Updated Report Research Articles

Evidence synthesis for COVID-19 interventions: update reports from Argentina's National Commission for Health Technology AssessmentSíntese de evidências para intervenções em COVID-19: relatórios de atualização da Comissão Nacional de Avaliação de Tecnologias em Saúde da Argentina

This report presents the work done on the design, publication, and impact of updates on evidence-based COVID-19 interventions, in order to support decision-making with updated evidence syntheses based on living systematic reviews of therapeutic interventions. To this end, a specific working group was created within the National Commission for Health Technology Assessment (CONETEC) of the Ministry of Health of Argentina, in collaboration with the Pan American Health Organization (PAHO). A methodology was designed to develop and publish assessment documents aimed at supporting decision-making. These update reports were based on the exploration of three areas: health effects, feasibility of implementation, and evidence-based recommendations. A color-coded system was used to present the conclusions according to the balance between their positive and negative effects in different clinical scenarios, in order to improve their interpretation and implementation. In 2021, 16 evidence synthesis reports were published (13 original reports and three full updates). These were downloaded many times from the CONETEC website and the Regional Database of Health Technology Assessment Reports of the Americas (BRISA), highlighting the need for robust, up-to-date, reliable evidence summaries adapted for implementation in the country's health system. Other challenges include constant updating of information, appropriate dissemination, and sustained rigorous preparation of the reports.

Update report on Virological and mortality distribution and implication of Covid -19 pandemic across the globe from 28th January to 3rd February, 2022.

Background and Objective: Scientists and world leaders are still trying to understand COVID-19 and its potential global consequences. While there have been some successes, there are still many that remain unknown. This study provides an update report on the virological and immunological distribution and implications of the COVID-19 pandemic around the world from January 28th to February 3rd, 2022..Material and Method: The United Nations geoscheme was used to obtain data from 196 countries and regions around the world. The results were compiled and compared to the values obtained for the United States.Results: When available data was compared to that of the United States, the American continent had a higher mortality comparison factor than infection cases, whereas the European continents had a higher infectious comparison value than mortality value. With the exception of South Africa and Botswana, the African continents appear unconcerned about the value of mortality and infectivity.Conclusion: The new wave and virus variant have caused a resurgence in its global impact. There is a need to understand how Africa has survived all variants of the virus despite having few medical resources.

Using pharmacy surveillance information systems to monitor the dispensing practice of under-controlled drugs: A qualitative study on necessities, requirements, and implementation challenges

The food and drug administration (FDA) usually monitors drug dispensing practices to manage their resources. Despite advances in information technology, traditional paper-based processes are used for this purpose in several low and middle income countries. This study aimed to determine the necessities, requirements, and implementation challenges of using pharmacy surveillance information systems (PSISs) to monitor the dispensing practice of under-controlled drugs and substances. This qualitative study was conducted in 2021. The population of the study was 16 FDA managers and pharmacy owners and pharmacy information systems (PIS) users in Iran. First, data collection was performed through open-ended, semi-structured interviews. Then, a focus group including experts in pharmacology, health information management, medical informatics, and information technology reviewed and confirmed the necessities, requirements, users' information needs, and implementation challenges of the PSIS. The results of the study showed that improving safety, conducting utilization management, reducing doctor shopping, and supporting patients were the most important reasons to monitor the dispensing practice of under-controlled drugs. The participants believed that the electronic monitoring of the dispensing of under-controlled drugs is essential and can increase the accuracy, timeliness, and ease of performing relevant processes. Based on the participants’ opinions, registering the data related to patients, prescribers, prescriptions, and pharmacies is necessary. The system should have functionalities to prevent illegal events and generate timely and updated reports. Resistance of stakeholders and shortage of infrastructure were identified as the main challenges for the implementation. Improving safety and supporting patients necessitate monitoring the dispensing practice of under-controlled drugs. To monitor this important practice, using a PSIS is necessary and it can support and facilitate the related processes.

CrowdSPaFE: A Crowd-Sourced Multimodal Recommendation System for Urban Route Safety

In the age of information technology, location-based services such as Google Maps, Bing Maps, and Apple Maps have become popular for navigation and traffic information. These services usually consider the shortest path, traffic information, nearby places, and multi-modal alternative route suggestions based on a user’s constraints. Nevertheless, these services do not always provide the best choice in terms of "user safety". Recently, some research and mobile applications have considered safety issues. Notably, none of these are capable of adapting to dynamic, conflicting safety features and real-time user feedback. Recently, a population-based algorithm called "SPaFE" has been introduced, which deals with crowd-sourced data along with historic data. This population-based approach, however, does not give more weight to recent feedback than to earlier feedback and does not consider updated crime reports. Furthermore, this approach does not consider distance and performs poorly in the area with insignificant or zero feedback. Considering the above background, we have introduced the population based algorithm "CrowdSPaFE" to adapt with dynamic crime reports, latest feedback, navigation in areas with insignificant feedback, and a trade-off between distance and safety factors. Finally, our empirical results of the "CrowdSPaFE" algorithm depict that it significantly outperforms the state of the art.

Modern Approaches to <i>H. pylori</i> Eradication Therapy in Adults (Literature Review and Resolution of Experts Council)

Aim: to analyze current approaches to H. pylori eradication therapy in adults and present the materials of Experts Council held on December 9, 2022 in Moscow.General statements. H. pylori infection is the main etiological factor of gastritis, peptic ulcer, and gastric cancer. Eradication of H. pylori is recognized as a necessary measure to reduce the incidence of these diseases. The approaches to selecting an eradication regimen should be optimized to take into account epidemiological trends and achieve better treatment outcomes. The updated Maastricht VI Consensus Report presents the means to overcome the difficulties in selecting an approach to the treatment of H. pylori infection. However, eradication therapy remains challenging due to adverse events (primarily antibiotic-associated diarrhea), poor treatment tolerance and patient compliance. Eradication therapy can be optimized by supplementing treatment regimens with strain-specific probiotics that reduce adverse events, improve patient compliance and eradication rates, such as Saccharomyces boulardii CNCM I-745 strain with established efficacy.Conclusion. The inclusion of certain probiotics in eradication regimens improves treatment tolerance, reduces the risk of adverse events, improves patient compliance and eradication rates.

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update

PurposeThis updated report on image guided radiation therapy (IGRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology addressing patient safety. Since the first white papers were published, IGRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The use of IGRT has now extended beyond high-precision treatments, such as stereotactic radiosurgery and stereotactic body radiation therapy, and into routine clinical practice for many treatment techniques and anatomic sites. Therefore, quality and patient safety considerations for these techniques remain an important area of focus. Methods and MaterialsThe American Society for Radiation Oncology convened an interdisciplinary task force to assess the original IGRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology, and task force members indicated their level of agreement based on a 5-point Likert scale from “strongly agree” to “strongly disagree.” A prespecified threshold of ≥75% of raters who selected “strongly agree” or “agree” indicated consensus. SummaryThis IGRT white paper builds on the previous version and uses other guidance documents to primarily focus on processes related to quality and safety. IGRT requires an interdisciplinary team-based approach, staffed by appropriately trained specialists, as well as significant personnel resources, specialized technology, and implementation time. A thorough feasibility analysis of resources is required to achieve the clinical and technical goals and should be discussed with all personnel before undertaking new imaging techniques. A comprehensive quality-assurance program must be developed, using established guidance, to ensure IGRT is performed in a safe and effective manner. As IGRT technologies continue to improve or emerge, existing practice guidelines should be reviewed or updated regularly according to the latest American Association of Physicists in Medicine Task Group reports or guidelines. Patient safety in the application of IGRT is everyone's responsibility, and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to ensure the highest levels of safety.

COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19.

The number of reported cases with coronavirus disease 2019 (COVID-19) has exceeded 620 million worldwide, still having a profound impact on people's health and daily lives since its occurrence and outbreak in December 2019. From the early phase of the COVID-19 pandemic, there has been a concern that the rapid spread of this communicable disease can negatively influence non-communicable diseases. Accumulating data indicate that the restriction on the access to medical care, psychological distress, and life-style changes triggered by the pandemic have indeed affected blood pressure control in hypertensive patients. Since our previous report in 2020 that summarized the findings of the literature related to COVID-19 and hypertension, there has been a considerable progress in our understanding of the association between these two disorders; nonetheless, there are remaining challenges and emerging questions in the field. In this article, we aim to summarize the latest information on the impact of the pandemic on blood pressure control, the use of the renin-angiotensin system inhibitors in patients with COVID-19, and the blood pressure changes as one of the possible post-acute sequelae of COVID-19 (also known as long COVID). We also summarize the evidence of telemedicine and COVID-19 vaccination in hypertensive subjects, based on data available as of June 2022.

Pro: Does Every Anesthesiologist Need to Learn Point-of-Care Ultrasound?

THE APPLICATIONS OF ULTRASOUND for the anesthesiologist are diverse and expanding rapidly. Although national society guidelines governing the appropriate use of ultrasound in anesthesiology have been available only for transesophageal echocardiography (TEE) and vascular access imaging, clinical guidance has more recently been published describing the use of focused cardiac ultrasound in multiple clinical contexts. 1 Troianos CA Hartman GS Glas KE et al. Guidelines for performing ultrasound guided vascular cannulation: Recommendations of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists. J Am Soc Echocardiogr. 2011; 24: 1291-1318 Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar , 2 American Society of Anesthesiologists and Society of Cardiovascular Anesthesiologists Task Force on Transesophageal EchocardiographyPractice guidelines for perioperative transesophageal echocardiography. An updated report by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists Task Force on Transesophageal Echocardiography. Anesthesiology. 2010; 112: 1084-1096 Crossref PubMed Scopus (391) Google Scholar , 3 Spencer KT Kimura BJ Korcarz CE et al. Focused cardiac ultrasound: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2013; 26: 567-581 Abstract Full Text Full Text PDF PubMed Scopus (398) Google Scholar , 4 Via G Hussain A Wells M et al. International evidence-based recommendations for focused cardiac ultrasound. J Am Soc Echocardiogr. 2014; 27 (683.e1-683.e33) Abstract Full Text Full Text PDF PubMed Scopus (368) Google Scholar Additionally, numerous point-of-care ultrasound (POCUS) protocols now exist to guide the examination of nearly every organ system and area, including cardiac, pulmonary and/or pleural, abdominal, genitourinary, ocular, and airway. 4 Via G Hussain A Wells M et al. International evidence-based recommendations for focused cardiac ultrasound. J Am Soc Echocardiogr. 2014; 27 (683.e1-683.e33) Abstract Full Text Full Text PDF PubMed Scopus (368) Google Scholar , 5 Haskins SC Bronshteyn Y Perlas A et al. American Society of Regional Anesthesia and Pain Medicine expert panel recommendations on point-of-care ultrasound education and training for regional anesthesiologists and pain physicians-part I: Clinical indications. Reg Anesth Pain Med. 2021; 46: 1031-1047 Crossref PubMed Scopus (15) Google Scholar , 6 Haskins SC Bronshteyn Y Perlas A et al. American Society of Regional Anesthesia and Pain Medicine expert panel recommendations on point-of-care ultrasound education and training for regional anesthesiologists and pain physicians-part II: Recommendations. Reg Anesth Pain Med. 2021; 46: 1048-1060 Crossref PubMed Scopus (14) Google Scholar , 7 Holm JH Frederiksen CA Johl-Olsen P et al. Perioperative use of focus assessed transthoracic echocardiography (FATE). Anesth Analg. 2012; 115: 1029-1032 Crossref PubMed Scopus (71) Google Scholar , 8 Lichtenstein DA Mezière GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: The BLUE protocol. Chest. 2008; 134: 117-125 Abstract Full Text Full Text PDF PubMed Scopus (1146) Google Scholar , 9 Volpicelli G Elbarbary M Blaivas M et al. International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012; 38: 577-591 Crossref PubMed Scopus (1758) Google Scholar , 10 Scalea TM Rodriguez A Chiu WC et al. Focused Assessment with Sonography for Trauma (FAST): Results from an international consensus conference. J Trauma. 1999; 46: 466-472 Crossref PubMed Google Scholar , 11 Perlas A Van de Putte P Van Houwe P et al. I-AIM framework for point-of-care gastric ultrasound. Br J Anaesth. 2016; 116: 7-11 Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar

Long-Term Update of NRG/RTOG 0522: A Randomized Phase 3 Trial of Concurrent Radiation and Cisplatin With or Without Cetuximab in Locoregionally Advanced Head and Neck Cancer

The combination of cisplatin and radiation or cetuximab and radiation improves overall survival of patients with locoregionally advanced head and neck carcinoma. NRG Oncology conducted a phase 3 trial to test the hypothesis that adding cetuximab to radiation and cisplatin would improve progression-free survival (PFS). Eligible patients with American Joint Committee on Cancer sixth edition stage T2 N2a-3 M0 or T3-4 N0-3 M0 were accrued from November 2005 to March 2009 and randomized to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Outcomes were correlated with patient and tumor features. Late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Of 891 analyzed patients, 452 with a median follow-up of 10.1 years were alive at analysis. The addition of cetuximab did not improve PFS (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89-1.26; P=.74), with 10-year estimates of 43.6% (95% CI, 38.8- 48.4) for arm A and 40.2% (95% CI, 35.4-45.0) for arm B. Cetuximab did not reduce locoregional failure (HR, 1.21; 95% CI, 0.95-1.53; P=.94) or distant metastasis (HR, 0.79; 95% CI, 0.54-1.14; P=.10) or improve overall survival (HR, 0.97; 95% CI, 0.80-1.16; P=.36). Cetuximab did not appear to improve PFS in either p16-positive oropharynx (HR, 1.30; 95% CI, 0.87-1.93) or p16-negative oropharynx or nonoropharyngeal primary (HR, 0.94; 95% CI, 0.73-1.21). Grade 3 to 4 late toxicity rates were 57.4% in arm A and 61.3% in arm B (P=.26). With a median follow-up of more than 10 years, this updated report confirms the addition of cetuximab to radiation therapy and cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status.

Shark incidents in California 1950-2021; frequency and trends

Many reports have categorized the frequency, circumstances, and causes for interactions between sharks and humans, often using the behaviorally inaccurate term “attack.” The California Department of Fish and Wildlife (Department) instead uses the term “incident,” defined as interactions where a shark touches a person, their board, or kayak, without provocation and with or without causing injury. We created a comprehensive database of California shark incidents by reviewing, verifying, and updating past records, and examined the frequency of confirmed incidents, updated reports with new information, and examined similarities and differences in incident circumstances. Two hundred and one incidents were verified in California waters between 1950 and 2021, with 107 causing injury and 15 resulting in fatalities. The vast majority (178) involved White Sharks (Carcharodon carcharias). Contrary to past reports of White Shark incidents being concentrated in a portion of northern California, incidents have occurred statewide, with some of the highest numbers in Southern California. While total reported incidents are increasing, the annual number of incidents resulting in injuries or fatalities remains low. Frequency of incidents was not found to be greater around the full moon, dawn, or dusk but was greater during summer and fall months, as expected.

Quality and Safety Considerations in Intensity Modulated Radiation Therapy: An ASTRO Safety White Paper Update

This updated report on intensity modulated radiation therapy (IMRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology (ASTRO) addressing patient safety. Since the first white papers were published, IMRT went from widespread use to now being the main delivery technique for many treatment sites. IMRT enables higher radiation doses to be delivered to more precise targets while minimizing the dose to uninvolved normal tissue. Due to the associated complexity, IMRT requires additional planning and safety checks before treatment begins and, therefore, quality and safety considerations for this technique remain important areas of focus. ASTRO convened an interdisciplinary task force to assess the original IMRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology, and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who select "strongly agree" or "agree" indicated consensus. This IMRT white paper primarily focuses on quality and safety processes in planning and delivery. Building on the prior version, this consensus paper incorporates revised and new guidance documents and technology updates. IMRT requires an interdisciplinary team-based approach, staffed by appropriately trained individuals as well as significant personnel resources, specialized technology, and implementation time. A comprehensive quality assurance program must be developed, using established guidance, to ensure IMRT is performed in a safe and effective manner. Patient safety in the delivery of IMRT is everyone's responsibility, and professional organizations, regulators, vendors, and end-users must work together to ensure the highest levels of safety.

Analysis of sex steroids in human tears using LC-MS and GC-MS: Considerations and developments to improve method sensitivity and accuracy.

Sex steroids play a role in regulation of tear film function and may exert their action locally at the ocular surface. However, measurement of sex steroids in tears is difficult due to small-volume tear samples and very low concentrations of the hormones. This short communication highlights what has been achieved to date in the analysis of tear sex steroids using ultra-performance LC-MS (UPLC-MS) as previously published, and reports further and more recent investigations toward optimising mass spectrometry method sensitivity and accuracy. The published UPLC-MS method successfully measured progesterone, androsterone glucuronide and 5α-androstane-3α,17β-diol in pooled basal tears of postmenopausal women, and fourteen sex steroid standards in methanol. Limitations included sub-optimal limits of detection (LOD) and lower limits of quantification (LLOQ) for some analytes (particularly oestrogens), exclusion of sample matrix effects and no use of internal standards. This update reports on further experiments carried out to improve sensitivity and accuracy. Sample matrix effects, internal standard spiking, and derivatisation with dansyl chloride and oximes were investigated. Dansylation significantly improved the LOD and LLOQ of oestrogens and their metabolites, by a factor of 10 for oestradiol and a factor of 5 for oestrone, but sensitivity of this updated method is not sufficient however for analysis of these oestrogens in human tears. Using gas chromatography-mass spectrometry (GC-MS) as an alternative technique to LC-MS, improved sensitivity for derivatised oestradiol is reported. This work demonstrates the need to develop higher sensitivity methods and points researchers towards specific MS ionisation techniques for future analysis of sex steroids in tears, in order to progress current understanding of the role of sex steroids in tear function and dry eye.

The WW‐FINGERS‐SARS‐CoV‐2 initiative: a multinational survey to assess the effects of the COVID‐19 Pandemic on Lifestyle and Psychosocial factors relevant to Brain Health

AbstractBackgroundglobal population aging and forecasted trends of modifiable risk factors for dementia and Alzheimer’s disease (AD) make prevention of these conditions an urgent priority. The World‐Wide FINGERS (WW‐FINGERS) global network of multidomain trials for dementia risk reduction and prevention is at the forefront of efforts to find effective and sustainable solutions for diverse population. The COVID‐19 pandemic has caused changes in the mental and physical health of older adults, which can influence dementia risk and prevention opportunities.MethodsThe WW‐FINGERS‐SARS‐CoV‐2 survey was developed to assess direct and indirect effects of the COVID‐19 pandemic in older adults. The questionnaire measures changes in lifestyle factors (e.g., diet, physical activity), management of chronic noncommunicable diseases (e.g., diabetes, hypertension), and psychosocial factors ‐including depressive symptoms, sleep disorders, social isolation‐ that are relevant to cognition. Both a pen‐and‐paper and a digital version of the survey have been developed in several languages. The digital version is supported through REDCap (Research Electronic Data Capture), which is used also for harmonized data collection.Results30 countries are participating in the survey. As for January 2022, data have been collected from 20 countries, with 23000+ participants. Local adaptations and piloting were done to optimize implementation in clinical‐based and population‐based settings. Participants are in the at‐risk spectrum for dementia: from normal cognition to pre‐dementia cognitive symptoms. Timing of the survey implementation varies across populations, allowing to capture short, medium and long‐term effects of the pandemic and restrictions measures. Some countries have used the survey to recruit participants in multimodal prevention trials. An updated report of the survey status and main results will be presented.ConclusionThe WW‐FINGERS‐SARS‐CoV2 survey is a joint global action of the WW‐FINGERS network which can inform better care of older adults in the context of a pandemic. The survey is also a valuable tool for pre‐screening of participants for prevention trials, and results can inform adaptions to ensure successful recruitment and adherence in forthcoming multidomain trials for dementia prevention in older adults.

PP23 Lost In Translation? The Differences In The Use Of Real-World Evidence Across Key Markets

IntroductionHealth Technology Assessment (HTA) agencies have recognized the importance of real-world evidence (RWE) to inform access decision-making and different HTA agencies establish distinct requirements for their local jurisdictions. The objective of this study is to understand the differences of RWE included in HTA reports and HTA agencies’ perception of RWE.MethodsHTA reports from agencies in France, Germany, Spain, Italy, United Kingdom (UK), Canada, Australia and South Korea from January 2011 to November 2021, including original submissions, resubmissions, extensions of original indications and renewals were analyzed.ResultsAcross the eight countries, RWE has been used in nineteen percent of all HTA reports (N=2,960/15,561), with an exponential increase observed between 2019 and 2021. RWE on clinical effectiveness was mostly used in HTA submissions in the UK (twenty-two percent), with twenty-six percent perceived with full acceptance. In contrast, RWE on safety and epidemiology was reported widely in HTA reports in France and Germany (83% and 87%), respectively. Ninety-three percent of RWE received full acceptance in France, followed by forty-four percent in Germany. A mixed picture of the types of RWE included in HTA reports was observed in the other countries, with high variance of acceptance (between 5 to 37%).ConclusionsFrance, Germany, and the UK are the top three countries with a large proportion of HTA reports where RWE was mentioned. The type of RWE used is related to a large extent to the local evidence requirements. For example, RWE around epidemiology was included widely in Germany due to the needs of providing local data for budget impact analyses required by the Federal Joint Committee (G-BA); RWE on tolerability as reported in periodic safety update reports (PSURs) needs to be included in French HTA submissions. RWE on clinical effectiveness has been evaluated the most by the UK HTA bodies.

Development, validation and application of a gas chromatography method for the determination of dillapiole from Piper aduncum essential oil in skin permeation samples.

The essential oil extracted from the leaves of Piper aduncum has antifungal, insecticidal and antibacterial activity. Studies with its main compound, dillapiole (DIL) revealed antibacterial and anti-inflammatory potential. Despite all this bioactivity, there is no updated report on the development and validation of analytical and bioanalytical methodology to quantify DIL in skin samples. A selective, precise, accurate and adequate method for the determination of DIL in solutions, porcine ear skin samples and receptor fluid was developed and validated by headspace extraction-gas chromatography with flame ionization detection (HS-GC-FID). HS-GC-FID was applied to determine DIL in Franz cell permeation and retention studies using porcine ear skin samples. In the HS-GC-FID method, matrix-related interferences were not observed at the peak of the DIL retention time. The results showed a high recovery (>97%) after the extraction procedure, allowing the quantification of DIL in complex matrices. In vitro permeation/retention for DIL showed cumulative amounts permeated in the order: receptor fluid (21.98 ± 1.19 μg/cm2 ) > epidermis (15.40 ± 1.20 μg/cm2 ) > dermis (9.52 ± 1.13 μg/cm2 ). HS-GC-FID was successfully validated and the results point to DIL transdermal permeation and to the potential to develop pharmaceutical formulations for skin delivery to treat inflammation or infections.

Voltage-gated sodium channels in diabetic sensory neuropathy: Function, modulation, and therapeutic potential.

Voltage-gated sodium channels (Na V ) are the main contributors to action potential generation and essential players in establishing neuronal excitability. Na V channels have been widely studied in pain pathologies, including those that develop during diabetes. Diabetic sensory neuropathy (DSN) is one of the most common complications of the disease. DSN is the result of sensory nerve damage by the hyperglycemic state, resulting in a number of debilitating symptoms that have a significant negative impact in the quality of life of diabetic patients. Among those symptoms are tingling and numbness of hands and feet, as well as exacerbated pain responses to noxious and non-noxious stimuli. DSN is also a major contributor to the development of diabetic foot, which may lead to lower limb amputations in long-term diabetic patients. Unfortunately, current treatments fail to reverse or successfully manage DSN. In the current review we provide an updated report on Na V channels including structure/function and contribution to DSN. Furthermore, we summarize current research on the therapeutic potential of targeting Na V channels in pain pathologies, including DSN.

ClotChip Portable Blood Clotting Sensor


 Horizon Scan reports provide brief summaries of information regarding new and emerging health technologies; Health Technology Update reports typically focus on a single device or intervention. This Horizon Scan summarizes the available information regarding an emerging technology, ClotChip, for the identification of blood clotting defects.
 ClotChip is intended for use at the point of care and uses novel, low-cost technology to perform a rapid assessment of the blood's clotting ability.
 Early evidence has demonstrated the feasibility and utility of ClotChip, which could benefit patients with a variety of bleeding disorders and could potentially save time for health care professionals.

Using simulation to improve confidence in the escalation of patients with learning disabilities by nurses in the acute care setting

The National Early Warning Score (NEWS) is used to collate measurements of patients’ vital functions, identifying patients who require management to prevent deterioration [1]. Not following NEWS escalation protocols is linked to adverse events and may occur due to prioritising clinical judgement over scores and communication failures [2]. Patients with learning disabilities are even more at risk of avoidable adverse events in hospital, but education to improve the understanding of the needs of these patients may be a protection against this [3]. This research assessed the improved confidence of nurses in escalation following a simulation-based course focused on escalating an unwell patient with learning difficulties. The course started with an interactive talk on how to measure NEWS by a nurse educator. A simulation-based video we created of a mismanaged scenario involving a patient with learning disabilities was shown, followed by a discussion about handover using the SBAR structure. The simulation required the attendee accurately calculating a NEWS score of an actor connected to a monitor we could control and escalate to a doctor over the phone. This simulation was shown in real time to the other attendees, and the debriefing was facilitated by a doctor trained in debriefing. Pre- and post-course questionnaires were completed by attendees to assess their nursing experience, confidence in assessing NEWS, and escalation rated on a scale of 0 (very unconfident) to 5 (very confident). The course was run 6 times for a total of 26 nurses. The median length of nursing experience was 17 months (range 1–249months). More attendees were confident (defined as 4 or 5 out of 5 in the confidence scale) in assessing NEWS, escalating to the medical team, and using SBAR post-course (96%, 96%, and 93% respectively) compared to pre-course (68%, 57%, and 54% respectively), which can be seen in Confidence of the participating nurses before and after the course. This simulation-based course focusing on care of a patient with learning disabilities has improved confidence in assessing NEWS and escalation with a structured handover to the medical team. Further research should be focused on multidisciplinary simulation on escalation in the acute care setting, and how including cases involving learning disabilities improves outcomes in this at-risk group. 1. Royal College of Physicians. National Early Warning Score (NEWS) 2 Standardising the assessment of acute-illness severity in the NHS. Updated report of a working party. London: 2017. 2. Ede J, Jeffs E, Vollam S, Watkinson P. A qualitative exploration of escalation of care in the acute ward setting. Nursing in Critical Care. 2020;25:171–178. 3. Louch G, Albutt A, Harlow-Trigg J, Moore S, Smyth K, Ramsey L, O’Hara JK. Exploring patient safety outcomes for people with learning disabilities in acute hospital settings: a scoping review. BMJ Open 2021;11:47102.

From Processivity to Genome Maintenance: The Many Roles of Sliding Clamps

Sliding clamps play a pivotal role in the process of replication by increasing the processivity of the replicative polymerase. They also serve as an interacting platform for a plethora of other proteins, which have an important role in other DNA metabolic processes, including DNA repair. In other words, clamps have evolved, as has been correctly referred to, into a mobile "tool-belt" on the DNA, and provide a platform for several proteins that are involved in maintaining genome integrity. Because of the central role played by the sliding clamp in various processes, its study becomes essential and relevant in understanding these processes and exploring the protein as an important drug target. In this review, we provide an updated report on the functioning, interactions, and moonlighting roles of the sliding clamps in various organisms and its utilization as a drug target.

Activities of Eravacycline, Tedizolid, Norvancomycin, Nemonoxacin, Ceftaroline, and Comparators against 1,871 Staphylococcus and 1,068 Enterococcus Species Isolates from China: Updated Report of the CHINET Study 2019.

To evaluate the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and Enterococcus species isolates were collected as part of the China Antimicrobial Surveillance Network (CHINET) in 2019 to provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice. Antimicrobial susceptibility testing was performed using the CLSI broth microdilution reference method. Eravacycline was highly active against Staphylococcus and Enterococcus species isolates, proved by the MIC50/90: 0.06/0.125, 0.06/0.25, 0.06/0.25, 0.06/0.25, 0.125/0.5, 0.125/0.25, and 0.03/0.06 mg/L for Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, S. hominis, S. haemolyticus, Enterococcus faecalis, and E. faecium, respectively. S. aureus isolates tested were fully susceptible to tedizolid. Still, nonsusceptible isolates were found for E. faecalis (72/567 [12.7%]) and E. faecium (12/501 [2.4%]). Norvancomycin at 2 mg/L could inhibit 100% of Staphylococcus spp., while 1 mg/L of ceftaroline could inhibit 78.9% of MRSA and 99.9% of methicillin-susceptible S. aureus (MSSA) isolates. Additionally, nemonoxacin was also active against Staphylococcus and Enterococcus species isolates tested (shown by the following MIC90s and ranges, in milligrams per liter: 2 and ≤0.015 to 8 for MRSA, 0.25 and ≤0.015 to 4 for MSSA, 0.5 and ≤0.015 to 8 for S. epidermidis, and 4 and ≤0.015 to >32 for E. faecalis). In conclusion, both eravacycline and tedizolid were highly active against clinical isolates of Staphylococcus spp. and Enterococcus spp. recently collected across China. Nemonoxacin showed potent activity against Staphylococcus spp. and E. faecalis but limited activity against E. faecium. Norvancomycin and ceftaroline displayed highly potent activity against Staphylococcus spp. IMPORTANCE Antimicrobial resistance has become a severe threat to global public health. According to statistics, nearly 700,000 people die from bacterial infections worldwide (J. O'Neill, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations, 2014; C. Y. Chin, K. A. Tipton, M. Farokhyfar, E. M. Burd, et al., Nat Microbiol 3:563-569, 2018, https://doi.org/10.1038/s41564-018-0151-5). The number of bacterial infections is expected to climb to 10 million by 2050, showing that bacterial resistance has become a significant problem that cannot be ignored. It is crucial to develop new antimicrobial agents to combat antimicrobial-resistant bacteria. In this study, we evaluated the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus spp. and Enterococcus species isolates which were collected as part of CHINET in 2019. We believe that this study can provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice.