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Screening of Blood Parasites in Australian Wild Deer
Jose Huaman
Carlo Pacioni

Jose Huaman

and 6 more

May 13, 2020
Wild animals are natural reservoir hosts for a variety of pathogens, and such is the case for deer (family Cervidae). Deer were introduced to Australia 150 years ago for farming and game, but wild deer populations have expanded considerably in recent years, posing increasing threats to biodiversity, agriculture and public health. There are few data currently available on pathogens that Australian wild deer carry or whether these organisms pose biosecurity threats to humans, wildlife, livestock or other domestic animals. To address this knowledge gap, we tested for the presence of seven parasitic genera in 243 blood samples collected from four wild deer species in eastern Australia. Blood samples were tested by PCR for the presence of Plasmodium, Trypanosoma, Babesia, Theileria, Toxoplasma, Sarcocystis and Neospora DNA. No amplification was obtained for either the 18S rRNA (or the cytochrome b gene in the case of Plasmodium) of the seven selected parasitic genera, suggesting that wild deer in eastern Australia currently pose little risk as vectors of these parasites to livestock and humans. This survey represents the first molecular study of its type in Australian deer and provides important baseline information about the health status of these animals.
Active agents of Renin Angiotensin System and SARS-CoV-2
Antonio Vitiello
Raffaele La Porta

Antonio Vitiello

and 4 more

May 13, 2020
Introduction The new coronavirus, called SARS-CoV-2, is responsible for the recent outbreak of serious respiratory diseases worldwide. The state of the global pandemic is still being declared and the virus has already claimed thousands of victims. Therapies are urgently needed to contain its rapid spread and reduce high mortality rates, no direct antiviral is yet available and several clinical trials are underway. In addition, no vaccines are currently available and any development in this direction may take several months. Experts in the field have divided SARS-Cov-2 infection into three phases. Materials and methods This article explores the scientific hypothesis based on pharmacological and molecular knowledge to consider drugs that modulate the RAS system as therapeutic agents that can help the body fight SARS-CoV-2 infection. Results It is known from the 2003 SARS epidemic that the critical receptor for SARS-CoV entry into host cells is the angiotensin 2 conversion enzyme (ACE2), the strain involved in the current SARS-CoV-2 epidemic is similar to the SARS-CoV variety involved in the 2002-2003 SARS epidemic. ACE-2 is part of the RAS system, modulating this enzyme could be effective. Conclusions A scientific hypothesis is described, in the absence of studies and clinical data, based on therapeutic treatments that modulate RAS, and current knowledge of the mechanism of penetration of SARS-CoV-2 into cells, and the role of ACE-2 in the inflammatory state of the infection.
Pneumopericardium causing pericardial tamponade
Ryan Fink

Ryan Fink

May 13, 2020
Pneumopericardium, or gas in the pericardial sac, is a rare condition that typically presents with chest pain or pericarditis, but can be severe enough to cause tamponade physiology. The images presented show the typical appearance of pneumopericardium. This patient had tamponade physiology requiring a pericardial drain in the operating room.
Development of Bing-Neel syndrome Despite Ibrutinib Therapy for Waldenstrom Macroglob...
Lukas Delasos
Deep Phachu

Lukas Delasos

and 4 more

May 13, 2020
Bing-Neel syndrome (BNS) remains a rare complication of Waldenstrom Macroglobulinemia. Given the paucity of this disease, treatment guidelines are based on small clinical trials with limited participants. Here we present a case of BNS that developed while on ibrutinib therapy, followed by a review of the next steps in management.
Adaptation of the IDF WINGS programme for Hyperglycaemia in Pregnancy in Guyana, Sout...
Julia Lowe
Brian Ostrow

Julia Lowe

and 7 more

May 13, 2020
Objective: Introduced of a protocol for the outpatient management of hyperglycaemia in pregnancy (HIP) in Guyana based on the IDF WINGS programme Design: Quality improvement programme and education intervention Setting: The national referral hospital in Georgetown (GPHC) and two associated community health centres (HC). Population: Pregnant women of <37weeks gestational age. Methods: An inter-professional team of clinical leaders introduced universal screening for gestational diabetes (GDM)using a 75gm OGTT and simplified outpatient management of HIP with self-monitoring of blood glucose, diet followed by metformin then insulin. Main Outcome Measures: Numbers of women screened, diagnosed and treated for HIP. Results: Between November 2016 and 1st July 2019, 2226 pregnant women were screened, 461 25.9%) were abnormal at GPHC and 12 (2.6%) at the HC. Forty-four% were treated with medical nutritional therapy alone, 43% required metformin and 13% received insulin. Caesarian section rates were high (46%) and attendance for postpartum OGTT poor (15%). Conclusions: The high rate of positive tests at GPHC is consistent with the system of transferring high risk patients to GPHC. Before supporting a nationwide universal screening programme, further investigation is required, eg screening for GDM at regional hospitals and HC outside the immediate GPHC catchment. Our results suggest universal screening may not be the only choice for the populations of low-and-middle income countries. Funding: World Diabetes Foundation (WDF) and the Banting and Best Diabetes Centre (BBDC) of the University of Toronto. Keywords: Hyperglycaemia in pregnancy, diabetes, oral glucose tolerance test.
Single-incision Laparoscopic Surgery for Removal of Ectopic IUD with Bladder Repair
Hanlin Yang
Kristina Duan

Hanlin Yang

and 5 more

May 13, 2020
Objective: To investigate the advantages of using single-incision laparoscopy in the removal of ectopic IUD and bladder repair surgery. Patient: An asymptomatic 42-year-old woman with an 18-year IUD history requested removal of her IUD with a desire to conceive in the near future. Ultrasound and X-ray imaging identified the device penetrating completely through the uterus and partially through the bladder. The IUD was removed via single- incision laparoscopic surgery and hysteroscopy after the patient expressed concern for the cosmetic aftermath of multi-port surgery. Outcome: An ectopic IUD removal and bladder repair was successfully performed by single-incision laparoscopic surgery.
Vaginal delivery in COVID-19 pregnancies: experience from a referral center in a high...
Marta Lopez
Anna Goncé

Marta Lopez

and 9 more

May 13, 2020
Objective: We aimed to describe mode of delivery and perinatal results among COVID-19 confirmed infected women. Design: Prospective cohort of consecutive pregnant women with confirmed SARS-CoV-2 infection, and comparison of perinatal outcome with expected values on an historical cohort. Setting: A tertiary referral center in Barcelona, Spain. Population: Pregnant women with SARS-CoV-2 confirmed infection. Methods: SARS-CoV-2 infected women managed under a standard protocol who delivered during the period March 13th - April 25th, were evaluated. Data on baseline maternal characteristics, COVID-19 disease parameters, clinical management, mode of delivery, and perinatal outcome were collected. Relevant perinatal data were compared with the expected values observed in an historical control of our center. Main Outcome and Measure: Rate of vaginal delivery among COVID-19 pregnancies. Secondary outcomes were maternal or neonatal complications, and vertical transmission of SARS-CoV-2. Results: A total of 21 women with COVID-19 delivered at our center during the study period: 42.9% had moderate or severe respiratory infection. 14 out of 21 (66.7%) delivered vaginally. Three out of 7 caesarean sections were maternal indicated because of maternal worsening secondary to COVID infection. Preterm delivery occurred in 4 cases (19%), half of them related to COVID-19. There were no differences between the observed and the expected perinatal outcomes. Conclusions: In the absence of severe maternal complications, vaginal delivery among pregnant women with COVID-19 infection is a safe option, both for the mother and the baby, with similar perinatal outcomes than expected in a non-infected cohort and with no evidence of vertical transmission.
Detecting End-Point (EP) Man-In-The-Middle (MITM) Attack based on ARP Analysis: A Mac...
Jerry Kponyo
Justice Agyemang

Jerry Kponyo

and 2 more

May 13, 2020
End-Point (EP) Man-In-The-Middle (MITM) attack is a well-known threat in computer security. It targets the data flow between endpoints, and the confidentiality and integrity of the data itself. Several techniques have been developed to address this kind of attack. With the current emergence of machine learning (ML) models, we explore the possibility of applying ML in EP MITM detection. Our detection technique is based on address resolution protocol (ARP) analysis. The technique combines signal processing and machine learning in detecting EP MITM attack. We evaluated the accuracy of the proposed technique using linear-based ML classification models. The technique proved itself to be efficient by producing a detection accuracy of 99.72%.
Do we experience a prisoner's dilemma when choosing to wear a face mask?
Emmanuel ARIS

Emmanuel ARIS

May 13, 2020
To the Editor,Is it worth wearing a face mask? That is the question many people ask during the COVID-19 pandemic. To better understand answers of individuals to this question and their subsequent risk, we first recall the prisoner’s dilemma, a classic example of Game Theory, and then apply the same ideas to the decision of wearing a face mask.In the prisoner’s dilemma, two individuals, A and B, are arrested and put in a solitary confinement being both suspected of a robbery.1 Each of the prisoners has a choice between either testifying that the other committed the crime, or remaining silent. The prosecutor comes with the following offer to each prisoner separately: if you testify and the other remains silent, you will be free and the other will be imprisoned for three years, and vice versa. However, if you both testify, you will both get two years of imprisonment. Finally, if you both remain silent, you get one year each. At the personal level, testifying that the other did it is more interesting than remaining silent: if the other prisoner remains silent, testifying will get you free; if he testifies, testifying will result in two years in prison instead of three. Therefore, the two prisoners will tend to testify against each other and will get two years of imprisonment each. Meanwhile, if they had both cooperated and remained silent, they would both have ended up in a better situation as they would have been sentenced to one year of imprisonment instead of two.Consider now a group of N +1 individuals among whom contact patterns and disease transmission are the same in a situation where there is sustained human-to-human infection. Here, we are looking at the consequences of getting infected (P) if an individual i decides to wear a mask or not, and the effort (E) needed to get and wear the mask. Let C0 be the risk of i getting infected when all other N individuals wear a mask, and δ1, δ2, …, δN , the additional risk of getting infected when 1, 2, …, N subjects don’t wear a mask. Denote the percentage of protection obtained when wearing a mask by ε. The probability of i being infected and the effort needed when deciding to wear a mask or not, can be formulated as shown in Table 1.When, for example, r individuals do not wear a mask, if idecides to wear a mask, the effort f needed for this decision results in a decreased risk of infection is (C0+δ r)ε . Weighing this gain against the effort helps in choosing whether to wear a mask or not.At the individual level, i may well be tempted not to wear a mask: for non-surgical masks the gain (C0+δ r)ε can be low, as the level of protection can be small against submicron particles.2 In addition, if improperly manipulated, masks may even increase the risk of contamination.3 Finally, COVID-19 infection was reported to also happen via the eyes which are not covered by the mask.4 All this while a substantial effortf may be needed to be able to manage the discomfort and proper handling of the mask.However, if all the other individuals, reasoning like i , also decide not to wear masks the resulting risk of getting infected becomes C0 + δN . This would mean an increase of C0 ε + δN in infection risk compared to the situation where everyone wore a mask. The addition of δN to the reduction in infection risk can justify wearing a mask as δN is likely to be nonnegligible: if everybody, including the infected ones who are asymptomatic, but infectious, were wearing a mask, this could significantly reduce the virus transmission.5,6,7 In fact, the indirect protective effect of everybody else wearing a mask on decreasing the infection risk δN may be much higher than the direct protective effect (C0+δ r)ε of wearing a mask.Other factors may influence the decision of whether to wear or not a mask, but it is unlikely that the protective aspects and the burden linked to their use would not play significant roles in the decision of wearing them. Given a potentially weak protective effect, a significant effort needed to wear them, and a marked disease containment indirect effect, we may well end up in a prisoner’s dilemma situation. The question is then how to bring the individuals to cooperate and reach the optimal situation of wearing masks. Several options can be considered, spanning from simple encouragement to enforcement. Educating the public by explaining the benefit of everybody wearing even imperfectly sealed masks could provide a potentially cheap and effective measure.8Another option could be to lower the effort f by making good quality and easy to use masks widely available. These initiatives along with other incentives to foster a cooperative behaviour amongst individuals could be key to achieve widespread use of masks to fight against the COVID-19 pandemic, especially when easing lockdown restrictions.DisclaimerEmmanuel Aris is currently employed by GSK, but wrote this article in his personal capacity. The views expressed are his own and do not necessarily represent the views of GSK.References1. Nash J. Non Cooperative Games. Annals of Mathematics  1951;54: 286–295. DOI: 10.2307/1969529.2. Rengasamy S, Eimer B, Shaffer RE. Simple Respiratory Protection—Evaluation of the Filtration Performance of Cloth Masks and Common Fabric Materials Against 20–1000 nm Size Particles. Ann. Occup. Hyg. 2010; 54:789–798. DOI: 10.1093/annhyg/meq044. Epub 2010 Jun 28.3. World Health Organization. Advice on the use of masks in the community setting in Influenza A (H1N1) outbreaks. Interim guidance (3 May 2009). http://www.who.int/csr/resources/publications/Adviceusemaskscommunityrevised.pdf Date: 2020. Accessed April 20th 2020.4. Li JPO, Lam DSC, Chen Y, et al . Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear. Br J Ophthalmol 2020;104: 297-298. DOI:10.1136/bjophthalmol-2020-315994.5. Yu X, Yang R. COVID-19 transmission through asymptomatic carriers is a challenge to containment. Influenza Other Respi Viruses . 2020;00:1–2.6. Feng S, Shen C, Xia, N, et al . Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med 2020 https://doi.org/10.1016/ S2213-2600(20)30134-X.7. Johnson DF, Druce JD, Birch C, Grayson ML. A Quantitative Assessment of the Efficacy of Surgical and N95 Masks to Filter Influenza Virus in Patients with Acute Influenza Infection. Clinical Infectious Diseases 2009; 49: 275–277 DOI: 10.1086/600041.8. Greenhalgh T, Schmid, MB, Czypionka T, et al. Face masks for the public during the covid-19 crisis. BMJ , 2020;369:m1435 DOI: https://doi.org/10.1136/bmj.m1435.
Adding nebulized to systemic corticosteroids for acute asthma in children: a meta-ana...
Jose A. Castro-Rodriguez
Mauricio Pincheira

Jose Castro-Rodriguez

and 4 more

May 13, 2020
International guidelines have recommended the use of inhaled beta-2 agonists and systemic corticosteroids (SC) as the first-line treatment for acute asthma. Objective: To evaluate the evidence for the efficacy of inhaled corticosteroids (ICS) in addition to SC compared to SC alone in children with acute asthma in the ED or during hospitalization. Data sources: Five electronic databases were searched. Study Selection: All RCTs that compared ICS (via nebulizer or metered dose inhaler) plus SC (oral or parenteral) with placebo (or standard care) plus SC were included without language restriction. Data extraction: Two reviewers independently reviewed all studies. The primary outcomes were hospital admission or hospital length of stay [LOS], and secondary outcomes were readmissions during follow-up, ED-LOS, lung function, asthma clinical score, oxygen saturation, and heart and respiratory rates. Results: Nine studies (n=1473) met the inclusion criteria. In all the studies, the ICS was budesonide. Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreased hospital LOS by more than one day (MD= -29.08 hours [-39.9 to -18.3]; I2=0%, p=<0.00001). Moreover, adding budesonide (especially with ≥2mg doses) significantly improved the acute asthma severity score among patients at ED. Conclusions: Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreases the LOS and improves the acute asthma score in children at ED setting.
The Cost‑Utility of Intravenous Magnesium Sulfate for Treating Acute Asthma in Childr...
jefferson buendia
Ranniery Acuña-Cordero

jefferson buendia

and 2 more

May 13, 2020
Introduction Despite the evidence supporting the use of intravenous Magnesium Sulfate (MS) in acute asthma; this drug continues being considered as the second line in pediatric acute asthma exacerbations. This study aimed to evaluate the cost-effectiveness of the MS in acute asthma. Methods A decision tree model was used to estimate the Cost-utility study that compared MS versus standard treatment (control group) in an infant with acute asthma in the emergency setting. Cost data were obtained from a retrospective study on asthma from tertiary centers in Rionegro, Colombia, while utilities were collected from the literature. The analysis was carried out from a societal perspective. Results The model showed that MS for treating pediatric patient with acute asthma, was associated with lower total cost than standard therapy (US $1149 vs US $1598 average cost per patient), and higher QALYs ( 0.60 vs 0.52 average per patient); showing dominance. the probabilty that MS provides a more cost-effective use of resources compared with standard therapy exceeds 99% for all willingness to pay thresholds Conclusion MS in emergency settings was cost-effective for the hospital treatment of an infant with asthma moderate or severe. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.
Covid-19 -- is it less severe in asthmatic and allergic children?
Chandra Sekhar Devulapalli

Chandra Sekhar Devulapalli

May 13, 2020
It has been widely reported that vast majority of children have experienced only mild symptoms in the ongoing COVID-19 pandemic outbreak. It also appears that children have a minimal risk of developing COVID-19 and also minimal risk of a fatal outcome. Reasons for this is largely unknown in the present circumstances. Patients with severe and uncontrolled asthma have also been classified to be at increased risk of developing more severe COVID-19. It has been earlier speculated that children were less sensitive to COVID-19 because the maturity and binding ability of angiotensin-converting enzyme-2 (ACE2) in children may be lower than in adults. A recent study indicate that children with asthma and allergies have reduced ACE2 gene expression due to down-regulation of the ACE2 receptor. It is conceivable that virus-induced immune response and subsequent tissue damage may be less pronounced in children. So far, there is no evidence to suggest that children with chronic diseases like asthma and allergy will have a more severe reaction to COVID-19.
Approach to patient with cough by American and Chinese respiratory specialist
Xiuxiu Liu
Deniz Kesebir

Xiuxiu Liu

and 2 more

May 13, 2020
Cough is a common pediatric complaint. Acute cough is often considered to be self-limiting and not requiring particular management. However, pediatric patients and their parents often seek remedy for acute cough. Traditional Chinese Medicine (TCM) Specialists have been treating pediatric cough for millenniums. Here we present a case of pediatric cough and approach to it by Western and Chinese Respiratory Specialist. We conclude that TCM may provide important and useful insight on treatment of pediatric respiratory diseases.
Covid and A Call for Reinventing Medical Education
Omar Lattouf

Omar Lattouf

May 13, 2020
Covid has blatantly uncovered the disconnect between the healthcare professionals who have the responsibility for the health of the nation but little of the authority, and politicians and business people who have the authority and political power over healthcare, but none of the responsibility for the health of the nation. The time has come to review this dichotomy and to reinvent medical education in order to empower and train healthcare professionals, particularly mid-career ones, to become adept in the business of medicine; including budgeting, management, leadership, hiring and firing, brand building and other important aspects of running complex healthcare entities. It is no longer acceptable for physicians to accept backseat for non-physician managers and concede their rules and regulations without question. The time is now for health professionals to train themselves and take charge of the profession.
Finite Element analysis on the stress behavior of Steel Spring and Metal Matrix compo...
Harmeet Singh

Harmeet Singh

May 13, 2020
Aluminum-based metal matrix composite material found to be the best alternative to make auto components with its unique mechanical properties and lightweight. This present work, an attempt has made to use finite element based software to find out stress analysis of steel spring and composite leaf spring. EN 45 steel spring used in automobile vehicles has selected as principle application. For analysis purposes, metal matrix composite based leaf spring prepared and compared with steel leaf spring. The main objective of this research work to find the possibilities to replace the steel spring by metal matrix composite based leaf spring. Finite element based software ANSYS 18.0 was used for analysis purposes. The Result showed that metal matrix composite leaf spring has 38% less stress as compared to the steel spring. Compared to steel spring, the composite leaf spring has 50% less weight.
“Daily medical liaison is associated with reduced length of stay in a regional vascul...
Emma Mitchell
Roisin Coary

Emma Mitchell

and 8 more

May 13, 2020
Objective: To determine the impact of the introduction and establishment of a daily medical liaison service provided to patients aged 65 years and older attending a regional vascular surgery centre. Methods and Analysis: Descriptive before-and-after study concerning 375 patients (pre-intervention n=171, post-intervention n=204). Retrospective case-note analysis during two three-month periods (January-March, 2017 and 2018). Intervention comprised daily senior-led medical liaison review. Primary outcome measure was length of stay (LOS). Results were analysed using SPSS Statistics 23. Descriptive analyses were performed in addition to correlation and regression analyses to identify key predictors of postoperative outcome. Results: There was a trend reduction in LOS from 10.75 to 7.95 days (p=0.635, 95% CI 0 – 1 day) with a significant reduction in mean LOS for patients admitted for longer than seven days (7.84 days, p=0.025, 95% CI for mean difference, 1.5 to 14 days). This group also benefited reduced 30-day readmission rates (12/60 to 8/72, p=0.156, 95% CI -3% to 21%). Trend reduction in the number of postoperative complications was seen (1.09 to 0.86 per person, p=0.181, 95% CI -0.11 to 0.56), which reached statistical significance in emergency vascular admissions (1.81 to 0.97 per person, p=0.01, mean difference = 0.84, 95% CI 0.21 – 1.46). Conclusion: This study has demonstrated reduced LOS and complications associated with daily medical liaison in selected older patients admitted under vascular surgery. The greatest benefit appears to be in patients admitted for more than seven days or in emergency admissions. These data are amongst the first to reproduce randomised control trial findings in a non-trial setting. They indicate which patient groups may benefit most from collaborative models of care where resources are finite.
Severity of hypertension as a predictor of initiation of dialysis among study partici...
Taeko Osawa
Kazuya Fujihara

Taeko Osawa

and 11 more

May 13, 2020
Aims: To determine associations between severity of hypertension and risk of starting dialysis in the presence or absence of diabetes mellitus (DM). Methods: A nationwide database with claims data on 258,874 people with and without DM aged 19-72 y in Japan was used to elucidate the impact of severity of hypertension on starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modeling, we investigated severity of hypertension as a predictor of the initiation of dialysis with and without DM. Results: Hypertension was significantly associated with the initiation of dialysis regardless of DM. The incidence of starting dialysis in those with SBP ≤119 mmHg and DM (DM+) was almost the same as in those with SBP ≥150 mmHg and absence of DM (DM-). In comparison with SBP ≤119 mmHg, SBP ≥150 mmHg significantly increased the risk of the initiation of dialysis about 2.5 times regardless of DM+ or DM-. Compared with DM- and SBP ≤119mmHg, the HR for DM+ and SBP ≥150 mmHg was 6.88 (95% CI 3.66-12.9). Conclusions: Although the risks of hypertension differed only slightly regardless of the presence or absence of DM, risks for the initiation of dialysis with DM+ and SBP ≤119 mmHg were equivalent to DM- and SBP ≥150 mmHg, indicating more strict blood pressure interventions in DM+ are needed to avoid dialysis. Future studies are needed to clarify the cut-off SBP level to avoid initiation of dialysis considering the risks of strict control of blood pressure.
Dose Prediction for Repurposing Nitazoxanide in SARS-CoV-2 Treatment or Chemoprophyla...
Rajith Rajoli
Henry Pertinez

Rajith Rajoli

and 22 more

May 13, 2020
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic and urgent treatment and prevention strategies are needed. Nitazoxanide, an anthelmintic drug has been shown to exhibit in vitro activity against SARS-CoV-2. The present study used physiologically-based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported nitazoxanide SARS-CoV-2 EC90. Methods: A whole-body PBPK model was validated against available pharmacokinetic data for healthy individuals receiving single and multiple doses between 500–4000 mg with and without food. The validated model was used to predict doses expected to maintain tizoxanide plasma and lung concentrations above the nitazoxanide EC90 in >90% of the simulated population. PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. Results: The PBPK model was successfully validated against the reported human pharmacokinetics. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated. Conclusion: The PBPK model predicted tizoxanide concentrations within doses of nitazoxanide already given to humans previously. The reported dosing strategies provide a rational basis for design of clinical trials with nitazoxanide for the treatment or prevention of SARS-CoV-2 infection.
Parosmia is associated with relevant olfactory recovery after olfactory training
David Liu
Maha Sabha

David Liu

and 6 more

May 13, 2020
Objectives This study aims to determine the association between parosmia and clinically relevant recovery in olfactory function in patients with smell loss receiving olfactory training. Design and setting This was a retrospective cohort study of patients that received olfactory training. Adult patients with the major complaint of quantitative smell loss were recruited and treated at several ENT clinics in German between 2008 and 2018. Participants A total of 243 participants were included. Main outcome measures Changes in olfactory function after olfactory training. Age, gender, baseline olfactory function, etiology and duration of smell loss, duration of training, and presence of parosmia and phantosmia were assessed for their impact on clinically relevant changes in overall and subdimension olfactory function using binary logistic regression analysis. Results Relevant improvements in discrimination function were more likely in those that had lower baseline olfactory function, postinfectious reasons compared to posttraumatic or idiopathic causes and those that had parosmia at initial visit. Relevant improvements in odour identification were more likely in those that had a lower baseline olfactory function, female gender, and in those who had parosmia at the first visit. Clinically significant improvements in odour threshold were more likely in postinfectious causes compared to posttraumatic reasons and those who were older in age. Conclusions This study demonstrated that the presence of parosmia is associated with clinically relevant recovery in olfactory function in patients with smell loss receiving olfactory training.
Anaphylaxis to drugs: overcoming mast cell unresponsiveness by fake antigens
Werner Pichler

Werner Pichler

May 13, 2020
Our understanding of IgE-mediated drug allergy relies on the hapten concept, which is well established in inducing reactions of the immune system to small molecules like drugs. The role of hapten-carrier adducts in re-challenge reactions leading to mast cell degranulation and anaphylaxis is unclear. Based on clinical observations, the speed of adduct formation, skin and in-vitro tests to inert drug molecules, a different explanation of IgE-mediated reactions to drugs is proposed: These are a) A natural role of reduced mast cell (MC) reactivity in developing IgE-mediated reactions to drugs. This MC-unresponsiveness is antigen-specific and covers the serum drug concentrations, but allows reactivity to locally higher concentrations. b) Some non-covalent drug-protein complexes rely on rather affine bindings and have a similar appearance as covalent hapten-carrier adducts. Such drug-protein complexes represent so-called “fake antigens”, as they are unable to induce immunity, but may react with and crosslink preformed drug-specific IgE. As they are formed very rapidly and in high concentrations, they may cause fulminant MC degranulation and anaphylaxis. c) The generation of covalent hapten-protein adducts requires hours, either because the formation of covalent bonds requires time or because first a metabolic step for forming a reactive metabolite is required. This slow process of stable adduct formation has the advantage that it may give time to desensitize mast cells, even in already sensitized individuals. The consequences of this new interpretation of IgE mediated reactions to drugs are potentially wide-reaching for IgE-mediated drug allergy but also allergy in general.
SARS-CoV-2, skin lesions and the role of the allergist
Raquel Cabrera-Hernández
Emilio Solano

Raquel Cabrera-Hernández

and 11 more

May 13, 2020
To the Editor:COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 of the genus Betacoronavirus (SARS-CoV-2). It was first described in Wuhan (China) on December 2019 and has spread to become a pandemic. Its clinical presentation is mainly characterized by cough, fever and dyspnea, although many other symptoms have been described within its presentation pattern. In some cases, it causes an acute respiratory distress that has lead to the death of thousands of people around the world. Furthermore, different type of skin lesions have been described during the infection period of illness due to SARS-CoV-2.1 The first report of cutaneous manifestations described different forms of skin lesions such as erythematous rash, urticaria and chicken-pox-like vesicles.2 In this exceptional situation of global health emergency, physicians are undertaking research work in order to achieve notions on the etiopathogenesis of these skin lesions. Acro-ischaemic lesions have also been notified and attributed to disseminated intravascular coagulation and to the expression of secondary microthrombosis due to endotelial damage.3-5However, to date, there is no clear understanding on whether the skin lesions are secondary to the viral infection nor why there are different presentations of skin lesions for the same viral infection.We present 4 patients with COVID-19, confirmed by positive polymerase chain reaction, who were referred to our service due to the appearance of skin lesions. Two of them developed skin lesions during hospitalization whilst presenting respiratory symptoms and the other two developed skin lesions many days after hospital discharge. Demographic data, description and histology of skin lesions, blood parameters, clinical symptoms and drugs administered are shown in table I. The algorithm of the spanish pharmacovigilance system (ASPS), which evaluates the possible implication of a drug reaction as a cause of the skin lesions6 was also applied. The ASPS analizes: i) the interval between drug administration and the aparition of skin lesions, ii) the degree of knowledge of the relationship between the drug and the effect described in literature, iii) the evaluation of drug withdrawal, iv) the rechallenge effect, and v) alternative causes. Each item receives and individual subscore, and a total sum ≥ 6 indicates a probable causality.6As mentioned above, skin lesions appear to be a sign within patients suffering from COVID-19. To date, no hypothesis has been proposed to explain if the lesions (including the different types) are attributable to the virus, to drug adverse reactions or to any other clinical condition. In our series, small enough to draw conclusions, we have found no differences between the multiple types of skin lesions and analytical or clinical features. Even in lesions with apparent vascular involvement, which have been associated with alterations in coagulation,3-5 the values detected do not differ from those with other types of skin lesions. Regarding drug involvement, since all the patients were exposed to multiple drugs at the same time, the ASPS was not able to differentiate the possibility of drug implication nor the immune mechanisms involved. Thus, further assays with selective (in vitro or in vivo ) tests for each drug seem necessary in order to completely rule out drug involvement. In addition, since many patients worldwide are being infected with SARS-Cov-2, and many of them present similar medical history and receive the same treatments, it seems necessary to investigate the existence of an individual predisposition that facilitates the developement of skin lesions. In this new scenario that we are facing in these last months, providing light on these still unresolved questions, can contribute to prevent or to manage the symptoms in an early way.
The Impact of Implicit Bias in the Pandemic Age: Protecting our Pediatric Patients
Valeria Martinez-Kaigi

Valeria Martinez-Kaigi

May 13, 2020
In the midst of a global public health crisis, medical providers find themselves on the frontline of unprecedented circumstances caring for patients as they fight the coronavirus disease 2019 (COVID-19) pandemic. Pediatricians are faced with the reality that COVID-19 positions marginalized groups of children and youths at an increased vulnerability to health care inequities. These at-risk groups include children and youth who are ethnic and racial minorities, immigrants, LGBTQ, homeless, in foster care, as well as those who have medically complex health conditions and/or mental health and substance use disorders (1, 2, 3). Now more than ever, health disparities have the potential to result in fatal health outcomes and healthcare professionals have the power to advocate for and protect their young patients. Given the urgent and pressing impacts of the current pandemic, Tsai and Kesselheim offer a timely and critical dialogue in this issue of Pediatric Blood & Cancer, focused on the effects of provider implicit bias that contribute to health disparities.Tsai and Kesselheim underscore the well documented literature on implicit bias in pediatric medical oncology and note the limited research in pediatric hematology-oncology, despite the complexities that exists in prognosis and treatment plans for this clinical population. Additionally, the case examples are thoughtful, transparent self-reflections from the authors personal clinical experiences with implicit bias in the field of pediatric hematology-oncology. The authors then outline a plan of action towards mitigating implicit bias in healthcare. They first emphasize the importance of acknowledging implicit bias, which is ubiquitous in human nature and exists under many circumstances. Subsequently, upon acknowledgment of existing implicit bias, providers should cultivate self-awareness via medical education in order to have the autonomy and ability to identify and detect implicit bias that negatively affect patient care. Moreover, the authors deduce that diversifying the medical team, both demographically and interprofessionally, can optimize detection of implicit bias. The authors go on to conclude that more research is needed in the specialty field of hematology-oncology to identify how implicit bias specifically affects provider’s ability to communicate complex diagnoses, prognoses, and treatment options.Derived from social psychology research, implicit bias refers to unconscious, unintentional, and automatic positively or negatively skewed classifications people make based on their own experiences and demographic background which then influences behavior and perceptions. The Institute of Medicine published a pivotal report illuminating how implicit bias can negatively influence patient care and may lead to health disparities (4). Examples of implicit bias affecting health outcomes include biases toward race, weight, sexual orientation, socioeconomic status, age, marital status and history of drug use (5, 6). There are two paths that may explain how implicit bias amongst medical providers may contribute to health disparities (5, See Figure 1). Path A suggests provider judgements and decisions regarding patient care can result in health disparities. Path B proposes that implicit bias amongst providers can lead to ineffective communication which affects the providers ability to cultivate a trusting relationship and environment. Patient’s distrust with their providers affects their willingness and ability to adhere to treatment recommendations which subsequently leads to health disparities. Moreover, this model also explains the conduit for interaction effects between path A and B. That is, compromised judgment leading to poor medical decisions may strengthen the probability of poor communication and distrust in the provider-patient relationship or the inverse. Also imperative to the discourse of health disparities and bias, not discussed by Tsai and Kesselheim, is the notion of “privilege” that, unlike minorities, many non-minorities may experience in their rise to becoming a medical professional as well as their medical decision making (7). Such privilege can inadvertently bias providers to behave in ways that illuminate implicit bias. Therefore, the ability to acknowledge privilege is essential to increasing one’s proclivity to recognize their implicit biases. The authors provide vignettes that pointedly describe the importance of self-awareness. Practicing self-awareness promotes the ability to detect implicit biases that may affect patient care and result in unintentional health disparities. Moreover, central to the author’s argument, it is fundamentally important to identify and implement practical steps to address provider implicit bias.The use of research to inform best clinical practice by implementing skills training is key in addressing health disparities related to provider implicit bias. A potential barrier to successful training and education on provider implicit bias is limited support from institutional leadership (8). Committed leadership on curricula related to implicit bias at an institutional level is likely to reflect long-term systemic change (9, 10). Furthermore, providing a nonjudgmental and safe environment for providers to address difficult content is also key in fostering self-awareness that is more likely to result in long-term change (10). Considering the role of power dynamics in practice and training is also fundamental for cultivating a safe environment for self-disclosure and self-awareness and bringing about systemic long-standing modifications. Tsai and Kesselheim highlight the importance of building demographically diverse and interdisciplinary medical teams. Purposeful team development can also reveal and mitigate any systemic workforce and recruitment biases (11). Having various perspectives while discussing a treatment plan can combat implicit bias. For example, if a complex case is presented at morning rounds with a team that is homogeneous in background and trainings there is potential for groupthink that is anchored in one or two individuals’ implicit biases. Specific to complex cases in pediatric hematology-oncology this can be critical especially during a pandemic that is particularly impacting vulnerable populations, who are often less likely to be represented among medical decision makers. A diverse team can provide insight for culturally competent care as well as provide important perspectives that could optimize diagnostic and treatment outcomes.As a clinician, it is not an easy task to be open to becoming vulnerable to exploring self-awareness as it relates to implicit bias. It is also our ethical duty to do no harm. Acknowledging implicit bias as a catalyst to health disparities while implementing effective skills training to address implicit bias is crucial to protecting our most vulnerable pediatric patients.ReferencesSilliman Cohen RI, Adlin Bosk E. Vulnerable youth and the COVID-19 pandemic. Pediatrics . 2020; doi: 10.1542/peds.2020-1306Cholera R, Falusi OO, Linton JM. Sheltering in place in a xenophobic climate: 12 COVID-19 and children in immigrant families. Pediatrics. 2020; doi: 10.1542/peds.2020-1094Wong CA, Ming D, Maslow G, Gifford EJ. Mitigating the impacts of the COVID-19 pandemic response on at-risk children. Pediatrics . 2020; doi: 10.1542/peds.2020-0973Smedley BD, Stith SY, Nelson AR, Smedley BD, Stith SY, Nelson AR, editors. Unequal treatment: confronting racial and ethnic disparities in health care. Institute of Medicine. National Academies Press; Washington, D.C: 2002. doi.org/10.17226/12875Zestcott C, Blair I, Stone J. Examining the presence, consequences, and reduction of implicit bias in health care: A narrative review. Group Processes & Intergroup Relations . 2016;19(4):528-542. doi:10.1177/1368430216642029DelFattore J. Death by Stereotype? Cancer Treatment in Unmarried Patients. New England Journal of Medicine . 2019;381(10):982-985. doi:10.1056/nejmms1902657Hall J, Carlson K. Marginalization. Advances in Nursing Science . 2016;39(3):200-215. doi:10.1097/ans.0000000000000123Dehon E, Weiss N, Jones J, Faulconer W, Hinton E, Sterling S. A Systematic Review of the Impact of Physician Implicit Racial Bias on Clinical Decision Making. Academic Emergency Medicine. 2017;24(8):895-904. doi:10.1111/acem.13214Pereda B, Montoya M. Addressing Implicit Bias to Improve Cross-cultural Care. Clin Obstet Gynecol . 2018;61(1):2-9. doi:10.1097/grf.0000000000000341Sherman M, Ricco J, Nelson S, Nezhad S, Prasad S. Implicit Bias Training in Residency Program: Aiming for Enduring Effects. Fam Med. 2019;51(8):677-681. doi:10.22454/fammed.2019.947255Hall W, Chapman M, Lee K et al. Implicit Racial/Ethnic Bias Among Health Care Professionals and Its Influence on Health Care Outcomes: A Systematic Review. Am J Public Health. 2015;105(12):2588-2588. doi:10.2105/ajph.2015.302903a
Reassessing Sarcopenia In Hypertension: STAR and ACE Inhibitors Excel
Ayşe Merve Ata
Murat Kara

Ayşe Merve Ata

and 9 more

May 13, 2020
Background: Hypertension and sarcopenia are commonly seen in older adults. The renin-angiotensin system and the therapeutic use of angiotensin converting enzyme (ACE) inhibitors have been on the agenda of sarcopenia in different perspectives. Our aim was to explore the frequency of sarcopenia in patients with hypertension and to investigate the association between the use of ACE inhibitors and sarcopenia. Methods: A total of 233 community dwelling adults were recruited. Anterior thigh muscle thickness was measured by ultrasound. Handgrip strength, gait speed and chair stand test were evaluated. Presarcopenia was diagnosed in the presence of low sonographic thigh adjustment ratio (STAR) values and sarcopenia was diagnosed if low STAR values were coupled with low functional tests. Results: 109 subjects (46.8%) had no comorbid disease; 93 (75.0%) had one, 21 (16.9%) had two, eight (6.5%) had three and two (1.6%) had four comorbid diseases. Both presarcopenia (48.3% vs. 21.1%) and sarcopenia (33.3% vs. 7.0%) were more commonly seen in hypertensive when compared to normotensive older adults. Subgroup analysis of older adults with hypertension revealed that sarcopenia was less prevalent (p=0.020) in patients using ACE inhibitors (9.1%) than those using angiotensin receptor blockers (ARBs) (40.5%) and other antihypertensive drugs (42.9%). After binary logistic regression analyses; only the presence of hypertension seemed to independently predict the development of sarcopenia in older adults [OR=7.9 (95% CI: 2.6-24.5, p<0.001)]. Conclusions: Sarcopenia is highly prevalent in hypertensive older adults. Among many antihypertensive medications, ACE inhibitors seem to have favorable effects on both disorders.
Ecosystem carbon storage following different approaches to grassland restoration in s...
ji yuan
Zhiyun Ouyang

ji yuan

and 3 more

May 13, 2020
Global climate change and extensive socio-economic development together decrease ground cover in the semi-arid sandy grasslands of Horqin district in northern China and thereby increase the direct exposure of surface soil to erosion by strong winds—a process that ultimately converts the grassland into a sandy desert. Three ways to restore such degraded lands through afforestation were evaluated in terms of total carbon stored in the restored ecosystems compared to that in the control. Total carbon comprised that stored in the biomass of trees, herbs, and standing litter and in soil (up to a depth of 100 cm). The three restoration treatments were (1) enclosing the grassland within a shelter belt of Populus × beijingensis, (2) afforesting small but well-distributed patches within the grassland using Pinus sylvestris var. mongolica, and (3) similar afforestation using Ulmus pumila. Total ecosystem carbon storage increased significantly in all the three treatments over more than 20 years; at the end of that period, total ecosystem carbon was maximum (104.29 t/ha) in the grassland enclosed by the forest belt, followed, in that order, by afforestation with P. sylvestris (102.96 t/ha), that with U. pumila (92.24 t/ha), and the control (24.48 t/ha). The structure of the plant community created by these treatments is different from that found in natural stands of forest and in grasslands without trees or shrubs, and all the three treatments are suitable for restoring the moderately desertified sandy grasslands in south-eastern Horqin, northern China, depending on the availability of water and soil nutrients.
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