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Introduction Many patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine (lignocaine) has the potential to help manage neuropathic cancer-related pain when administered as an extended, continuous subcutaneous infusion. Data support lidocaine as a promising, safe agent in this setting, warranting further evaluation in robust, randomised controlled trials. This protocol describes the design of a pilot study to evaluate this intervention and explains the pharmacokinetic, efficacy and adverse effects evidence informing the design.Methods and analysis A mixed-methods pilot study will determine the feasibility of an international first, definitive phase III trial to evaluate the efficacy and safety of an extended continuous subcutaneous infusion of lidocaine for neuropathic cancer-related pain. This study will comprise: a phase II double-blind randomised controlled parallel-group pilot of subcutaneous infusion of lidocaine hydrochloride 10% w/v (3000 mg/30 mL) or placebo (sodium chloride 0.9%) over 72 hours for neuropathic cancer-related pain, a pharmacokinetic substudy and a qualitative substudy of patients’ and carers’ experiences. The pilot study will provide important safety data and help inform the methodology of a definitive trial, including testing proposed recruitment strategy, randomisation, outcome measures and patients’ acceptability of the methodology, as well as providing a signal of whether this area should be further investigated.Ethics and dissemination Participant safety is paramount and standardised assessments for adverse effects are built into the trial protocol. Findings will be published in a peer-reviewed journal and presented at conferences. This study will be considered suitable to progress to a phase III study if there is a completion rate where the CI includes 80% and excludes 60%. The protocol and Patient Information and Consent Form have been approved by Sydney Local Health District (Concord) Human Research Ethics Committee 2019/ETH07984 and University of Technology Sydney ETH17-1820.Trial registration number ANZCTR ACTRN12617000747325.

Saphenous vein graft (SVG) pseudoaneurysms are an infrequent, but life-threatening complication of coronary artery bypass grafting (CABG) surgery if left untreated. Here, we discuss the case of a 77-year-old patient, with a prior history of CABG and transcatheter aortic valve implantation (TAVI), who was incidentally found on computed tomography angiography (CTA) to have a pseudoaneurysm of his SVG with an initial chief complaint of dizziness. Despite increasing reports of SVG pseudoaneurysm, there is no consensus on definitive treatment. Due to the high mortality risk of this patient with surgical intervention, a minimally invasive percutaneous coronary intervention was performed. The patient was effectively treated with two overlapping Viabahn-covered stents, which completely excluded the pseudoaneurysm. Follow-up imaging at two months showed two well-positioned overlapping self-expanding stents with total occlusion of the pseudoaneurysm.

Abstract Arthropod vectors play a crucial role in the transmission of hemotropic mycoplasmas, small bacteria that infect red blood cells in a wide range of animals and humans globally, leading to intravascular infections. Traditional Giemsa-stained thin blood smears, used for diagnosing hemotropic mycoplasmas through microscopic examination, have low sensitivity and are effective only when bacteremia levels are high. This study aimed to employ molecular methods to detect and genetically characterize hemotropic mycoplasmas in goats as well as investigate the potential role of fleas as vectors. Blood and flea samples were collected concurrently from goats on 16 farms across seven provinces in Thailand from January 2017 to October 2023. The 16 S rRNA, 23 S rRNA, and rnpB genes of hemoplasmas were amplified and sequenced. All fleas were identified morphologically and molecularly through DNA barcoding of the cytochrome oxidase I gene. A total of 78 out of 500 goats (15.6%), three pooled flea samples (3/6, 50%), and one individual flea (1/49, 2.04%) tested positive for hemoplasmas and all fleas were identified as Ctenocephalides orientis. BLASTN searches utilizing the three genetic markers revealed that the hemoplasmas detected in this study showed 97.81–100% similarity to Mycoplasma ovis and Candidatus Mycoplasma haemovis, which have been previously reported in sheep, goats, and humans, suggesting their zoonotic potential. The sequences were grouped into 28 unique nucleotide sequence types (ntSTs) based on minor variations in the 16 S rRNA gene. Hemotropic mycoplasma infection was significantly associated with farm locations and seasonality of sample collection (p

Introduction The global prevalence of people living with overweight has tripled since 1975 and more than 40% of Danish women enter pregnancy being overweight. With the increasing rates of obesity observed in children, adolescents and adults, there is an urgent need for preventive measures. Risk factors for childhood obesity include maternal overweight or obesity before conception and excessive weight gain during pregnancy. Interventions aimed at modifying maternal lifestyle during pregnancy have demonstrated minimal positive or no impact on the health of the children. The ‘healthy lifestyle before and during pregnancy to prevent childhood obesity — the PRE-STORK trial’ aims to provide insights into the effect of a lifestyle intervention initiated before conception and continued during pregnancy in women with overweight or obesity, on neonatal adiposity in their children.Methods and analysis In this randomised, two-arm, parallel-group, controlled trial, we will include 360 women with overweight or obesity (aged 18–40; body mass index 25–44 kg/m2) and their partners. The women will be randomised to receive either standard of care or a lifestyle intervention focused on preconception body weight reduction, regular physical exercise, healthy diet and support from a mentor before and during pregnancy. The primary outcome is the difference in neonatal adiposity measured in their children at birth. Children conceived during the trial will constitute a birth cohort, monitoring the effects on their health until the age of 18 years.Ethics and dissemination The trial has been approved by the Regional Committee on Health Research Ethics in the Capital Region of Denmark (identification number H-22011403) and will be conducted in agreement with the Declaration of Helsinki. All results, whether positive, negative and inconclusive, will be disseminated at national or international scientific meetings and in peer-reviewed scientific journals.Trial registration number ClinicalTrials.gov: NCT05578690 (October 2022).

Objective: To perform a systematic literature review analyzing visual outcomes of immediate, early, and delayed vitrectomy in the treatment of acute endophthalmitis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Methods: We conducted a literature search using the Ovid Medline, Embase.com, and Web of Science databases, and relevant articles were selected from original English papers published from 2005 to 2021. Inclusion criteria were studies reporting cases of acute post-anti-VEGF endophthalmitis, defined as occurring within 6 weeks of injection treatment. Exclusion criteria were pediatric cases and cases explicitly reported to be caused by injections of contaminated drugs. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tool for case reports and case series. The study dataset for descriptive and statistical analysis comprised patient-level data extracted from included studies. The timing of vitrectomy compared were defined as (1) immediate vitrectomy as occurring within 24 h of endophthalmitis diagnosis; (2) early vitrectomy as occurring between 24 and 48 h of endophthalmitis diagnosis; (3) late vitrectomy as occurring after 48 h of endophthalmitis diagnosis. Primary outcome was final visual acuity following treatment with vitrectomy. Results: Twenty-five articles were published that met our inclusion and exclusion criteria for a total of 86 cases. Thirty-seven were immediate vitrectomy, 25 were early, and 24 were late vitrectomy treatment groups, respectively. We observed differences in final visual outcomes and in improvement from diagnosis to final visual acuity, with patients receiving immediate and late vitrectomy to have better final visual outcomes than those patients receiving early vitrectomy ( p

Background: Mechanical low back pain is the pain in the lumbar area caused by aberrant stresses on the spine's vertebrae, ligaments, soft tissues, intervertebral discs, muscles and other soft tissues Objective: To determine the association between non-specific mechanical low back pain and limited ankle dorsiflexion among female students. Methodology: This cross-sectional study was conducted at Agile Institute of Rehabilitation Sciences from November 2021-March 2022. A total of 133 female students of age 18-30 years were included in this study. Students wearing high heels were excluded. The data was collected using Numeric Pain Rating Scale questionnaire for low back pain and goniometry for measuring ankle dorsiflexion. Data was analyzed using Statistical Package for Social Sciences version 22.0 to create graphs and tables. Chi square test was used for statistical analysis to find the association between low back pain and limited ankle dorsiflexion. Results: A total of 133 participants were screened for low back pain. Out of total, 61 (45.86%) participants with mechanical low back pain had limited ankle dorsiflexion range of motion (≤10 degree) on left side while 64 (48.12%) participants with mechanical low back pain had limited ankle dorsiflexion range of motion (≤10 degree) on right side ankle. P value of chi square association of low back pain and ankle dorsiflexion was 0.078 for right ankle and 0.114 for left ankle. Conclusions: This study concluded that there was no association found between non-specific mechanical low back pain and limited ankle dorsiflexion range of motion. Keywords: Ankle joint, Dorsiflexion, Mechanical Low Back Pain

Background As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. Methods Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. Results Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred 30%) in some datasets—limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. Conclusion Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources–a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

Background Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. Methods Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. Results A total of 15,615 people were observed to have at least one serology test 14–90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79–96%) compared to non-Hispanic (60–89%) patients; in those presenting with at least one COVID-19 related symptom (69–93%) as compared to no such symptoms (63–91%); and in inpatient (70–97%) and emergency department (93–99%) compared to outpatient (63–92%) settings across datasets. PPA was highest in those with diabetes (75–94%) and kidney disease (83–95%); and lowest in those with auto-immune conditions or who are immunocompromised (56–93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59–3.86), patients with diabetes (1.49–1.56), and obesity (1.63–2.23); and lower in those with immunocompromised or autoimmune conditions (0.25–0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. Conclusion Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

Brain tumors necessitate swift detection and classification for optimal patient outcomes. Deep learning has been extensively utilized to recognize complex tumor patterns in magnetic resonance imaging (MRI) images, aiding in tumor diagnosis, treatment, and prognostication. However, model complexity and limited generalizability with unfamiliar data hinder appropriate clinical integration. The objective of this study is to develop a clean-energy cloud-based deep learning platform to classify brain tumors. Three datasets of a total of 2611 axial MRI images were used to train our multi-layer convolutional neural network (CNN). Our platform automatically optimized every transfer learning and data augmentation feature combination to provide the highest predictive accuracy for our classification task. Our proposed system identified and classified brain tumors successfully and efficiently with an overall precision value of 96.8% [95% CI; 93.8–97.6]. Using clean energy supercomputing resources and cloud platforms cut our workflow to 103 min, $0 in total cost, and a negligible carbon footprint (0.0014 kg eq CO2). By leveraging automated optimized learning, we developed a cost-effective deep learning (DL) platform that accurately classified brain tumors from axial MRI images of different levels. Although studies have identified machine learning tools to overcome these obstacles, only some are cost-effective, generalizable, and usable regardless of experience.

Generative-AI (GAI) models like ChatGPT are becoming widely discussed and utilized tools in medical education. For example, it can be used to assist with studying for exams, shown capable of passing the USMLE board exams. However, there have been concerns expressed regarding its fair and ethical use. We designed an electronic survey for students across North American medical colleges to gauge their views on and current use of ChatGPT and similar technologies in May, 2023. Overall, 415 students from at least 28 medical schools completed the questionnaire and 96% of respondents had heard of ChatGPT and 52% had used it for medical school coursework. The most common use in pre-clerkship and clerkship phase was asking for explanations of medical concepts and assisting with diagnosis/treatment plans, respectively. The most common use in academic research was for proof reading and grammar edits. Respondents recognized the potential limitations of ChatGPT, including inaccurate responses, patient privacy, and plagiarism. Students recognized the importance of regulations to ensure proper use of this novel technology. Understanding the views of students is essential to crafting workable instructional courses, guidelines, and regulations that ensure the safe, productive use of generative-AI in medical school.

Background: Wastewater is a major source of Antibiotic-Resistant Bacteria (ARB) and a hotspot for the exchange of Antibiotic-Resistant Genes (ARGs). The occurrence of Carbapenem-Resistant Bacteria (CRB) in wastewater samples is a major public health concern. Objectives: This study aimed to analyze Antibiotic resistance in bacteria from wastewater sources in Pakistan. Methods: We analyzed 32 bacterial isolates, including 18 Escherichia coli, 4 Klebsiella pneumoniae, and 10 other bacterial isolates using phenotypic antibiotic susceptibility assay and whole-genome sequencing. This study identified the ARGs, plasmid replicons, and integron genes cassettes in the sequenced isolates. One representative isolate was further sequenced using Illumina and Oxford nanopore sequencing technologies. Results: Our findings revealed high resistance to clinically important antibiotics: 91% of isolates were resistant to cefotaxime, 75% to ciprofloxacin, and 62.5% to imipenem, while 31% showed non-susceptibility to gentamicin. All E. coli isolates were resistant to cephalosporins, with 72% also resistant to carbapenems. Sequence analysis showed a diverse resistome, including carbapenamases (blaNDM-5, blaOXA-181), ESBLs (blaCTX-M-15, blaTEM), and AmpC-type β-lactamases (blaCMY). Key point mutations noticed in the isolates were pmrB_Y358N (colistin) and ftsI_N337NYRIN, ftsI_I336IKYRI (carbapenem). The E. coli isolates had 11 different STs, with ST410 predominating (28%). Notably, the E. coli phylogroup A isolate 45EC1, (ST10886) is reported for the first time from wastewater, carrying blaNDM-5, blaCMY-16, and pmrB_Y358N with class 1 integron gene cassette of dfrA12-aadA2-qacEΔ1 on a plasmid-borne contig. Other carbapenamase, blaNDM-1 and blaOXA-72, were detected in K. pneumoniae 22EB1 and Acinetobacter baumannii 51AC1, respectively. The integrons with the gene cassettes encoding antibiotic resistance, and the transport and bacterial mobilization protein, were identified in the sequenced isolates. Ten plasmid replicons were identified, with IncFIB prevalent in 53% of isolates. Combined Illumina and Oxford nanopore sequencing revealed blaNDM-5 on an IncFIA/IncFIC plasmid and is identical to those reported in the USA, Myanmar, and Tanzania. Conclusions: These findings highlight the environmental prevalence of high-risk and WHO-priority pathogens with clinically important ARGs, underscoring the need for a One Health approach to mitigate ARB isolates.

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

Objective: To assess the effectiveness of functional endoscopies sinus surgery in improving olfaction in patients diagnosed with chronic rhinosinusitis with nasal polyps, as measured by changes in Sniffin’s Stick scores and olfaction scores pre and post operatively. Methodology: The clinical observational study was conducted at the ENT department, Services Hospital, Lahore for 6 months from 01-03-2022 to 31-08- 2022. Sixty-six patients (66) diagnosed with chronic rhinosinusitis with nasal polyps were enrolled, and evaluated by using Sniffin’s Stick score and olfaction baseline score. The inclusion criteria were patients aged 10-60 years of age diagnosed with this condition and willing to undergo surgery. Operative time was noted. After surgery, patients were discharged and were followed-up in OPD for 3 months. After 3 months, patients were re-evaluated for Sniffin’s Stick score and olfaction score. Results: The mean age of the patients was 36.18±13.87 years, 49(74.24%) patients were male. On pre-op evaluation the mean Sniffin’s Stick score of the patients was 6.14±0.41 which improved to 7.34±0.41 on postop evaluation. Similarly on pre-op evaluation the mean olfaction score of the patients was 8.30±5.84 which improved to 21.12±5.95 on post-op evaluation. Conclusion: There is significant improved outcome observed in terms snuffiness and olfaction score for functional endoscopic sinus surgery in patents of chronic rhino-sinusitis with nasal polyps