77%) in patients with healing wounds. Thirty patients (54%) received at least one telehealth encounter. Telehealth occurred 35.6 days later in the admission than face-to-face encounters (p < 0.05, 95% CI 14.9–56.3). There was a significant relationship between patients receiving telehealth and meeting telehealth suitability criteria on reviews (X 2 (1) = 19.6*, p < 0.001). Eighteen percent of patients required wound-related hospitalisation during their outpatient admission. Telehealth guidelines identified patients suitable for telehealth, although the proportion of patients was small. Telehealth was mostly utilised for nurse-led telephone calls in patients with improving wounds. Future research into use of telephone review for clinical standards of wound care is warranted.

Factors associated with pressure ulcer and dehydration in long-term care settings in Ontario, Canada

by Mary Crea-Arsenio, Andrea Baumann, Valentina Antonipillai, Noori Akhtar-Danesh

Pressure ulcers and dehydration are common conditions among residents of long-term care facilities that result in negative health effects. They have been associated with signs of neglect and increased 30-day mortality among LTC residents. However, they are both preventable and with proper care can be effectively managed and treated. We conducted a retrospective cohort study to examine factors associated with pressure ulcers and dehydration among long-term care residents in the province of Ontario, Canada. Results indicated that close to one-fifth of residents were dehydrated (17.3%) or had a pressure ulcer (18.9%) during the study period. Advanced age was significantly associated with the presence of pressure ulcers and dehydration for both men and women. However, men were more likely to present with a pressure ulcer while women were more likely to exhibit symptoms of dehydration. Study findings also demonstrate the presence of both conditions being higher in municipal and not-for-profit homes compared to for-profit homes. The significant differences observed in relation to home ownership which require further investigation to identify the most relevant factors in explaining these differences. Overall, pressure ulcers and dehydration are preventable conditions that warrant attention from policymakers to ensure quality of care and resident safety are prioritized.

Non-invasive cumulus cell analysis can be applied for oocyte ranking and is useful for countries with legal restrictions on embryo generation or freezing

by Tom Adriaenssens, Inge Van Vaerenbergh, Lisbet Van Landuyt, Greta Verheyen, Michaël De Brucker, Michel Camus, Peter Platteau, Michel De Vos, Maria Reis, Elien Van Hecke, André Rosenthal, Johan Smitz

Research question

Can a strategy for scoring oocyte quality, based on cumulus cell (CC) gene expression, prioritize oocytes with the highest implantation potential, while limiting the number of embryos to be processed in culture and the number of supernumerary embryos to be vitrified?

Design

An interventional, blinded, prospective cohort study was retrospectively analyzed. In the original study, patients underwent a fresh Day3 single embryo transfer with embryos ranked based on morphology and CC gene expression (Aurora Test). The additional ranking of the embryos with the Aurora Test resulted in significant higher clinical pregnancy and live birth rates. Now it is investigated if the Aurora Test ranking could be applied to select oocytes. The effect of an Aurora Test based restriction to 2 and 3 2PN or MII oocytes on clinical pregnancy and other outcomes, was analyzed in two subsets of patients with all 2PN (n = 83) or all MII oocytes (n = 45) ranked.

Results

Considering only the top three ranked 2PN oocytes, 95% of the patients would have received a fresh SET on Day3 resulting in 65% clinical pregnancies. This was not different from the pregnancy rate obtained in a strategy using all oocytes but significantly reduced the need for vitrification of supernumerary embryos by 3-fold. Considering only top-ranked MII oocytes gave similar results.

Conclusions

In countries with legal restrictions on freezing of embryos, gene expression of CC can be used for the selective processing of oocytes and would thus decrease the twin pregnancy rate and workload, especially for embryo morphology scoring and transfers as the handling and processing of lower competence oocytes is prevented, while improving the ART outcome.

Ultrasound tomography enhancement by signal feature extraction with modular machine learning method

by Bartłomiej Baran, Dariusz Majerek, Piotr Szyszka, Dariusz Wójcik, Tomasz Rymarczyk

Robust and reliable diagnostic methods are desired in various types of industries. This article presents a novel approach to object detection in industrial or general ultrasound tomography. The key idea is to analyze the time-dependent ultrasonic signal recorded by three independent transducers of an experimental system. It focuses on finding common or related characteristics of these signals using custom-designed deep neural network models. In principle, models use convolution layers to extract common features of signals, which are passed to dense layers responsible for predicting the number of objects or their locations and sizes. Predicting the number and properties of objects are characterized by a high value of the coefficient of determination R2 = 99.8% and R2 = 98.4%, respectively. The proposed solution can result in a reliable and low-cost method of object detection for various industry sectors.

Supporting regional pandemic management by enabling self-service reporting—A case report

by Richard Gebler, Martin Lehmann, Maik Löwe, Mirko Gruhl, Markus Wolfien, Miriam Goldammer, Franziska Bathelt, Jens Karschau, Andreas Hasselberg, Veronika Bierbaum, Toni Lange, Katja Polotzek, Hanns-Christoph Held, Michael Albrecht, Jochen Schmitt, Martin Sedlmayr

Background

The COVID-19 pandemic revealed a need for better collaboration among research, care, and management in Germany as well as globally. Initially, there was a high demand for broad data collection across Germany, but as the pandemic evolved, localized data became increasingly necessary. Customized dashboards and tools were rapidly developed to provide timely and accurate information. In Saxony, the DISPENSE project was created to predict short-term hospital bed capacity demands, and while it was successful, continuous adjustments and the initial monolithic system architecture of the application made it difficult to customize and scale.

Methods

To analyze the current state of the DISPENSE tool, we conducted an in-depth analysis of the data processing steps and identified data flows underlying users’ metrics and dashboards. We also conducted a workshop to understand the different views and constraints of specific user groups, and brought together and clustered the information according to content-related service areas to determine functionality-related service groups. Based on this analysis, we developed a concept for the system architecture, modularized the main services by assigning specialized applications and integrated them into the existing system, allowing for self-service reporting and evaluation of the expert groups’ needs.

Results

We analyzed the applications’ dataflow and identified specific user groups. The functionalities of the monolithic application were divided into specific service groups for data processing, data storage, predictions, content visualization, and user management. After composition and implementation, we evaluated the new system architecture against the initial requirements by enabling self-service reporting to the users.

Discussion

By modularizing the monolithic application and creating a more flexible system, the challenges of rapidly changing requirements, growing need for information, and high administrative efforts were addressed.

Conclusion

We demonstrated an improved adaptation towards the needs of various user groups, increased efficiency, and reduced burden on administrators, while also enabling self-service functionalities and specialization of single applications on individual service groups.

Effect of vitamin D on clinical outcomes in patients with thermal injury

Abstract

Evaluating complications and mortality risks in burn patients is crucial for effective treatment planning and improving survival rates. This study investigated the relationship between the serum vitamin D level and the clinical outcomes of adult burns patients. This was a prospective cohort of adult patients hospitalized due to thermal burns at a burn centre in the north of Iran. Based on the level of 25 hydroxyvitamin D measured upon admission, patients were divided into two groups of patients with sufficient 25 hydroxyvitamin D level and insufficient 25 hydroxyvitamin D level. Descriptive statistics were used for baseline demographics. Univariate analysis was conducted using Mann–Whitney U, Chi-square, independent samples, and Fisher's exact tests. A multivariate logistic regression was performed to adjust for the effects of confounding variables. Statistical analyses were conducted using SPSS 28.0 software. A total of 220 patients were included in the study. The average total body surface area burned was 30.52 ± 9.34. Patients with insufficient vitamin D levels had longer hospital stays (12.53 vs. 11.45) and longer stays in the intensive care unit (ICU) (3.32 vs. 2.40) than those with appropriate vitamin D levels. Participants with insufficient vitamin D levels exhibited a numerically higher incidence of infections than those with adequate levels (p < 0.05). The multivariate regression found that vitamin D deficiency levels were associated with increased infection rates and prolonged hospital stay. This study suggests that vitamin D deficiency is a significant risk factor for adverse clinical outcomes in burn patients. Further research is needed to confirm these associations and to explore potential interventions to optimize vitamin D status in this patient population.

Real-world prescription of anti-COVID-19 drugs in hospitalized patients with COVID-19 in Japan

by Haruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama

Objective

Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan.

Design

The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan.

Participants

Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021.

Exposures

The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine.

Results

We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period.

Conclusions and relevance

This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.

Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1

by Dimitrios G. Anastasakis, Daniel Benhalevy, Nicolas Çuburu, Nihal Altan-Bonnet, Markus Hafner

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.

Implementation of antimicrobial stewardship programs: A study of prescribers’ perspective of facilitators and barriers

by Emelda E. Chukwu, Dennis Abuh, Ifeoma E. Idigbe, Kazeem A. Osuolale, Vivian Chuka-Ebene, Oluwatoyin Awoderu, Rosemary A. Audu, Folasade T. Ogunsola

Background

Despite promising signs of the benefits associated with Antimicrobial Stewardship Programs (ASPs), there remains limited knowledge on how to implement ASPs in peculiar settings for a more elaborate impact. This study explored prescriber experiences and perceptions of the usefulness, and feasibility of strategies employed for the implementation of antimicrobial stewardship (AMS) interventions as well as challenges encountered.

Methods

This is a cross-sectional mixed-method survey of prescribers’ perspective of the facilitators and barriers of implementing ASP. The quantitative approach comprised of a semi-structured questionnaire and data collected were analyzed using SPSS version 26 while the qualitative approach used focus group discussions followed by content analysis.

Results

Out of the thirty people that participated in the workshop, twenty-five completed the questionnaires which were analyzed. The respondents included 15 (60.0%) medical doctors and 10 (40.0%) pharmacists. The mean age of the respondents was 36.39±7.23 years with mean year of practice of 9.48±6.01 years. Majority of them (84.0%) were in a position to provide input on the implementation of AMS in their facilities, although their managements had the final decision. The pharmacists (100%) were more likely to agree that antibiotic resistance was a problem for their practice than the medical doctors (78.6%) while equal number (80.0%) of respondents (pharmacists and medical doctors) believed that inappropriate prescribing was a problem. Having a specialized and dedicated team with effective monitoring was recognized as crucial for effective ASP while inadequate personnel was identified as a major barrier. We identified stakeholder’s engagement, policies and regulation, as well as education as themes for improving AMS in the country.

Conclusion

The results gave insight into the prescribers’ perspective on the facilitators and barriers to antimicrobial stewardship; challenges and possible solutions to implementing ASPs in health facilities in Lagos State. We further identified pertinent contextual factors that need to be addressed when developing ASPs in healthcare facilities in a resource-poor setting.

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

by Sergei A. Fedotov, Maria S. Khrabrova, Elena S. Vashukova, Andrey S. Glotov, Anastasia O. Anpilova, Vladimir A. Dobronravov, Maria E. Velizhanina, Aleksandr A. Rubel

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30–100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

Exploring knowledge, perceptions, and practices of antimicrobials, and their resistance among medicine dispensers and community members in Kavrepalanchok District of Nepal

by Sabina Marasini, Sudim Sharma, Anjali Joshi, Surakshya Kunwar, Roshan Kumar Mahato, Archana Shrestha, Biraj Karmacharya

Background

Inappropriate use of antimicrobials is a global public health issue, particularly in developing countries, including Nepal, where over-the-counter sales and self-medication of antimicrobials are common.

Objectives

To explore knowledge, perceptions, and practices of antimicrobials and their resistance among medicine dispensers and community members in Nepal.

Methods

The study was conducted in three rural and five urban municipalities of the Kavrepalanchok district from May 2021 to August 2021. Data were collected using two qualitative approaches: In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). Data were analyzed using thematic analysis that combined deductive and inductive approaches to identify codes under pre-specified themes.

Results

A total of 16 In-depth interviews with medicine dispensers and 3 focus group discussions with community members were conducted. Knowledge regarding antimicrobial resistance varied among dispensers. Those with a prior educational background in pharmacy often had good knowledge about the causes and consequences of antimicrobial resistance. Meanwhile, consumers were less aware of antimicrobial resistance. Community members perceived antimicrobials as effective medicines but not long-term solution for treating diseases. They reported that dispensing without a prescription was common and that both consumers and dispensers were responsible for the inappropriate use of antimicrobials. On the contrary, several dispensers said that self-medication was common among the consumers, especially among more educated groups. The medicine dispensers and consumers expressed concerns about the weak enforcement of policies regarding pharmacy drug use and dispensing practices.

Conclusion

Promoting and strengthening the appropriate use of antimicrobials among medicine dispensers and community members is crucial. Bold policies and collective implementation of regulations could help combat antimicrobial resistance.

Evaluating deep learning-based melanoma classification using immunohistochemistry and routine histology: A three center study

by Christoph Wies, Lucas Schneider, Sarah Haggenmüller, Tabea-Clara Bucher, Sarah Hobelsberger, Markus V. Heppt, Gerardo Ferrara, Eva I. Krieghoff-Henning, Titus J. Brinker

Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine.
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