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Abstract Background Prognostic indicators for equine multinodular pulmonary fibrosis (EMPF), an interstitial fibrosing lung disease, are poorly described. Hypothesis/Objectives Describe diagnostic findings and outcome predictors for EMPF. Animals Forty‐six adult horses with EMPF. Methods Retrospective multicenter case series from 2009 to 2019. Radiographic (n = 27) and ultrasonographic studies (n = 19) from EMPF horses and bronchoalveolar lavage fluid (BALF) cytology from 6 EMPF and 13 asthma cases were independently reviewed and blinded to diagnosis and outcome. Associations between predictor variables and survival were assessed by predictor screening followed by Fisher's exact and Wilcoxon rank sum tests. Results Primary clinical findings were weight loss (36/46, 78%), increased respiratory effort (33/46, 72%), tachypnea (32/46, 70%), and fever (18/46, 39%). Macrophage atypia was seen in more EMPF than asthmatic horse BALF (67% vs. 8%; P = .02). Equine herpesvirus 5 (EHV‐5) was detected in 24 of 30 (80%) and hyperfibrinogenemia in 25 of 28 (89%) cases. Twenty‐seven of 46 horses (59%) and 11 of 45 (24%) survived to discharge and to 3 months, respectively. Three‐month survival was associated with lower median (range) respiratory rates (30 [24‐36] vs. 41 [30‐60] breaths per minute; P = .04), and higher BALF lymphocyte:neutrophil ratios (4.7 [1.4‐22] vs. 0.47 [0.11‐1.9]; P = .01) and blood lymphocyte counts (1.25 [0.93‐2.55] vs. 0.90 [0.70‐1.24] × 109/L; P = .03). Imaging findings, EHV‐5 detection, and corticosteroid treatment were not associated with survival. Conclusions and Clinical Importance Fever is not a sensitive clinical sign of EMPF. Diagnostic testing should be pursued for horses with increased respiratory rate and effort and weight loss. The prognosis for EMPF horses is poor. Corticosteroid treatment does not improve 3‐month survival.

Abstract Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8–12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9–11, P

Objective: To review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. Methods: Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. Results: Three percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4–5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). Conclusion: In this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.

Abstract Background Bacterial sepsis is the leading cause of death in foals and is associated with hypothalamic‐pituitary‐adrenocortical axis (HPAA) dysfunction. HPAA function can be evaluated by an arginine‐vasopressin (AVP) stimulation test. Hypotheses/Objectives Administration of AVP will stimulate a dose‐dependent rise in systemic adrenocorticotropin‐releasing hormone (ACTH) and cortisol in neonatal foals. There will be no response seen in corticotropin‐releasing hormone (CRH) and baseline AVP will be within reference interval. Animals Twelve neonatal foals,

Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the study analysed 3.16 million COVID-19 patients with at least two prior antibiotic prescriptions. These patients were compared to up to six matched controls without hospitalisation records. A machine learning model categorised patients into ten groups based on their antibiotic exposure history over the three years before their COVID-19 diagnosis. The study found that for COVID-19 patients, the total number of prior antibiotic prescriptions, diversity of antibiotic types, broad-spectrum antibiotic prescriptions, time between first and last antibiotics, and recent antibiotic use were associated with an increased risk of severe COVID-19 outcomes. Patients in the highest decile of antibiotic exposure had an adjusted odds ratio of 4.8 for severe outcomes compared to those in the lowest decile. These findings suggest a potential link between extensive antibiotic use and the risk of severe COVID-19. This highlights the need for more judicious antibiotic prescribing in primary care, primarily for patients with higher risks of infection-related complications, which may better offset the potential adverse effects of repeated antibiotic use.

This study described spatiotemporal changes in health insurance coverage, healthcare access, and reasons for non-insurance among racial/ethnic minority populations in the United States during the COVID-19 pandemic using four national survey datasets. Getis-Ord Gi* statistic and scan statistics were used to analyze geospatial clusters of health insurance coverage by race/ethnicity. Logistic regression was used to estimate odds of reporting inability to access healthcare across two pandemic time periods by race/ethnicity. Racial/ethnic differences in insurance were observed from 2010 through 2019, with the lowest rates being among Hispanic/Latino, African American, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander populations. Pre-pandemic insurance coverage rates were geographically clustered. The percentage of adults citing change in employment status as the reason for non-insurance increased by about 7% after the start of the pandemic, with a small decrease observed among African American adults. Almost half of adults reported reduced healthcare access in June 2020, with 38.7% attributing reduced access to the pandemic; however, by May 2021, the percent of respondents reporting reduced access for any reason and due to the pandemic fell to 26.9% and 12.7%, respectively. In general, racial/ethnic disparities in health insurance coverage and healthcare access worsened during the pandemic. Although coverage and access improved over time, pre-COVID disparities persisted with African American and Hispanic/Latino populations being the most affected by insurance loss and reduced healthcare access. Cost, unemployment, and eligibility drove non-insurance before and during the pandemic.

Abstract Introduction Mental well-being is associated with many mental health symptoms, including depression and health-related quality of life. Digital divide could impact mental health, particularly during the COVID-19 pandemic. Information and communication technology (ICT)-based tools and interventions could effectively provide social support. Intergenerational mentoring between college students and older adults could promote eHealth literacy and self-efficacy, and it is advocated to bridge the digital divide for older adults. However, the effectiveness of an intervention which employs ICT-based tools and intergenerational mentoring strategies (i.e. Digital Buddy) on mental well-being is unclear. Methods This study will employ a multi-centre, cluster-randomized, two-parallel-group, noninferiority, controlled trial design with a 1:1 group allocation ratio. In the intervention group, a Digital Buddy (i.e. a young volunteer) is assigned to a group of older adults in a 1:10 ratio. A series of training sessions for a minimum of 23 h will be provided to the older adults by Digital Buddy, who will also follow through the intervention period with the older participants. The training contents include ICT and mental health care knowledge and skills. The whole intervention period will last for 6 months between 14 sessions. In the control group, participants will receive the usual care. The primary outcome measure is mental well-being. We aim to recruit 292 older participants. Generalized estimating equations (GEE) will be used to examine the effects of the intervention. Ethics and dissemination This trial has been registered at ClinicalTrials.gov (NCT05553730) on 23 September 2022, https://clinicaltrials.gov/ct2/show/NCT05553730 , and all items come from the World Health Organization Trial Registration Data Set. It has been approved by the Research Ethics Committee of Tung Wah College, Hong Kong (reference number: REC2022143). The findings will be disseminated in peer-reviewed journals and presented at international conferences relevant to the subject fields.

Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2–related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD.

Abstract Background The fecal bacterial microbiota of normal foals and foals with enterocolitis has been characterized using next‐generation sequencing technology; however, there are no reports investigating the gut microbiota in foals hospitalized for other perinatal diseases. Objective To describe and compare the fecal bacterial microbiota in healthy and sick foals using next‐generation sequencing techniques. Animals Hospitalized (17) and healthy foals (21). Methods Case‐control study. Fecal samples were collected from healthy and sick foals on admission. Sick foals were further divided into sick nonseptic (SNS, n = 9) and septic (n = 8) foals. After extraction of DNA, the V4 region of the 16 S rRNA gene was amplified using a PCR assay, and the final product was sequenced with an Illumina MiSeq. Results Diversity was significantly lower in healthy than sick foals (P .05). Bacterial membership (AMOVA, P = .06) and structure (AMOVA, P = .33) were not different between healthy and sick foals. Enterobacteriaceae, Enterococcus, and Streptococcus were among the 5 more abundant taxa identified in both groups. Conclusion and Clinical Importance Higher fecal microbiota diversity in sick than healthy foals might suggest a high exposure to environmental microorganisms or an unstable colonic microbiota. The presence of microorganisms causing bacteremia in foals in a high relative abundance in the feces of foals suggests the intestine might play an essential role in the causation of bacteremia in foals.

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4–expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.

Ileus is a common life-threatening problem in horses, and currently available treatments may be ineffective. The purpose of this study was to determine whether bit chewing, a form of sham feeding, decreases the gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) in clinically normal horses in a prospective crossover study. Nine healthy horses were acclimated and fed a standardized diet. Following 24 h of fasting, self-contained video endoscopy capsules and acetaminophen were administered into the stomach via a nasogastric tube. Each horse underwent experimental (bit chewing for 20 min every 6 h) or control (no bit chewing) conditions, with a 3-week minimum washout period between conditions. The horses were enrolled in either part of the study until all video capsules were retrieved and/or 30 days lapsed. The video capsules were recovered from manure, and GET, SITT, and OCTT were determined from a video analysis. Bit chewing significantly decreased OCTT (p = 0.015) compared to the control conditions. Bit chewing decreased GET and SITT, but the differences were not significant. The mean (median) times determined via the video capsule analysis for the bit-chewing conditions were as follows: GET, 2.34 h (2.86 h); SITT, 3.22 h (3.65 h); and OCTT, 5.13 h (6.15 h), and for the control conditions, they were as follows: GET, 3.93 h (5 h); SITT, 3.79 h (4.4 h); and OCTT, 8.02 h (9.92 h). Bit chewing decreased OCTT in healthy horses. Because this segment of the gastrointestinal tract is frequently affected by ileus, bit chewing may be a safe and inexpensive intervention for that condition in horses. Further investigation in clinical patients with ileus is warranted.

BackgroundPolypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.MethodsWe used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.ResultsIn total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.ConclusionsPolypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.

Purpose: Lutetium labelled prostate-specific membrane antigen radioligand therapy (Lu-PSMA RLT) has shown pleasing early results in management of high-volume metastatic castration resistant prostate cancer (mCRPC), but its role in the early treatment of men with only lymph node metastasis (LNM) is unknown. The aim was to assess the outcome of Lu-PSMA RLT earlier in the treatment of men with only LNM. Materials and Methods: Single institution retrospective review of men with only LNM on staging Ga-PSMA PET PSMA who proceeded with Lu-PSMA RLT. Results: There were 17 men with only LNM, including 13 with mCRPC and 3 who were both hormone and chemotherapy naïve. The median PSA was 3.7 (0.46–120 ng/mL). A PSA decline of ≥50% occurred in 10/17 (58.8%), decreasing to

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Abstract Background Monitoring blood glucose concentrations is common in critically ill neonatal foals, especially septic foals and those receiving naso‐esophageal feedings or IV parenteral nutrition. Glucose typically is measured using a point‐of‐care (POC) glucometer but requires repeated restraint and blood collections, which may cause irritation at venipuncture sites and increased demands on nursing staff. Continuous glucose monitoring systems (CGMS) may provide an accurate alternative for monitoring blood glucose concentration. Objectives To determine the correlation and accuracy of a CGMS to monitor neonatal foals' blood glucose concentrations as compared to a POC glucometer and laboratory chemistry analysis (CHEM). Animals Samples from 4 healthy and 4 ill neonatal foals. Methods A CGMS was placed on each foal, and glucose measurements acquired from this device were compared to simultaneous measurements of blood glucose concentration using a POC glucometer and CHEM. Results Two‐hundred matched glucose measurements were collected from 8 neonatal foals. The mean bias (95% limits of agreement) between CGMS and CHEM, CGMS and POC glucometer, and POC glucometer and CHEM was 3.97 mg/dL (−32.5 to 40.4), 18.2 mg/dL (−28.8 to 65.2), and 22.18 mg/dL (−9.3 to 53.67), respectively. The Pearson's correlation coefficient (r) was significantly correlated among all devices: GCMS and CHEM (r = 0.81), CGMS and POC glucometer (r = 0.77) and POC glucometer‐CHEM (r = 0.92). Conclusions and Clinical Importance Within the blood glucose concentration ranges in this study (78‐212 mg/dL), CGMS measurements were significantly correlated with CHEM, suggesting that it is an acceptable method to provide meaningful, immediate, and continuous glucose concentration measurements in neonatal foals while eliminating the need for repeated restraint and blood collection.

In the 20th century, Peru was one of the major fishmeal producers worldwide. Luis Banchero Rossi (1929-1972) was the main driving force behind this economic boom. This article discusses how, given a set of historical conditions favoring such a setting, Banchero’s business performance surpassed that of other Peruvian and foreign producers in the industry, and enabled this development. This research uses complementary methodologies; i.e., case study work and financial databases. The authors find that Banchero’s share in Peru’s total exports reached 15.3 % in 1968, far above the next largest Peruvian exporter. In this regard, Banchero operated his organization following a set of criteria, called market governance by Williamson, plus several advantages, including negotiation abilities, social capital formation, human capital management, and tacit knowledge development, building on Peru’s specific sociological conditions. These conclusions help understanding how an entrepreneur of humble origins like Banchero worked around a commodity such as fishmeal to become a successful business leader worldwide.

Introduction The REFORM (REhabilitation FOR Musculoskeletal conditions) trial is a non-inferiority randomised controlled trial (n=210) designed to determine whether a supported home exercise programme is as good or better than a course of face-to-face physiotherapy for the management of some musculoskeletal conditions. The trial is currently being conducted across Sydney government hospitals in Australia. This process evaluation will run alongside the REFORM trial. It combines qualitative and quantitative data to help explain the trial results and determine the feasibility of rolling out supported home exercise programmes in settings similar to the REFORM trial.Methods and analysis Two theoretical frameworks underpin our process evaluation methodology: the Realist framework (context, mechanism, outcomes) considers the causal assumptions as to why a supported home exercise programme may be as good or better than face-to-face physiotherapy in terms of the context, mechanisms and outcomes of the trial. The RE-AIM framework describes the Reach, Effectiveness, Adoption, Implementation and Maintenance of the intervention. These two frameworks will be broadly used to guide this process evaluation using a mixed-methods approach. For example, qualitative data will be derived from interviews with patients, healthcare professionals and stakeholders, and quantitative data will be collected to determine the cost and feasibility of providing supported home exercise programmes. These data will be analysed iteratively before the analysis of the trial results and will be triangulated with the results of the primary and secondary outcomes.Ethics and dissemination This trial will be conducted in accordance with the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2018) and the Note for Good Clinical Practice (CPMP/ICH-135/95). Ethical approval was obtained on 17 March 2017 from the Northern Sydney Local Health District Human Research Ethics Committee (trial number: HREC/16HAWKE/431-RESP/16/287) with an amendment for the process evaluation approved on 4 February 2020. The results of the process evaluation will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.Trial registration number ACTRN12619000065190.

Background & Aims: HDV affects 4.5–13% of chronic hepatitis B (CHB) patients globally, yet the prevalence of HDV infection in Canada is unknown. To investigate the prevalence, genotype, demographics, and clinical characteristics of HDV in Canada, we conducted a retrospective analysis of (1) HDV antibody and RNA positivity among referred specimens, and (2) a cross-sectional subset study of 135 HDV seropositive +/-RNA (HDV+) patients compared with 5,132 HBV mono-infected patients in the Canadian HBV Network. Methods: Anti-HDV IgG-positive specimens collected between 2012 and 2019 were RNA tested and the genotype determined. Patients enrolled in the Canadian HBV Network were >18 years of age and HBsAg-positive. Clinical data collected included risk factors, demographics, comorbidities, treatment, fibrosis assessment, and hepatic complications. Results: Of the referred patients, 338/7,080 (4.8%, 95% CI 4.3–5.3) were HDV seropositive, with 219/338 RNA-positive (64.8%, 95% CI 59.6–69.7). The HDV+ cohort were more likely to be born in Canada, to be White or Black/African/Caribbean than Asian, and reporting high-risk behaviours, compared with HBV mono-infected patients. Cirrhosis, complications of end-stage liver disease, and liver transplantation were significantly more frequent in the HDV+ cohort. HDV viraemia was significantly associated with elevated liver transaminases and cirrhosis. Five HDV genotypes were observed among referred patients but no association between genotype and clinical outcome was detected within the HDV+ cohort. Conclusions: Nearly 5% of the Canadian HBV referral population is HDV seropositive. HDV infection is highly associated with risk behaviours and both domestic and foreign-born patients with CHB. HDV was significantly associated with progressive liver disease highlighting the need for increased screening and surveillance of HDV in Canada. Lay summary: Evidence of HDV infection was observed in approximately 5% of Canadians who were infected with HBV referred to medical specialists. HDV-positive patients were more likely to be male, born in Canada, or White or Black/African/Caribbean compared to Asian, and to have reported high-risk activities such as injection or intranasal drug use or high-risk sexual contact compared with patients infected with only HBV. Patients infected with HDV were also more likely to suffer severe liver disease, including liver cancer, compared with HBV mono-infected patients.

The sudden outbreak of the Coronavirus disease (COVID-19) swept across the world in early 2020, triggering the lockdowns of several billion people across many countries, including China, Spain, India, the U.K., Italy, France, Germany, Brazil, Russia, and the U.S. The transmission of the virus accelerated rapidly with the most confirmed cases in the U.S., India, Russia, and Brazil. In response to this national and global emergency, the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implementation strategies to rapidly respond to this crisis, for supporting research, saving lives, and protecting the health of global citizens. This perspective paper presents our collective view on the global health emergency and our effort in collecting, analyzing, and sharing relevant data on global policy and government responses, human mobility, environmental impact, socioeconomical impact; in developing research capabilities and mitigation measures with global scientists, promoting collaborative research on outbreak dynamics, and reflecting on the dynamic responses from human societies.

Introduction and objectives: The prevalence of alcohol, tobacco, and coffee use and association with liver health among North Americans with Chronic Hepatitis B (CHB) infection has not been well described. Materials and methods: The Hepatitis B Research Network includes an observational study of untreated CHB adults enrolled at 21 sites in the United States and Canada. Alcohol use was categorized as none, moderate, and at-risk based on the definition from the National Institute on Alcohol Abuse and Alcoholism; tobacco use as never, current and former; coffee use as none, 1–2 cups/day, and ≥3 cups/day. Linear regression and linear mixed models were used to associate lifestyle behaviors with ALT and FIB-4 values. Results: 1330 participants met eligibility: 53% males, 71% Asian and the median age was 42 years (IQR: 34–52). Median ALT was 33 U/L (IQR: 22–50), 37% had HBV DNA

Background: Pain is a significant problem in adults living with advanced liver disease, having limited guidance available for its clinical management. While pain is considered a multidimensional experience, there have been limited reviews of the pain literature in advanced liver disease conducted with a multidimensional framework. Aims: The goal of this scoping review was to identify and map the multidimensional domains of pain in adults with advanced liver disease using the biopsychosocial model. Methods: We used Arksey and O’Malley’s scoping framework. A search was conducted in MEDLINE, Embase, AMED, and CINAHL databases and the gray literature using specific eligibility criteria (1990–2019). Citation selection and data extraction were performed by two independent reviewers and in duplicate. Results: Of the 43 studies that met inclusion criteria, 51% were from North America and 93% utilized quantitative methods. The combined studies reported on 168,110 participants with ages ranging between 23 to 87 years. Only 9% reported an objective scoring system for liver disease severity. Few studies reported pain classification (9%) and intensity (16%). Pain prevalence ranged between 18% and 100%, with pain locations including joint, abdomen, back, head/neck, and upper/lower extremities. We identified and mapped 115 pain factors to the biopsychosocial model: physical (81%), psychological (65%), and sociocultural (5%). Only 9% measured pain using validated multidimensional tools. Pharmacological intervention (92%) prevailed among pain treatments. Conclusions: Pain is not well understood in patients with advanced liver disease, having limited multidimensional pain assessment and treatment approaches. There is a need to systematically examine the multidimensional nature of pain in this population.

Automated vehicle technology has recently become reliant on 3D LiDAR sensing for perception tasks such as mapping, localization and object detection. This has led to a rapid growth in the LiDAR manufacturing industry with several competing makers releasing new sensors regularly. With this increased variety of LiDARs, each with different properties such as number of laser emitters, resolution, field-of-view, and price tags, a more in-depth comparison of their characteristics and performance is required. This work compares 10 commonly used 3D LiDARs, establishing several metrics to assess their performance. Various outstanding issues with specific LiDARs were qualitatively identified. The accuracy and precision of individual LiDAR beams and accumulated point clouds are evaluated in a controlled environment at distances from 5 to 180 meters. Reflective targets were used to characterize intensity patterns and quantify the impact of surface reflectivity on accuracy and precision. A vehicle and pedestrian mannequin were also used as additional targets of interest. A thorough assessment of these LiDARs is given with their potential applicability for automated driving tasks. The data collected in these experiments and analysis tools are all shared openly.

Introduction Exercise, support and advice are considered core components of management for most musculoskeletal conditions and are typically provided by physiotherapists through regular face-to-face treatments. However, exercise can be provided remotely as part of a home exercise programme, while support and advice can be provided over the telephone. There is initial evidence from trials and systematic reviews to suggest that remotely provided physiotherapy can be used to manage a variety of musculoskeletal conditions safely and effectively.Methods and analysis The aim of this single-blind randomised controlled non-inferiority trial is to determine whether a supported home exercise programme is as good as or better than face-to-face physiotherapy for the treatment of musculoskeletal conditions. Two hundred and ten participants will be recruited from five public hospitals in Sydney, Australia. Participants will be randomised to either the supported home exercise group or the face-to-face physiotherapy group. Participants allocated to the supported home exercise group will initially receive one face-to-face session with the trial physiotherapist and will then be managed remotely for the next 6 weeks. Participants allocated to the face-to-face physiotherapy group will receive a course of physiotherapy as typically provided in Sydney government hospitals. The primary outcome is function measured by the Patient Specific Functional Scale at 6 weeks. There will be nine secondary outcomes measured at 6 and 26 weeks. Separate analyses will be conducted on each outcome, and all analyses will be conducted on an intention-to-treat basis. A health economic evaluation will be conducted from a health funder plus patient perspective.Ethics and dissemination Ethical approval was obtained on the 17 March 2017 from the Northern Sydney Local Health District HREC, trial number HREC/16HAWKE/431-RESP/16/287. The results of this study will be submitted for publication to peer-reviewed journals and be presented at national and international conferences. Recruitment commenced in March 2019, and it is anticipated that the trial will be completed by December 2021. This trial will investigate two different models of physiotherapy care for people with musculoskeletal conditions.Trial registration number CPMP/ICH-135/95.Protocol version The most recent version of the protocol is V.1.2 dated November 2019.

Eccrine spiradenoma is a benign adnexal tumor of the sweat gland. Giant vascular eccrine spiradenoma is a rare variant of eccrine spiradenoma, characterized by its large size and florid vascularity. Its rarity and clinical appearance give rise to typical misdiagnosis as angiomatous lesions. We present a case of a giant vascular eccrine spiradenoma that was initially diagnosed as a thrombosed varix on the basis of clinical presentation and ultrasound features. This case reintroduces this rare condition and also highlights the differential diagnoses of lower limb skin nodules that may masquerade as a thrombosed varix. Keywords: Eccrine spiradenoma, Thrombosed varix, Varicose vein, Thrombosis

This article studies with a business history framework the history of immigrant entrepreneurship of a North American family in Peru, whose origin goes back to the second half of the nineteenth century and its development takes place in the first forty years of the twentieth century. The origins go back to Ernesto Thorndike, a North American businessman whose business trajectory was situated principally in Peru. At the end of his life, he saw the decline of his fortune despite his social and intellectual capital, of being part of the economic and social elite of Lima at the end of the nineteenth century and the beginnings of the twentieth, and of the diversification of its businesses. The article analyzes this evolution and indicates driving factors of success and decline: intellectual capital un-exploitable because of Peru´s political and economic instability (the construction of railroads was paralyzed at the end of nineteenth century); the lack of speed to produce the necessary tacit technical knowledge to diversify of its businesses; and the lack of bonding social capital, which prevented the constitution of a family business group that capitalized contacts and relationships that extends in time the existence of firms beyond a generation.

Summary: Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced by BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress inflammation by targeting NF-κB and TNF-α signaling and foster M2 polarization in recipient macrophages. Repeated infusions of BMDM-IL-4-exo into Apoe−/− mice fed a Western diet reduce excessive hematopoiesis in the bone marrow and thereby the number of myeloid cells in the circulation and macrophages in aortic root lesions. This also leads to a reduction in necrotic lesion areas that collectively stabilize atheroma. Thus, BMDM-IL-4-exo may represent a useful therapeutic approach for atherosclerosis and other inflammatory disorders by targeting NF-κB and TNF-α via microRNA cargo delivery.

Objectives National guidelines for identifying physiological deterioration and sepsis in hospitals depend on thresholds for blood pressure that do not account for age or sex. In populations outside hospital, differences in blood pressure are known to occur with both variables. Whether these differences remain in the hospitalised population is unknown. This database analysis study aims to generate representative centiles to quantify variations in blood pressure by age and sex in hospitalised patients.Design Retrospective cross-sectional observational database analysis.Setting Four near-sea-level hospitals between April 2015 and April 2017Participants 75 342 adult patients who were admitted to the hospitals and had at least one set of documented vital sign observations within 24 hours before discharge were eligible for inclusion. Patients were excluded if they died in hospital, had no vital signs 24 hours prior to discharge, were readmitted within 7 days of discharge, had missing age or sex or had no blood pressure recorded.Results Systolic blood pressure (SBP) for hospitalised patients increases with age for both sexes. Median SBP increases from 122 (CI: 121.1 to 122.1) mm Hg to 132 (CI: 130.9 to 132.2) mm Hg in men, and 114 (CI: 113.1 to 114.4) mm Hg to 135 (CI: 134.5 to 136.2) mm Hg in women, between the ages of 20 and 90 years. Diastolic blood pressure peaked around 50 years for men 76 (CI: 75.5 to 75.9) mm Hg and women 69 (CI: 69.0 to 69.4) mm Hg. The blood pressure criterion for sepsis, systolic

Introduction: Patients with trauma-induced coagulopathies may benefit from the use of antifibrinolytic agents, such as tranexamic acid (TXA). This study evaluated the safety and efficacy of TXA in civilian adults hospitalized with traumatic hemorrhagic shock. Methods: Patients who sustained blunt or penetrating trauma with signs of hemorrhagic shock from June 2014 through July 2018 were considered for TXA treatment. A retrospective control group was formed from patients seen in the same past five years who were not administered TXA and matched based on age, gender, Injury Severity Score (ISS), and mechanism of injury (blunt vs penetrating trauma). The primary outcome of this study was mortality measured at 24 hours, 48 hours, and 28 days. Secondary outcomes included total blood products transfused, hospital length of stay (LOS), intensive care unit LOS, and adverse events. We conducted three pre-specified subgroup analyses to assess outcomes of patients, including (1) those who were severely injured (ISS >15), (2) those who sustained significant blood loss (≥10 units of total blood products transfused), and (3) those who sustained blunt vs penetrating trauma. Results: Propensity matching yielded two cohorts: the hospital TXA group (n = 280) and a control group (n = 280). The hospital TXA group had statistically lower mortality at 28 days (1.1% vs 5%, odds ratio [OR] [0.21], (95% confidence interval [CI], 0.06, 0.72)) and used fewer units of blood products (median = 4 units, interquartile range (IQR) = [1, 10] vs median=7 units, IQR = [2, 12.5] for the hospital TXA and control groups, respectively, (95% CI for the difference in median, -3 to -1). There were no statistically significant differences between groups with regard to 24-hour mortality (1.1% vs 1.1%, OR = 1, 95% CI, 0.20, 5.00), 48-hour mortality (1.1% vs 1.4%, OR [0.74], 95% CI, 0.17, 3.37), hospital LOS (median= 9 days, IQR = (5, 16) vs median =12 days IQR = (6, 22.5) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (−5 to 0)), and incidence of thromboembolic events (eg, deep vein thrombosis, pulmonary embolism) during hospital stay (0.7% vs 0.7% for the hospital TXA and control group, respectively, OR [1], 95% CI, 0.14 to 7.15). We conducted subgroup analyses on patients with ISS>15, patients transfused with ≥10 units of blood products, and blunt vs penetrating trauma. The results indicated lower 28-day mortality for ISS>15 (1.8% vs 7.1%, OR [0.23], 95% CI, 0.06 to 0.81) and blunt trauma (0.6% vs 6.3%, OR [0.09], 95% CI, 0.01 to 0.75); fewer units of blood products for penetrating trauma (median = 2 units, IQR = (1, 8) vs median = 8 units, IQR = (5, 15) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (−6 to −3)), and ISS>15 (median = 7 units, IQR = (2, 14) vs median = 8.5 units, IQR = (4, 16) for the hospital TXA and control groups, respectively, 95% CI for the difference in median, −3 to 0). Conclusion: The current study demonstrates a statistically significant reduction in mortality after TXA administration at 28 days, but not at 24 and 48 hours, in patients with traumatic hemorrhagic shock.

Carbon dioxide can interact with proteins to form carbamate post-translational modifications. Here, the authors developed a strategy to identify carbamate post-translational modifications by trapping carbon dioxide and subsequently identifying the carbamylated proteins.

Abstract Background This study investigates the impact of methamphetamine use on trauma patient outcomes. Methods This retrospective study analyzed patients between 18 and 55 years old presenting to a single trauma center in San Bernardino County, CA who sustained traumatic injury during the 10-year study period (January 1st, 2005 to December 31st, 2015). Routine serum ethanol levels and urine drug screens (UDS) were completed on all trauma patients. Exclusion criteria included patients with an elevated serum ethanol level (> 0 mg/dL). Those who screened positive on UDS for only methamphetamine and negative for cocaine and cannabis (MA(+)) were compared to those with a triple negative UDS for methamphetamine, cocaine, and cannabis (MA(−)). The primary outcome studied was the impact of a methamphetamine positive drug screen on hospital mortality. Secondary outcomes included length of stay (LOS), heart rate, systolic and diastolic blood pressure (SBP and DBP, respectively), and total amount of blood products utilized during hospitalization. To analyze the effect of methamphetamine, age, gender, injury severity score, and mechanism of injury (blunt vs. penetrating) were matched between MA(−) and MA(+) through a propensity matching algorithm. Results After exclusion, 2538 patients were included in the final analysis; 449 were patients in the MA(+) group and 2089 patients in the MA(−) group. A selection of 449 MA(−) patients were matched with the MA(+) group based on age, gender, injury severity score, and mechanism of injury. This led to a final sample size of 898 patients with 449 patients in each group. No statistically significant change was observed in hospital mortality. Notably, a methamphetamine positive drug screen was associated with a longer LOS (median of 4 vs. 3 days in MA(+) and MA(−), respectively, p

Why do some small companies in the clothing industry fail to grow while others succeed is the conundrum that this study sets out to solve. It does so by identifying and explaining four cases of enterprises with varying performance levels. On the understanding that there are structural and historical conditions that correspond to trends, these cases are explained and the question is answered. Based on the evidence, the article finds that the prevailing inequality is due to the greater or lesser presence of social capital - resources that come from networks and which are accessed through relationships - and to institutional and structural conditions that slow growth. Added to this are the differing responses of enterprises to the negative effects of poor-quality institutions. Following the approach of Nahapiet and Ghoshal, the study explains how an actor can develop certain range of capacities for participating in networks, before stalling as a result of a diversity of conditions.

Introduction: Radiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepa-tocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death. Material and methods: We conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes. Results: 219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001). Conclusion: Incremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.

In response to an insufficiently skilled labour force, Arab countries are looking to Western adult learning perspectives. However, Western practices cannot be implemented without consideration of regional culture. This large-scale study aims to identify best leadership development practices for Arab adult learners and examines how these practices might best fit with local cultural contexts. To determine effective practices for Arab leaders, the Delphi process was utilised to survey 24 experts in the field of executive education. In addition, eight experts were interviewed and 1,500 business leaders from 17 different countries were surveyed. Hierarchical Linear Modelling (HLM) was used to examine indices for individual level relationships, as well as country level relationships. Findings suggest that adult learning practices must be ‘customised’ to address the tension between global and local perspectives. Previous experiences of Western practices are equally important. Traditional schooling experiences may foster deep resistance to unfamiliar ideas and practices.

TPE has a role in the management of various immune-mediated neurological disorders including CNS inflammatory demyelinating disorders (CNS-IDD), often as second line treatment following high dose steroids in part due to perceived risk, which inevitably result in delays in accessing TPE. There has been limited evidence such delays impact long-term outcome, however emerging data suggests that even 10-14 days, typical of when TPE is reserved for steroid-unresponsive patients, may adversely affect outcomes. We review TPE use in CNS-IDD, focusing on emerging data on timing and implications for clinical practice.

Introduction: Hemorrhage is one of the leading causes of death in trauma victims. Historically, paramedics have not had access to medications that specifically target the reversal of trauma-induced coagulopathies. The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to evaluate the safety and efficacy of tranexamic acid (TXA) use in the civilian prehospital setting in cases of traumatic hemorrhagic shock. Methods: The Cal-PAT study is a multi-centered, prospective, observational cohort study with a retrospective comparison. From March 2015 to July 2017, patients ≥ 18 years-old who sustained blunt or penetrating trauma with signs of hemorrhagic shock identified by first responders in the prehospital setting were considered for TXA treatment. A control group was formed of patients seen in the five years prior to data collection cessation (June 2012 to July 2017) at each receiving center who were not administered TXA. Control group patients were selected through propensity score matching based on gender, age, Injury Severity Scores, and mechanism of injury. The primary outcome assessed was mortality recorded at 24 hours, 48 hours, and 28 days. Additional variables assessed included total blood products transfused, the hospital and intensive care unit length of stay, systolic blood pressure taken prior to TXA administration, Glasgow Coma Score observed prior to TXA administration, and the incidence of known adverse events associated with TXA administration. Results: We included 724 patients in the final analysis, with 362 patients in the TXA group and 362 in the control group. Reduced mortality was noted at 28 days in the TXA group in comparison to the control group (3.6% vs. 8.3% for TXA and control, respectively, odds ratio [OR]=0.41 with 95% confidence interval [CI] [0.21 to 0.8]). This mortality difference was greatest in severely injured patients with ISS >15 (6% vs 14.5% for TXA and control, respectively, OR=0.37 with 95% CI [0.17 to 0.8]). Furthermore, a significant reduction in total blood product transfused was observed after TXA administration in the total cohort as well as in severely injured patients. No significant increase in known adverse events following TXA administration were observed. Conclusion: Findings from the Cal-PAT study suggest that TXA use in the civilian prehospital setting may safely improve survival outcomes in patients who have sustained traumatic injury with signs of hemorrhagic shock.

Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

Background A thorough history and physical examination in patients with blunt abdominal trauma (BAT) is important to safely exclude clinically significant intra-abdominal injury (IAI). We seek to evaluate a correlation between self-reported abdominal pain, abdominal tenderness on examination and IAI discovered on CT or during exploratory laparotomy.Methods This retrospective analysis assessed patients with BAT ≥13 years old who arrived to the emergency department following BAT during the 23-month study period. Upon arrival, the trauma team examined all patients. Only those who underwent an abdominal and pelvic CT scan were included. Patients were excluded if they were unable to communicate or lacked documentation, had obvious evidence of extra-abdominal distracting injuries, had a positive drug or alcohol screen, had a Glasgow Coma Scale ≤13, or had a positive pregnancy screening. The primary objective was to assess the agreement between self-reported abdominal pain and abdominal tenderness on examination and IAI noted on CT or during exploratory laparotomy.Results Among the 594 patients included in the final analysis, 73.1% (n=434) had no self-reported abdominal pain, 64.0% (n=384) had no abdominal tenderness on examination, and 22.2% (n=132) had positive CT findings suggestive of IAI. Among the 352 patients who had no self-reported abdominal pain and no abdominal tenderness on examination, a significant number of positive CT scan results (14%, n=50) were still recorded. Furthermore, a small but clinically significant portion of these 50 patients underwent exploratory laparotomy (1.1%, n=4). All four of these patients ultimately underwent a splenectomy and all were completed on hospital day one.Conclusion Lack of abdominal pain and tenderness in patients with BAT with non-distracting injuries was associated with a small portion of patients who underwent a splenectomy. Patients with BAT without abdominal pain or tenderness may need a period of observation or CT scan to rule out IAI prior to discharge home.Level of evidence Level III, therapeutic/care management.

Introduction: The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to assess the safety and impact on patient mortality of tranexamic acid (TXA) administration in cases of trauma-induced hemorrhagic shock. The current study further aimed to assess the feasibility of prehospital TXA administration by paramedics within the framework of North American emergency medicine standards and protocols. Methods: This is an ongoing multi-centered, prospective, observational cohort study with a retrospective chart-review comparison. Trauma patients identified in the prehospital setting with signs of hemorrhagic shock by first responders were administered one gram of TXA followed by an optional second one-gram dose upon arrival to the hospital, if the patient still met inclusion criteria. Patients administered TXA make up the prehospital intervention group. Control group patients met the same inclusion criteria as TXA candidates and were matched with the prehospital intervention patients based on mechanism of injury, injury severity score, and age. The primary outcomes were mortality, measured at 24 hours, 48 hours, and 28 days. Secondary outcomes measured included the total blood products transfused and any known adverse events associated with TXA administration. Results: We included 128 patients in the prehospital intervention group and 125 in the control group. Although not statistically significant, the prehospital intervention group trended toward a lower 24-hour mortality rate (3.9% vs 7.2% for intervention and control, respectively, p=0.25), 48-hour mortality rate (6.3% vs 7.2% for intervention and control, respectively, p=0.76), and 28-day mortality rate (6.3% vs 10.4% for intervention and control, respectively, p=0.23). There was no significant difference observed in known adverse events associated with TXA administration in the prehospital intervention group and control group. A reduction in total blood product usage was observed following the administration of TXA (control: 6.95 units; intervention: 4.09 units; p=0.01). Conclusion: Preliminary evidence from the Cal-PAT study suggests that TXA administration may be safe in the prehospital setting with no significant change in adverse events observed and an associated decreased use of blood products in cases of trauma-induced hemorrhagic shock. Given the current sample size, a statistically significant decrease in mortality was not observed. Additionally, this study demonstrates that it may be feasible for paramedics to identify and safely administer TXA in the prehospital setting.

Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient’s partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk.

The prevalence of obesity has increased dramatically in recent decades. It is an important public health issue as it causes many other chronic health conditions, such as hypertension, cardiovascular diseases, and type II diabetics. Obesity affects life expectancy and even the quality of lives. Eventually, it increases social costs in many ways due to increasing costs of health care and workplace absenteeism. Using the spatial patterns of obesity prevalence as an example; we show how different geographic units can reveal different degrees of detail in results of analysis. We used both census tracts and census block groups as units of geographic analysis. In addition; to reveal how different geographic scales may impact on the analytic results; we applied geographically weighted regression to model the relationships between obesity rates (dependent variable) and three independent variables; including education attainment; unemployment rates; and median family income. Though not including an exhaustive list of explanatory variables; this regression model provides an example for revealing the impacts of geographic scales on analysis of health data. With obesity data based on reported heights and weights on driver’s licenses in Summit County, Ohio, we demonstrated that geographically weighted regression reveals varying spatial trends between dependent and independent variables that conventional regression models such as ordinary least squares regression cannot. Most importantly, analyses carried out with different geographic scales do show very different results. With these findings, we suggest that, while possible, smaller geographic units be used to allow better understanding of the studies phenomena.

In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p

It is well appreciated that ethnicity influences the natural history and immune responses during a chronic hepatitis B infection. In this study, we explore the effect of ethnicity and treatment cessation on Hepatitis B surface Antigen (HBsAg) seroclearance in patients with Nucleos(t)ide Analogue (NA)-induced Hepatitis B e Antigen (HBeAg) seroconversion. We performed a multi-ethnic, multicentric observational cohort study. The analyzed cohort consisted of 178 mono-infected, predominantly male (75.3%) chronic hepatitis B patients of mixed ethnicity (44.4% Asians, 48.9% Caucasians) with nucleos(t)ide analogue-induced HBeAg seroconversion. Treatment was withdrawn in 105 patients and continued in 73, leading to HBsAg loss in 14 patients off- and 16 patients on-treatment, respectively. Overall, HBsAg loss rates were not affected by treatment cessation (hazard ratio 1.45, p = 0.372), regardless of consolidation treatment duration. Caucasian ethnicity was associated with an increased chance of HBsAg loss (hazard ratio 6.70, p = 0.001), but hepatitis B virus genotype was not (p = 0.812). In conclusion, ethnicity is the most important determinant for HBsAg loss after NA-induced HBeAg seroconversion, with up to six-fold higher HBsAg loss rates in Caucasians compared to Asians, irrespective of treatment cessation and consolidation treatment duration.

Botulinum neurotoxins (BoNT) are potential biothreat agents due to their high lethality, potency, and ease of distribution, thus the development of antitoxins is a high priority to the US government. This study examined pre-clinical pharmacokinetic studies in rats of four oligoclonal anti-BoNT mAb-based therapeutics (NTM-1631, NTM-1632, NTM-1633, NTM-1634) for five BoNT serotypes (A, B, E, C, and D). NTM-1631, NTM-1632, and NTM-1633 each consist of three IgG1 mAbs, each with a distinct human or humanized variable region which bind to distinct epitopes on BoNT serotype A, B, or E respectively. NTM-1634 consists of four human immunoglobulin G1 (IgG1) mAbs binding BoNT C/D mosaic toxins. The mechanism of these antitoxins requires that three antibodies simultaneously bind toxin to achieve rapid clearance. Rats (total 378) displayed no adverse clinical signs attributed to antibody treatment from any of the antitoxins. Pharmacokinetic evaluation demonstrated that the individual mAbs are slowly eliminated, exhibiting dose-dependent exposure and long elimination half-lives ranging from 6.5 days to 10 days. There were no consistent differences observed between males and females or among the individual antibodies in each formulation in half-life. Anti-drug antibodies (ADA) were observed, as expected for human antibodies administered to rats. The results presented were used to support the clinical investigation of antibody-based botulism antitoxins.

Introduction: Stroke is one of the leading causes of death worldwide. Protective agents that could diminish the injuries induced by cerebral ischemia/reperfusion (I/R) are crucial to alleviate the detrimental outcome of stroke. The aim of this study is to investigate the protective roles of lutein in cerebral I/R injury. Methods: Two-hour cerebral ischemia was induced by unilateral middle cerebral artery occlusion (MCAo) in mice. Either lutein (0.2 mg/kg) or vehicle was given to mice intraperitoneally 1 h after MCAo and 1 h after reperfusion. Neurological deficits were evaluated at 22 h after reperfusion while survival rate was assessed daily until 7 days after reperfusion. Brains were cut into 2 mm-thick coronal slices and stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct size after MCAo. Paraffin-embedded brain sections were prepared for TUNEL assay and immunohistochemistry. Protein lysate was collected for Western blotting experiments. Results: Higher survival rate, better neurological scores, smaller infarct area and smaller infarct volume were noted in the lutein-treated group. Immunohistochemistry data showed a decrease of immunoreactivity of nitrotyrosine, poly(ADP-ribose) and NFκB in the lutein-treated brains. Western blotting data showed decreased levels of Cox-2, pERK, and pIκB, but increased levels of Bcl-2, heat shock protein 70 and pAkt in the lutein-treated brains. Conclusions: Post-treatment of lutein protected the brain from I/R injury, probably by its anti-apoptotic, anti-oxidative and anti-inflammatory properties. These suggest that lutein could diminish the deleterious outcomes of cerebral I/R and may be used as a potential treatment for stroke patients.

Aims : To report a prospective non-comparative consecutive interventional study on the safety and efficacy of 23-Gauge transconjunctival sutureless pars plana vitrectomy for primary rhegmatogenous retinal detachment (RRD). Materials and Methods: Fifty eyes of 50 consecutive patients were recruited between June 2007 and January 2008. All surgeries were performed using the one-step 23-Gauge system with angled incisions. The surgical protocol consisted of a minimum of eight clinical visits: baseline, 1 day, 1 week, 1-, 3- and 6- months after the initial surgery. The endpoints were anatomical, functional results and complications arising from the surgery. Results : Anatomical success was achieved in 82% of cases (41 out of 50) with single surgery and rose to 98% (49 out of 50) with additional surgery. Mean visual acuity improved from logMAR 0.48(SD 0.36) to 0.26(SD 0.31), P < 0.001. Two cases with ocular hypotony, defined as an intraocular pressure ≤ 6mmHg, that were associated with a choroidal detachment were seen. Conclusions : Acceptable anatomical and functional success rates can be achieved with primary 23-Gauge transconjunctival sutureless vitrectomy for RRD. We found that the approach technique is different from conventional vitrectomy and the complications arising from post surgical hypotony and leakage from sclerotomies are potentially higher compared to 20-Gauge vitrectomy.