Development of Mupirocin-Impregnated Bacterial Cellulosic Transdermal Patches for the Management of Skin Infection.

The present study reports the production of bacterial cellulose (BC) membranes using Komagataeibacter hansenii for the development of transdermal wound healing patches. BC-based transdermal patches were developed by impregnating varied concentrations of antibiotic mupirocin and characterized by SEM, FTIR, TGA, and DSC to study the interaction of BC with antibiotic. Developed patches were evaluated for antimicrobial activity, in vitro drug release study, in vivo efficacy, and acute dermal toxicity studies. The antibacterial activity of mupirocin-impregnated patches (mup-BC) showed an inhibition zone from 26.16 ± 0.76 to 35.86 ± 0.61 mm. The in vivo efficacy of mup-BC patches on the superficial abrasion mouse model infected with MRSA 15187 was determined. A single application of the mup-BC (Batch-3) showed a significant decrease up to 2.5 log10 colony-forming units (CFUs) in the infected skin. Acute dermal toxicity study showed no notable sign of toxicity. Pharmacokinetic study indicated that an application of mup-BC (Batch-3) showed a peak plasma concentration of around 1.5 µg/mL mupirocin. The overall preparation, ease of application, and efficacy results clearly indicate that the patches developed in the present study find immense application in the healthcare sector, especially for the treatment of burn or dermal wound infections.

Exploring the Antibacterial Potential of Semisynthetic Phytocannabinoid: Tetrahydrocannabidiol (THCBD) as a Potential Antibacterial Agent against Sensitive and Resistant Strains of Staphylococcus aureus.

Antimicrobial resistance (AMR) is one of the most challenging problems and is responsible for millions of deaths every year. We therefore urgently require new chemical entities with novel mechanisms of action. Phytocannabinoids have been adequately reported for the antimicrobial effect but not seriously pursued because of either stringent regulatory issues or poor drug-like properties. In this regard, the current work demonstrated the antibacterial potential of tetrahydrocannabidiol (THCBD, 4), a semisynthetic phytocannabinoid, against Staphylococcus aureus, the second-most widespread bug recognized by the WHO. THCBD (4) was generated from cannabidiol and subjected to extensive antibacterial screening. In in vitro studies, THCBD (4) demonstrated a potent MIC of 0.25 µg/mL against Gram-positive bacteria, S. aureus ATCC-29213. It is interesting to note that THCBD (4) has demonstrated strong effectiveness against efflux pump-overexpressing (SA-1199B, SA-K2191, SA-K2192, and Mupr-1) and multidrug-resistant (MRSA-15187) S. aureus strains. THCBD (4) has also shown a good effect in kill kinetic assays against ATCC-29213 and MRSA-15187. In the checkerboard assay, THCBD (4) has shown additive/indifference effects with several well-known clinically used antibiotics, tetracycline, mupirocin, penicillin G, and ciprofloxacin. THCBD (4) also exhibited good permeability in the artificial skin model. Most importantly, THCBD (4) has significantly reduced CFU in mice's in vivo skin infection models and also demonstrated decent plasma exposure with 16-17% oral bioavailability. Acute dermal toxicity of THCBD (4) suggests no marked treatment-related impact on gross pathophysiology. This attractive in vitro and in vivo profile of plant-based compounds opens a new direction for new-generation antibiotics and warrants further detailed investigation.

Association of serum beta hCG levels in women with palpable malignant breast lesions.

This study aims to determine whether serum Beta hCG can be used as a tumour marker in Breast malignancies. The objective of this study is to evaluate the serum Beta hCG in various stages of breast carcinoma and to correlate its level with disease severity and prognosis. Cross sectional analytical study of assessing serum Beta hCG in 200 patients with palpable breast malignancies at hospitals in urban Mangalore, India. In our study there was No increase in serum Beta hCG, in women with breast malignancies, but there was a pattern amongst the negative results. A Beta hCG of < 5mIU/mL is taken as negative, but in our study of 200 individuals, a mean value of 2mIU/mL was used as differentiation between low and high risk individuals. With our study we tried to correlate the value of Beta hCG with malignant breast lesions, and even though women with such lesions did not have a value of > 5mIU/mL, we found substantial evidence that women who had a value of > 2mIU/mL had a more advanced disease, be it in terms of staging, and comparing it with markers like ki67. A direct correlation between Beta hCG and severity of the disease in terms of staging was proved, hereby directly affecting the outcome of patients. Higher the level of Beta hCG, graver the prognosis. Even though Beta hCG cannot be used as tumour marker, it can be used to prognosticate the severity in women with palpable breast malignancies.

High sensitivity troponin - Six hours is the magic number.

BACKGROUND: High sensitivity troponin assays have become widespread for emergency department evaluation of acute chest pain. We assessed if a high sensitivity troponin under the 99th percentile upper reference limit drawn at 6 h or greater from symptom onset could safely rule out acute coronary syndrome in patients who did not meet the rapid rule-out strategy. METHODS: We conducted a multicenter retrospective study examining emergency department patients with chest pain who did not meet rapid-rule out criteria and were admitted for further evaluation. Among these admitted patients, we assessed the rate of clinically relevant adverse cardiac events (death, cardiac or respiratory arrest, STEMI, or life-threatening arrhythmia) and NSTEMI in patients with high sensitivity troponin less than the 99th percentile value obtained after at least 6 h of chest pain. RESULTS: Out of 1187 patients admitted, we found 30 clinically relevant adverse cardiac events, all of which occurred in patients admitted for another compelling reason or ischemic ECG. 36 patients had an NSTEMI, of which 33 were identified with high sensitivity troponin greater than 99th percentile upper reference limit within 6 h of chest pain onset. This left 0 clinically relevant adverse cardiac events and 3 NSTEMI among the 429 patients with high sensitivity troponin less than the 99th percentile at 6 h and nonischemic ECG and no other compelling reason for admission. CONCLUSION: This study assessed patients with chest pain with high sensitivity troponin values between 3 ng/L and the 99th percentile upper reference limit after 6 h of chest pain and found that they have a low rate of clinically relevant adverse cardiac events and NSTEMI.

Left sided Amyand hernia - A case report.

INTRODUCTION: Amyand hernia is a clinical condition wherein content of the inguinal hernial sac is formed by the vermiform appendix. CASE PRESENTATION: 1 year 3-month-old male child presented to our OPD with an irreducible left inguinal hernia for which he was taken up for an emergency herniotomy. The terminal ileum, caecum and appendix were found to be the contents of the hernial sac. DISCUSSION: As the appendix is anatomically located on the right, Amyand hernia more commonly occurs on the right, however its occurrence on the left, is a rare event and is usually associated with congenital anomalies like Intestinal malrotation, Situs inversus and mobile caecum. CONCLUSION: Amyand hernia presenting on the left is extremely rare and high index of clinical suspicion is required to manage such patients. We report one such rare case of a Left sided Amyand hernia in a young child.

Utility of severity assessment tools in COVID-19 pneumonia: a multicentre observational study.

BACKGROUND: Severity scores in pneumonia and sepsis are being applied to SARS-CoV-2 infection. We aimed to assess whether these severity scores are accurate predictors of early adverse outcomes in COVID-19. METHODS: We conducted a multicentre observational study of hospitalised SARS-CoV-2 infection. We assessed risk scores (CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2) in relation to admission to intensive care or death within 7 days of admission, defined as early severe adverse events (ESAE). The 4C Mortality Score was also assessed in a sub-cohort of patients. FINDINGS: In 2,387 participants, the overall mortality was 18%. In all scores examined, increasing score was associated with increased risk of ESAE. Area under the curve (AUC) to predict ESAE for CURB65, qSOFA, Lac-CURB65, MuLBSTA and NEWS2 were 0.61, 0.62, 0.59, 0.59 and 0.68, respectively. AUC to predict ESAE was 0.60 with ISARIC 4C Mortality Score. CONCLUSION: None of the scores examined accurately predicted ESAE in SARS-CoV-2 infection. Non-validated scores should not be used to inform clinical decision making in COVID-19.

The utility of surgical Apgar score in predicting postoperative morbidity and mortality in general surgery.

Objectives: Many surgical scoring systems are used to predict operative risk but most are complicated. The aim of the study was to determine the utility of the Surgical Apgar Score (SAS) in predicting post operative mortality and morbidity in general surgical cases. Material and Methods: This was a prospective observational study. All adult patients for emergency and elective general surgical procedures were included. Intraoperative data was collected, and post operative outcomes were followed up till 30 days. SAS was calculated from intraoperative lowest heart rate, lowest MAP and blood loss. Results: A total of 220 patients were included in the study. All consecutive general surgical procedures were included. Sixty of the 220 cases were emergency and the rest were elective. Forty-five (20.5%) of the patients developed complication. Mortality rate was 3.2% (7 out of 220). The cases were divided into high risk (0-4), moderate risk (5-8) and low risk (9-10) based on SAS. Complication and mortality rates were 50% and 8.3% in the high risk group, 23% and 3.7% in the moderate risk and 4.2% and 0 in the low risk group, respectively. Conclusion: The surgical Apgar score is a simple and valid predictor of postoperative morbidity and 30-day mortality among patients undergoing general surgeries. It is applicable to all types of surgeries for emergency and elective cases and irrespective of the patient general condition and type of anesthesia and surgery planned.

Optimization and validation of RT-LAMP assay for diagnosis of SARS-CoV2 including the globally dominant Delta variant.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 pandemic, has infected more than 179 million people worldwide. Testing of infected individuals is crucial for identification and isolation, thereby preventing further spread of the disease. Presently, Taqman™ Reverse Transcription Real Time PCR is considered gold standard, and is the most common technique used for molecular testing of COVID-19, though it requires sophisticated equipments, expertise and is also relatively expensive. OBJECTIVE: Development and optimization of an alternate molecular testing method for the diagnosis of COVID-19, through a two step Reverse Transcription Loop-mediated isothermal AMPlification (RT-LAMP). RESULTS: Primers for LAMP were carefully designed for discrimination from other closely related human pathogenic coronaviruses. Care was also taken that primer binding sites are present in conserved regions of SARS-CoV2. Our analysis shows that the primer binding sites are well conserved in all the variants of concern (VOC) and variants of interest (VOI), notified by World Health Organization (WHO). These lineages include B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526 and B.1.617.1. Various DNA polymerases with strand displacement activity were evaluated and conditions were optimized for LAMP amplification and visualization. Different LAMP primer sets were also evaluated using synthetic templates as well as patient samples. CONCLUSION: In a double blind study, the RT-LAMP assay was validated on more than 150 patient samples at two different sites. The RT-LAMP assay appeared to be 89.2% accurate when compared to the Taqman™ rt-RT-PCR assay.

Rare presentation of rectal duplication cyst as perineal hernia in an adult.

Rectal duplication cysts are rare congenital anomalies of the gastrointestinal tract. They can present with pain, gastrointestinal bleeding, infection or compressive symptoms on the rectum and urinary bladder. A 79-year-old man presented with a 8×5 cm swelling in the sacral region above the natal cleft with a positive cough impulse. During surgical exploration, there were two cysts with the posterior one presenting as the hernia. The cyst was excised and histopathological examination confirmed a diagnosis of rectal duplication cyst. Rectal duplications can lie anterior or more commonly posterior to the rectum. Differential diagnoses include dermoid cyst, diverticular cyst, sacrococcygeal teratoma or meningocele and endoscopic ultrasound is imaging of choice for diagnosis. Surgical excision is the treatment of choice. This is a rare presentation of a rectal duplication cyst as a perineal hernia with only a handful of cases in literature.

Learner Perceptions of Electronic End-of-shift Evaluations on An Emergency Medicine Clerkship.

OBJECTIVES: As students on an emergency medicine (EM) rotation work with different faculty on a daily basis, EM clerkships often incorporate an end-of-shift evaluation to capture sufficient student performance data. Electronic shift evaluations have been shown to increase faculty completion compliance. This study aimed to examine learner perceptions of their individualized feedback during an EM clerkship following the adoption of an electronic evaluation tool. METHODS: This retrospective study examined end-of-rotation surveys that students complete at the conclusion of their EM rotation. Survey respondents used a standard Likert scale (1-5). This study examined responses to the question: "The feedback I received on this rotation was adequate." The study period included the 3 academic years prior to and subsequent to the adoption of an electronic evaluation system (replacing paper end-of-shift evaluations). The primary outcome was the mean Likert score and the secondary outcome was the percentage of students who rated their feedback a "5" or "strongly agree." RESULTS: A total of 491 students responded (83.9% response rate) to the survey during the paper evaluation period, while 427 responded (80.7% response rate) in the electronic period. The mean response improved from 4.02 (paper evaluations) to 4.22 (electronic evaluations; mean difference = 0.20, p < 0.05). The percentage of students who responded with a 5 improved (31% with paper evaluations vs. 41% with electronic evaluations, p < 0.05). CONCLUSIONS: The adoption of an electronic end-of-shift evaluation system was associated with improved learner perception of their feedback as compared to paper evaluations. Electronic evaluations are a useful tool to gather just-in-time data on learner performance.

Preliminary Assessment of a Telehealth Approach to Evaluating, Treating, and Discharging Low-Acuity Patients With Suspected COVID-19.

BACKGROUND: Telemedicine is uniquely positioned to address challenges posed to emergency departments (EDs) by the Coronavirus Disease 2019 (COVID-19) pandemic. By reducing in-person contact, it should decrease provider risk of infection and preserve personal protective equipment (PPE). OBJECTIVES: To describe and assess the early results of a novel telehealth workflow in which remote providers collaborate with in-person nursing to evaluate and discharge well-appearing, low-risk ED patients with suspected COVID-19 infection. METHODS: Retrospective chart review was completed 3 weeks after implementation. Metrics include the number of patients evaluated, number of patients discharged without in-person contact, telehealth wait time and duration, collection of testing, ED length of stay (ED-LOS), 72-h return, number of in-person health care provider contacts, and associated PPE use. RESULTS: Among 302 patients evaluated by telehealth, 153 patients were evaluated and discharged by a telehealth provider with reductions in ED-LOS, PPE use, and close contact with health care personnel. These patients had a 62.5% shorter ED-LOS compared with other Emergency Severity Index level 4 patients seen over the same time period. Telehealth use for these 153 patients saved 413 sets of PPE. We observed a 3.9% 72-h revisit rate. One patient discharged after telehealth evaluation was hospitalized on a return visit 9 days later. CONCLUSION: Telehealth can be safely and efficiently used to evaluate, treat, test, and discharge ED patients suspected to have COVID-19. This workflow reduces infection risks to health care providers, PPE use, and ED-LOS. Additionally, it allows quarantined but otherwise well clinicians to continue working.

High-throughput screening of compounds library to identify novel inhibitors against latent Mycobacterium tuberculosis using streptomycin-dependent Mycobacterium tuberculosis 18b strain as a model.

One of the significant challenges to treat tuberculosis is the phenotypic resistance adapted by the latent or dormant Mycobacterium tuberculosis (M. tuberculosis) cells against most of the available drugs. Different in-vitro assay such as oxygen depletion model and nutrient starvation models have contributed to unravelling the pathogen phenotypic resistance but are too cumbersome for application to high-throughput screening (HTS) assays. In this context, non-replicating streptomycin-starved 18b (SS18b) mutant strain of M. tuberculosis provided a simple and reproducible model. This model mimics latent tuberculosis and is best suited for screening medicinally appropriate libraries. Using SS18b strain in a resazurin reduction microplate assay (REMA), high-throughput screening of ChemDiv library constituting of 30,000 compounds resulted in the identification of 470 active compounds. Clustering and scaffolding based medicinal chemistry analysis characterized these hits into 15 scaffolds. Seven most potent compounds exhibiting an MIC ≤ 1 µg/ml against SS18b were non-toxic in HepG2 cell line (selective Index ≥ 160). Our screening revealed seven novel compounds exhibiting activity against the non-replicating form of M tuberculosis. 8002-7516 was the most promising compound showing intracellular killing and could be optimized to develop a lead drug candidate.

Screening of Antitubercular Compound Library Identifies Inhibitors of Mur Enzymes in Mycobacterium tuberculosis.

The rapid rise in the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) mandates the discovery of novel tuberculosis (TB) drugs. Mur enzymes, which are identified as essential proteins in Mtb and catalyze the cytoplasmic steps in the peptidoglycan biosynthetic pathway, are considered potential drug targets. However, none of the clinical drugs have yet been developed against these enzymes. Hence, the aim of this study was to identify novel inhibitors of Mur enzymes in Mycobacterium tuberculosis. We screened an antitubercular compound library of 684 compounds, using MurB and MurE enzymes of the Mtb Mur pathway as drug targets. For experimental validation, the top hits obtained on in silico screening were screened in vitro, using Mtb Mur enzyme-specific assays. In all, seven compounds were found to show greater than 50% inhibition, with the highest inhibition observed at 77%, and the IC50 for these compounds was found to be in the range of 28-50 µM. Compound 5175112 showed the lowest IC50 (28.69 ± 1.17 µM), and on the basis of (1) the binding affinity, (2) the stability of interaction noted on molecular dynamics simulation, and (3) an in vitro assay, MurE appeared to be its target enzyme. We believe that the overall strategy followed in this study and the results obtained are a good starting point for developing Mur enzyme-specific Mtb inhibitors.

Integration of Entrustable Professional Activities with the Milestones for Emergency Medicine Residents.

INTRODUCTION: Medical education is moving toward a competency-based framework with a focus on assessment using the Accreditation Council for Graduate Medical Education Milestones. Assessment of individual competencies through milestones can be challenging. While competencies describe characteristics of the person, the entrustable professional activities (EPAs) concept refers to work-related activities. EPAs would not replace the milestones but would be linked to them, integrating these frameworks. Many core specialties have already defined EPAs for resident trainees, but EPAs have not yet been created for emergency medicine (EM). This paper describes the development of milestone-linked EPAs for EM. METHODS: Ten EM educators from across North America formed a consensus working group to draft EM EPAs, using a modified Glaser state-of-the-art approach. A reactor panel with EPA experts from the United States, Canada and the Netherlands was created, and an iterative process with multiple revisions was performed based on reactor panel input. Following this, the EPAs were sent to the Council of Residency Directors for EM (CORD-EM) listserv for additional feedback. RESULTS: The product was 11 core EPAs that every trainee from every EM program should be able to perform independently by the time of graduation. Each EPA has associated knowledge, skills, attitudes and behaviors (KSAB), which are either milestones themselves or KSABs linked to individual milestones. We recognize that individual programs may have additional focus areas or work-based activities they want their trainees to achieve by graduation; therefore, programs are also encouraged to create additional program-specific EPAs. CONCLUSION: This set of 11 core, EM-resident EPAs can be used as an assessment tool by EM residency programs, allowing supervising physicians to document the multiple entrustment decisions they are already making during clinical shifts with trainees. The KSAB list within each EPA could assist supervisors in giving specific, actionable feedback to trainees and allow trainees to use this list as an assessment-for-learning tool. Linking each KSAB to individual EM milestones allows EPAs to directly inform milestone assessment for clinical competency committees. These EPAs serve as another option for workplace-based assessment, and are linked to the milestones to create an integrated framework.

2018 Academic Emergency Medicine Consensus Conference: Advancing Pediatric Emergency Medicine Education Through Research and Scholarship.

To achieve high-quality emergency care for pediatric patients nationwide, it is necessary to define the key elements for pediatric emergency medicine (PEM) education and scholarship that would: 1) close the gaps in fundamental PEM education and 2) promote systems and standards that assure an ongoing communication of best practices between tertiary pediatric institutions, general (nonchildren's) hospital emergency departments, and urgent care centers. A working group of medical educators was formed to review the literature, develop a framework for consensus discussion at the breakout session, and then translate their findings into recommendations for future research and scholarship. The breakout session consensus discussion yielded many recommendations. The group concluded that future progress depends on multicenter collaborations as a PEM education research network and a unified vision for PEM education that bridges organizations, providers, and institutions to assure the best possible outcomes for acutely ill or injured children.

Emergency Department Computed Tomography Use for Non-traumatic Abdominal Pain: Minimal Variability.

INTRODUCTION: Variability in the use of computed tomography (CT) between providers in the emergency department (ED) suggests that CT is ordered on a provider rather than a patient level. We aimed to evaluate the variability of CT ordering practices for non-traumatic abdominal pain (NTAP) across physicians in the ED using patient-visit and physician-level factors. METHODS: We conducted a retrospective study among 6,409 ED visits for NTAP from January 1 to December 31, 2012, at a large, urban, academic, tertiary-care hospital. We used a two-level hierarchical logistic regression model to estimate inter-physician variation. Intraclass correlation coefficient (ICC) was calculated. RESULTS: The hierarchical logistic regression analyses showed that patient-visit factors including younger age, arrival mode by ambulance, prior CT, >79 ED arrivals in the previous four hours, and ultrasound had statistically significant negative associations with physician CT ordering, while surgical team admission and white blood count (WBC) >12.5 K/millimeter cubed (mm3) had statistically significant positive associations with physician CT ordering. With physician-level factors, only physicians with >21 years experience after medical school graduation showed statistical significance negatively associated with physician CT ordering. Our data demonstrated increased CT ordering from the mean in only one out of 43 providers (2.3%), which indicated limited variation across physicians to order CT. After adjusting for patient-visit and physician-level factors, the calculated ICC was 1.46%. CONCLUSION: We found minimal physician variability in CT ordering practices for NTAP. Patient-visit factors such as age, arrival mode, admission team, prior CT, ED arrivals in previous four hours, ultrasound, and WBC count were found to largely influence CT ordering practices.

Diagnostic accuracy of a rapid telemedicine encounter in the Emergency Department.

OBJECTIVES: Emergency Department crowding is an increasing problem, leading to treatment delays and higher risk of mortality. Our institution recently implemented a telemedicine physician intake ("tele-intake") process as a mitigating front-end strategy. Previous studies have focused on ED throughput metrics such as door to disposition; our work aimed to specifically assess the tele-intake model for clinical accuracy. METHODS: We retrospectively reviewed ED visits at a high acuity, tertiary care academic hospital before and after tele-intake implementation. We defined the primary outcome as the degree of additional laboratory, imaging, and medication orders placed by the subsequent ED provider. Our secondary outcomes were the cancellation rate of intake orders and the percentage of encounters where no additional second provider orders were necessary. RESULTS: For in-person and tele-intake physician encounters between September 2015 and February 2017, most labs and diagnostic radiology studies, and approximately half of CT, ultrasound, and pharmacy orders were initiated by the intake physician. We found no significant difference for our primary outcome (p = 0.2449). For both tele-intake and in-person encounters, <1% of orders were cancelled by the second provider. Additionally, 30.8% of in-person and 31.5% of telemedicine patient encounters required no additional orders to make a disposition decision. DISCUSSION: This novel analysis of an innovative patient care model suggests that the benefits of tele-intake as a replacement for in-person physician directed intake are not at the cost of over or under utilization of diagnostic testing or interventions.