ARTICLE | doi:10.20944/preprints202010.0200.v1
Subject: Medicine & Pharmacology, Other Keywords: digital reference object; blood-brain barrier permeability; DCE-MRI; Spatio-temporal imaging artefacts; endothelial dysfunction; cerebral small vessel disease
Online: 9 October 2020 (12:44:33 CEST)
Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.
Thu, 24 September 2020
REVIEW | doi:10.20944/preprints202009.0579.v1
Subject: Medicine & Pharmacology, Other Keywords: stray dogs; Pasteur Institute; vaccination; colonial; British India; Civil Veterinary Department
Online: 24 September 2020 (11:13:30 CEST)
India bears the highest burden of global dog-mediated human rabies deaths. Despite this, rabies is not notifiable in India, and continues to be underprioritized in public health discussions. This review examines the historical treatment of rabies in British India, a disease which has received relatively less attention in the literature on Indian medical history. Human and animal rabies was widespread in British India and treatment of bite victims imposed a major financial burden on the colonial Government of India. It subsequently became a driver of Pasteurism in India and globally and a key component of British colonial scientific enterprise. Efforts to combat rabies led to the establishment of a wide network of research institutes in India and important breakthroughs in development of rabies vaccines. As a result of these efforts, rabies no longer posed a significant threat to the British and it declined in administrative and public health priorities in India towards the end of colonial rule; a decline that has yet to be reversed in modern-day India. The review also highlights features of the administrative, scientific and societal approaches to dealing with this disease in British India which persist to this day.
ARTICLE | doi:10.20944/preprints202009.0573.v1
Subject: Medicine & Pharmacology, Other Keywords: healthcare-associated infections; HCAIs; hospital acquired infections; nosocomial infections; statistical analysis
Online: 24 September 2020 (08:19:38 CEST)
Statistical data on officially registered cases of health care-associated infections (HCAIs) in Ukraine in the period 2009-2019 have been analysed. On average, 5089±756 cases of HCAIs were registered annually. Odessa region of Ukraine is the leading country in the number of reported cases. The majority of HCAIs cases involve surgical and therapeutic invasive interventions and perinatal HCAIs. On average, 78.0±5.8 % of HCAIs cases involved adults. The estimated minimum number of HCAIs in Ukraine was expected to be about 1 million per year. Official statistics on registered cases of HCAIs in Ukraine do not reflect reality, so the system of registration and investigation of HCAIs in Ukraine needs to be reformed.
Wed, 23 September 2020
ARTICLE | doi:10.20944/preprints202008.0204.v2
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-Cov-2; epidemic surveillance; emerging infectious disease; epidemic threshold
Online: 23 September 2020 (11:10:15 CEST)
Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2,000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26th 2020 and the sanitary alert on March 3rd. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.
CASE REPORT | doi:10.20944/preprints202009.0543.v1
Subject: Medicine & Pharmacology, Other Keywords: genetics； comparative genomics； phylogenetic analysis； osteopetrosis； CLCN7 gene
Online: 23 September 2020 (07:56:30 CEST)
Osteopetrosis is a group of rare inheritable disorders of the skeleton characterized by increased bone density. The disease is remarkably heterogeneous in clinical presentation and often misdiagnosed. Therefore, genetic testing and molecular pathogenicity analysis are essential for precise diagnosis and new targets for preventive pharmacotherapy. Mutations in the CLCN7 gene give rise to the complete spectrum of osteopetrosis phenotypes and are responsible for about 75% of cases of autosomal dominant osteopetrosis. In this study, we report the identification of a novel variant in the CLCN7 gene in a patient diagnosed with osteopetrosis and provide evidence for its significance (likely deleterious) based on extensive comparative genomics, protein sequence and structure analysis. A set of automated bioinformatics tools used to predict consequences of this variant identified it as deleterious or pathogenic. Structure analysis revealed that the variant is located at the same “hot spot” as the most common CLCN7 mutations causing osteopetrosis. Deep phylogenetic reconstruction showed that not only Leu614Arg, but any non-aliphatic substitutions in this position are evolutionarily intolerant, further supporting the deleterious nature of the variant. The present study provides further evidence that reconstructing a precise evolutionary history of a gene helps predicting phenotypical consequences of variants of uncertain significance.
REVIEW | doi:10.20944/preprints202009.0535.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Pandemic; Global health; Health inequalities
Online: 23 September 2020 (04:13:51 CEST)
The COVID-19 crisis has brought unprecedented strain on healthcare systems around the world. It has perhaps taught us some key lessons that are worth considering and addressing to help build more sustainable health systems as well as improve our ability to combat future epidemics.
ARTICLE | doi:10.20944/preprints202009.0532.v1
Subject: Medicine & Pharmacology, Other Keywords: adipose derived regenerative cells; ADRCs; efficacy; point of care treatment; stem cells; stromal vascular fraction; tendon healing without scar formation; tendon regeneration
Online: 23 September 2020 (03:49:36 CEST)
Current clinical treatment options for symptomatic rotator cuff tear offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with autologous, adipose derived regenerative cells. Here we demonstrate, for the first time, a comprehensive histological and immunohistochemical analysis of the biopsy of a supraspinatus tendon of a 66-year-old subject with traumatic rotator cuff injury, taken ten weeks after local injection of fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs), prepared at the point of care. Our analysis demonstrated clear evidence towards regenerative healing of the injured supraspinatus tendon. Of note, no formation of adipocytes was observed. These findings indicate that injected autologous, unmodified stem cells can indeed form new tendon tissue and regenerate an injured human tendon.
Tue, 22 September 2020
ARTICLE | doi:10.20944/preprints202009.0517.v1
Subject: Medicine & Pharmacology, Other Keywords: chemonucleolysis; condoliase; chondroitin sulfate ABC endolyase; lumber disc herniation
Online: 22 September 2020 (10:02:01 CEST)
Background and Objectives: Chondroitin sulfate ABC endolyase (condoliase) was launched as a new drug for chemonucleolysis in 2018. There are few Few studies assessed regarding its clinical outcomes, and many important factors matters still remain unclear. The purpose of this This study aimed is to clarify clarify the preoperative conditionsfactors for in which condoliase could beis highly effective. Materials and Methods: Of the 47 patients who received condoliase, 34 patients were enrolled in this study. The mean age of the patients was 33 years. The average disease duration since the onset of the disease was 8.6 months. We evaluated the patients’patient’s low back and leg painpains using a numericalNumerical rating scale (NRS) score at two time points (before therapy and 3 months after therapyadministration). We divided the patients into two groups ([good group [(G]:): NRS score improvement ≥ 50%, poor group (P): NRS score improvement < 50%]. The parameters evaluatedSurvey items were age, disease disease duration, body mass index (BMI), and the presence or absence of positive or negative straight leg raising (SLR) test results. In additionMoreover, the loss of disc height loss and participation of preoperative radiological findings were also evaluated. Results: In terms of low back and leg pain, the G group were in 9/34 (26.5%) and 21/34 (61.8%) patients, respectively. Patients’. Patient’s age (low back pain G/P, 21.0/36.5 years)), was significantly loweryounger in the G group of low back pain (p = 0.001). High intensity change inof the protruded nucleus pulposus (NP) and the spinal canal occupancy by theof NP ≥ 40% were significantly highhighly observed in those withthe leg pain in the G groups (14/21,: p = 0.04; and 13/21,: p = 0.03, respectively). Conclusions: The efficacy of improvement inof leg pain was significantlyhighly correlated with high intensity change and size of the protruded NP. Condoliase was not significantly effective forto low back pain, but could might be expected have anthe effect onto younger patients.
ARTICLE | doi:10.20944/preprints202009.0510.v1
Subject: Medicine & Pharmacology, Other Keywords: Hydrogel; pH-responsive; colon; targeted delivery; methotrexate
Online: 22 September 2020 (08:17:48 CEST)
The purpose of current research work was to formulate and typify gelatin and poly(vinyl) alcohol (Gel/PVA) hydrogel which would be highly pH-responsive and can able to accomplish targeted delivery of methotrexate in order to treat the colo-rectal pathologies. The primed gel/pva hydrogel discs were subjected to various physicochemical techniques i.e. swelling, diffusion co-efficient, sol-gel analysis and porosity using three altered sorts of pH (1.2, 6.8 & 7.4) phosphate buffer solutions for assessment/evaluation, and their characterization was done through Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA). Shape alteration and controlled methotrexate of release of Gel/PVA hydrogel have been done using three type of pH (1.2, 6.8 & 7.4) phosphate buffer mediums. Methotrexate was loaded through in-situ drug loading method due to hydrophobicity. Different kinetic models (first order & zero order kinetic), Higuchi model and Krosmere peppas model/Power law were applied to manipulate the drug release data. Physicochemical evaluation tests and drug release profile results were found insignificant (p< 0.05) in various pH mediums and dependent upon polymers concentration pH of medium and cross-linker amount. Kinetic model disclosed that release of methotrexate from Gel/PVA hydrogel follow non-Fickian diffusion method. It became concluded from this research work that release of methotrexate Gel/PVA hydrogel in targeted colon area can be achieved for treating colo-rectal disorders.
Sat, 19 September 2020
ARTICLE | doi:10.20944/preprints202009.0446.v1
Subject: Medicine & Pharmacology, Other Keywords: Novel coronavirus diseases 2019; vaccination; target population; China
Online: 19 September 2020 (05:02:54 CEST)
All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.
Fri, 18 September 2020
REVIEW | doi:10.20944/preprints202009.0425.v1
Online: 18 September 2020 (09:58:49 CEST)
The Coronavirus disease 2019 (COVID-19) pandemic is clearly taking a firmer grip on South Africa and more podiatrists will face the potential transmission of SARS-CoV-2. Government response was swift with the implementation of a travel ban, strict national lockdown as well as social distancing and hygiene protocols in line with international health regulations. Co-morbidities such as tuberculosis and HIV/AIDS, endemic to South Africa, are considered a dangerous combination with COVID-19, making many South Africans vulnerable to contracting the COVID-19. Patients with diabetes as well as the aged are vulnerable, both in terms of potential combined complications and challenges in continuity in foot care. The demands of the pandemic may outstrip the ability of the health systems to cope. Should this time arrive, all healthcare practitioners, including podiatrists, would have to step in and take on a role beyond their scope of practice in order to ensure that the healthcare system does not get overwhelmed. It is important for podiatrists to keep abreast with the developments around the COVID-19, in order that they may institute appropriate clinical practice which will ensure maximum protection for themselves, staff and patients as well as providing quality foot health care.
ARTICLE | doi:10.20944/preprints202009.0423.v1
Subject: Medicine & Pharmacology, Other Keywords: community-dwelling older adults; physical frailty; prevalence; risk factors
Online: 18 September 2020 (08:57:56 CEST)
Frailty is defined as a state of increased vulnerability to stressors, and it predicts the disability and mortality in the older population. This study aimed to investigate standardized prevalence and multidimensional risk factors associated with frailty among the Korean community-dwelling older adults. We analyzed the baseline data of 2,907 adults aged 70–84 years (mean age 75.8±3.9 years, 57.8% women) in the Korean Frailty and Aging Cohort Study. The Fried frailty phenotype was used to define frailty. Analyzed data included sociodemographic, physical, physical function, biological, lifestyle, health condition, medical condition, psychological, and social domains. Data were standardized using the national standard population composition ratio based on the Korean Population and Housing Census. The standardized prevalence of frailty and pre-frailty was 7.9% (95% confidence interval [CI] 6.8–8.9%) and 57.2% (95% CI 45.1–48.8%), respectively. The following 14 risk factors had a significant association with frailty: at risk of malnutrition, sarcopenia, severe mobility limitation, poor social capital, rural dwellers, depressive, poor self-perceived health, polypharmacy, elevated high-sensitivity C-reactive protein, elevated glycosylated hemoglobin, low 25-hydroxy vitamin D level, longer timed up and go, and low short physical performance battery score (p<0.05). Physico-nutritional, psychological, sociodemographic, and medical factors are strongly associated with frailty.
Tue, 15 September 2020
REVIEW | doi:10.20944/preprints202009.0337.v1
Subject: Medicine & Pharmacology, Other Keywords: hand sanitizers; hand rubs; alcohol based; disinfection; hand hygiene; coronavirus; COVID-19
Online: 15 September 2020 (09:07:09 CEST)
The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.
ARTICLE | doi:10.20944/preprints202009.0335.v1
Subject: Medicine & Pharmacology, Other Keywords: active transportation; health impact assessment; physical activity; air pollution; traffic safety; carbon emissions; monetization; online tool
Online: 15 September 2020 (08:40:57 CEST)
The World Health Organization’s Health Economic Assessment Tool (HEAT) for walking and cycling is a user-friendly web-based tool to assess health impacts of active travel. HEAT, developed over 10 years ago, has been used by researchers, planners and policymakers alike in appraisals of walking and cycling policies of both national and more local scales. HEAT has undergone regular upgrades adopting the latest scientific evidence. This article presents the most recent upgrades of the tool. Health impacts of walking and/or cycling in a specified population are quantified in terms of premature deaths avoided (or caused). In addition to the calculation of benefits from physical activity, HEAT was recently expanded to include assessments of the burden associated with air pollution exposure and crash risks while walking or cycling. Further, impacts on carbon emissions from mode shift to active travel modes can now be assessed. Monetization of impacts using Value of Statistical Life and Social Costs of Carbon now uses country-specific values. As active travel inherently results in often substantial health benefits as well as not always negligible risks, assessments of active travel behaviour or policies are incomplete without considering health implications. The recent developments of HEAT make it easier than ever to obtain ballpark estimates of health impacts and carbon emissions related to walking and cycling.
Thu, 10 September 2020
BRIEF REPORT | doi:10.20944/preprints202009.0229.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; pneumonia; low-dose whole-lung irradiation; SpO2
Online: 10 September 2020 (08:36:57 CEST)
Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO2, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO2 upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO2 ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO2. Five patients were discharged (median 6th day, range 2nd-14th day), and four patients died (median 7th day, range 3rd-10th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.
Tue, 8 September 2020
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; zinc; zn; zinc-deficiency; cytokine storm
Online: 8 September 2020 (10:09:19 CEST)
Since the discovery of the first reported case with Zinc-deficiency in Iran1 by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response 2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency4. In the western world, Zinc deficiency is more prevalent among the geriatric population3, vegans/vegetarians, and people with certain underlying conditions4such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders4,5. Zinc and Zinc deficiency has been associated with several infectious diseases 2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21st century6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.
Fri, 4 September 2020
REVIEW | doi:10.20944/preprints202009.0103.v1
Subject: Medicine & Pharmacology, Other Keywords: climate change; vector-borne disease; artificial intelligence; explainable AI; geospatial modeling; infectious disease; arbovirus
Online: 4 September 2020 (12:21:32 CEST)
As recent history has shown, changing climate not only threatens to increase the spread of known disease, but also the emergence of new and dangerous phenotypes. This occurred most recently with West Nile virus: a virus previously known for mild febrile illness rapidly emerged to become a major cause of mortality and long-term disability throughout the world. As we move forward, into increasingly uncertain times, public health research must begin to incorporate a broader understanding of the determinants of disease emergence – what, how, why, and when. The increasing mainstream availability of high-quality open data and high-powered analytical methods presents promising new opportunities. Up to now, quantitative models of disease outbreak risk have been largely based on just a few key drivers, namely climate and large-scale climatic effects. Such limited assessments, however, often overlook key interacting processes and downstream determinants more likely to drive local manifestation of disease. Such pivotal determinants may include local host abundance, human behavioral variability, and population susceptibility dynamics. The results of such analyses can therefore be misleading in cases where necessary downstream requirements are not fulfilled. It is therefore important to develop models that include climate and higher-level climatic effects alongside the downstream non-climatic factors that ultimately determine individual disease manifestation. Today, few models attempt to comprehensively address such dynamics: up until very recently, the technology simply hasn’t been available. Herein, we present an updated overview of current perspectives on the varying drivers and levels of interactions that drive disease spread. We review the predominant analytical paradigms, discuss their strengths and weaknesses, and highlight promising new analytical solutions. Our focus is on the prediction of arboviruses, particularly West Nile virus, as these diseases represent the pinnacle of epidemiological complexity – solution to which would serve as an effective “gatekeeper”. We present the current state-of-the-art with respect to known drivers of arbovirus outbreak risk and severity, differentially highlighting the impact of climate and non-climatic drivers. The reality of multiple classes of drivers interacting at different geospatial and temporal scales requires advanced new methodologies. We therefore close out by presenting and discussing some promising new applications of AI. Given the reality of accelerating disease risks due to climate change, public health and other related fields must begin the process of updating their research programs to incorporate these much needed, new capabilities.
Thu, 3 September 2020
REVIEW | doi:10.20944/preprints202009.0067.v1
Online: 3 September 2020 (09:29:32 CEST)
Background: The reported associations between time to first antibiotic dose after hospital arrival and short-term mortality have varied in prior studies of CAP. It is unclear the benefit of early antibiotics in all patients given the risks of antibiotic overuse and misdiagnosis; Methods: A PubMed and Google Scholar search was performed to identify articles detailing the epidemiology, prognosis, diagnosis, and preliminary management of CAP; Results: In sepsis, antibiotics should not be delayed, and should be administered as soon as possible after recognition. For moderate or severe CAP patients without sepsis, antibiotics should be administered as soon as the diagnosis of CAP is highly likely. For stable, non–critically ill patients with CAP, the timing of antibiotics is not as clear and available evidence does not recommend strict requirements. Antibiotic timing – both rapid and delayed could be used as indicators of quality care in differing clinical scenarios; Results: The dogma of starting antibiotics quickly, within a rigid timeframe of expectations and guidelines has not improved outcomes in pneumonia patients, and has led to an increase in antibiotic treatment in uninfected patients. Severity of illness is the key factor associated with poor outcomes and should more significantly guide the timing of antibiotic initiation.
Wed, 2 September 2020
REVIEW | doi:10.20944/preprints202009.0030.v1
Subject: Medicine & Pharmacology, Other Keywords: multi-morbidity; CGA; frailty; polypharmacy; deprescribing
Online: 2 September 2020 (06:04:17 CEST)
Multi-morbidity and polypharmacy are common in older people and pose a challenge for health and social care systems especially in context of global population ageing. They are complex and interrelated concepts in the care of older people that require early detection and patient centred decision making that are underpinned by the principles of multidisciplinary led comprehensive geriatric assessment (CGA). Personalised care plans need to remain responsive and adaptable to the needs of a patient, enabling an individual to maintain their independence.
Tue, 1 September 2020
ARTICLE | doi:10.20944/preprints202009.0016.v1
Online: 1 September 2020 (12:07:42 CEST)
Law enforcement is an intermittently physically demanding job, interspersed with long periods of sedentary activity. To prepare for the physical demands of the job, law enforcement agencies enlist recruits into academies with a focus on physical training. Often academies focus on aerobic based exercise despite anaerobic fitness being strongly correlated to occupational tasks. The objective of this article is to analyse the changes in fitness of police recruits during academy training. Initial and final fitness test results, encompassing muscular power, strength, endurance as well as aerobic and anaerobic fitness, were measured to analyse changes in fitness. Dependent t-tests showed significant increases (p < 0.05) across all fitness tests, with a trend towards larger increases in aerobic and muscle endurance-based tests. Recruits from this academy tended to have higher fitness results compared to other academies and were either average or below average compared to age matched standards in the general populations. Physical training should persist for recruits beyond the academy to continue develop fitness throughout their career. Academies should add a focus on muscular strength and power training as these measures relate to occupational tasks, which may better prepare recruits for demands they will be expected to face in the field.
Sun, 30 August 2020
Subject: Medicine & Pharmacology, Other Keywords: Adolescent girls; Female genital mutilation/cutting; Global health; Sexual initiation; Sexual and reproductive health; Young women
Online: 30 August 2020 (17:28:36 CEST)
Despite several attempts by governments and non-governmental organizations to eliminate female genital mutilation or cutting, it is puzzling that this traditional procedure is widely practiced today in many parts of sub-Saharan Africa (SSA). Scholarly arguments on the influence of female genital mutilation on sexual behavior up until now remain inconclusive. The current study sought to examine the association between female genital mutilation and early sexual initiation among girls and young women (AGYW) in SSA. Data from Demographic and Health Surveys (DHS) of 12 SSA countries were combined. A total of 30,089 AGYW (15-24 years) who had ever had sex and had complete information on all the variables of interest were considered. The outcome variable for the study was early sexual initiation. The study employed multilevel logistic regression for the data analysis, with reported odds ratio and associated 95% confidence intervals (CIs). The overall prevalence of female genital mutilation among AGYW was 49.9%, with the highest and lowest prevalence in Guinea (95.8%) and Togo (3.3%) respectively. The prevalence of early sexual initiation was 42.4%, with the highest and lowest prevalence in Niger (59.9%) and Burkina Faso (30.6%) respectively. AGYW who had not experienced female genital mutilation were less likely to have early sexual initiation [OR= 0.74, CI= 0.70-0.78], compared to those who had experienced female genital mutilation, after controlling for significant covariates. The likelihood of early sexual initiation was high among AGYW aged 15-19 [OR=2.38, CI=2.26-2.51] but low among AGYW with secondary education [AOR=0.58, CI=0.54-0.63], those who had never married [OR=0.68, CI=0.60-0.78], those in households with richest wealth quintile [OR=0.64, CI=0.57-0.72], those who were exposed to mass media [OR=0.88, CI=0.83-0.93], and those working [OR=0.91, CI=0.87-0.96]. Not undergoing female genital mutilation in the midst of socio-economic factors (e.g., education level, household wealth) could limit AGYW from early sexual debut. These findings underscore the need for effective campaign and programs (e.g., educational programs, entrepreneurial training, micro-finance schemes) against the practice of female genital mutilation. Policy interventions (e.g., “schooling for the girl-child” initiatives) that might delay early sexual initiation among adolescent girls and young women in the midst of identified socio-economic factors should be developed.
REVIEW | doi:10.20944/preprints202008.0672.v1
Subject: Medicine & Pharmacology, Other Keywords: breakthrough invasive fungal infections; invasive candidiasis; invasive mold infections; endemic mycoses; diagnostics
Online: 30 August 2020 (15:13:51 CEST)
Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity of conventional culture techniques, serologic tests, and PCR-based assays in patients on antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.
Fri, 28 August 2020
CASE REPORT | doi:10.20944/preprints202008.0640.v1
Subject: Medicine & Pharmacology, Other Keywords: VIP; COVID-19; respiratory failure; vasoactive intestinal peptide; aviptadil; ARDS
Online: 28 August 2020 (11:38:23 CEST)
Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.
Wed, 26 August 2020
ARTICLE | doi:10.20944/preprints202008.0582.v1
Online: 26 August 2020 (10:59:37 CEST)
Background: Dimethylfumarate (DMF) is an orally administered fumaric acid esters (FAE) approved for plaque psoriasis. The most represented adverse event for incidence reported in all studies regarding multiple sclerosis and psoriasis treatment was flushing followed by gastrointestinal and lymphopenia (AEs). We report our experience on effective management strategies in patients with dimethylfumarate fushing induced. Methods: The purpose of our study is addressed to propose feasibles strategies able to mitigate adverse events developing in order to improve therapy compliance. We report our real life experience of 20 patients affected by mild to moderate plaque psoriasis in treatement with DMF 10 male and 10 female, with 45,4 years old mean age underwent to a reducing a daily dosage regimen with DMF from 120 mg to 30 mg tablets. Patients experience flushing around 30-45 minutes after assuming the medication.per day. Results: Patients achieving a good adherence and efficacious results in terms of PASI 75 reduction after 16 weeks of treatment. Conclusion: DMF is efficacious and has a favorable benefit–risk profile, thanks to the possibility of implementing posology strategies in order to optimize adherence to the therapy.
Mon, 24 August 2020
BRIEF REPORT | doi:10.20944/preprints202008.0519.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2, COVID-19, Acute Respiratory Distress Syndrome, ARDS, Famotidine, Celecoxib
Online: 24 August 2020 (09:46:15 CEST)
Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)1. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.
CASE REPORT | doi:10.20944/preprints202008.0502.v1
Subject: Medicine & Pharmacology, Other Keywords: KARS gene; aminoacylation; leucodistrophy; epilepsy; hearing loss developmental delay; whole exome sequencing
Online: 24 August 2020 (03:10:45 CEST)
The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS) which activates and joins the lysin with its corresponding transfer RNA (tRNA), through the ATP-dependent aminoacylation of the amino acid. The KARS gene mutations have been linked to diverse neurologic phenotypes such as: neurosensorial hearing loss, leukodistrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, impairment of the mitochondrial respiratory chain, hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene.
Sat, 22 August 2020
ARTICLE | doi:10.20944/preprints201905.0332.v2
Subject: Medicine & Pharmacology, Other Keywords: obesity; renal injury; lipocalin-2; collagen type IV; inflammation
Online: 22 August 2020 (03:56:22 CEST)
Rats fed a high-fat diet with a single streptozotocin (STZ) injection developed obesity, prediabetes, cardiac hypertrophy and diastolic dysfunction. Here we aimed to explore the renal consequences of prediabetes in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or high-fat diet containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 cardiac functions were examined (Koncsos et al., 2016) and blood and urine samples were taken. Kidney samples were collected for histology, immunohistochemistry and for analysis of gene expression. High-fat diet and streptozotocin increased body weight gain and visceral adiposity, and plasma leptin, elevated fasting blood glucose levels, impaired glucose and insulin tolerance, despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression and cortical and medullary mRNA expression of TGF-β1, Nrf2, PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while serum lipid and liver enzyme levels were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury.
Thu, 20 August 2020
ARTICLE | doi:10.20944/preprints202008.0422.v1
Subject: Medicine & Pharmacology, Other Keywords: telemedicine; COVID-19; telehealth; health service lines; pandemic
Online: 20 August 2020 (04:10:27 CEST)
Background – The profound impact of COVID-19 on the U.S. healthcare industry cannot be overstated. Telemedicine utilization exploded virtually overnight as healthcare systems, hospitals, and clinical practices rushed to implement this delivery model to ensure accessibility and continuity of patient care access across myriad service lines and dimensions. Objective – The purpose of this systematic literature review is to examine the measures that were implemented to accommodate community and individual patient needs not only to afford access to critical services, but to also maintain safety standards for affected parties. Methods – Boolean operators were crafted with the expressed intent of identifying articles within multiple database domains germane to our chosen topic. Results – 52,206 articles were captured from a general search query and subsequently distilled to 44 through group consensus based on pertinence to our basic research question. The four health service lines identified encountered similar, surmountable obstacles in their care delivery models, but adapted accordingly to the respective needs of their patient populations. Conclusion – This review showcased the healthcare industry’s ability to rapidly acclimate and change due to the pervasive spread of COVID-19 throughout the U.S. Although imperfect, unique responses were developed within telemedicine platforms to broadly and effectively mitigate disruptions in care and treatment modalities.
Tue, 18 August 2020
ARTICLE | doi:10.20944/preprints202008.0390.v1
Online: 18 August 2020 (12:07:32 CEST)
Background: Ongoing Primary and Secondary Education Development Program (PEDP & SEDP) has led to increase in enrollment of children in schools. This created a high demand for facilities such as classroom, chairs, laboratories, latrines and water supply. Water and latrines did not receive equal attention like others. National strategic plan for School Water Sanitation and Hygiene (SWASH) 2012-2017 was to address such challenges with objectives to improve SWASH by 2017. Hence this study aimed to evaluate the implementation of SWASH program in Ukerewe. Methodology: A cross sectional survey was done among 42 schools in the district with 40 schools being government owned. Systematic random sampling was used and data were collected using a structured interview which was pre-tested and amended prior to conducting fieldwork. UNICEF, WASH in Schools Monitoring Package observational check-list was used to assess sanitation facilities. Results: Findings from this study showed the latrine-hole to student ratio was 1:71 with only 31.3% of the latrines being in good clean condition and about half (59.5%) of the schools have no facilities for washing hands. For the schools with hand washing facilities only 21.4% have an effective hand washing practice (presence of soap and water). The most common source of water used was lake water (35.7%) with (42.9%) having water storage facilities. Conclusion: The study shows that most of the objectives of national strategic plan are yet to be implemented at Ukerewe. There is a need for minor repairs to complete new construction of SWASH facilities in Ukerewe.
ARTICLE | doi:10.20944/preprints202008.0381.v1
Subject: Medicine & Pharmacology, Other Keywords: continuous quality improvement; healthcare sector; biology risk control; patient safety; research to practice
Online: 18 August 2020 (10:57:11 CEST)
Stakeholder input into the decision-making process when developing public health programs and policies is crucial. This article presents an innovative approach, involving online participation with a wide group of stakeholders located in different geographic locations, for policy consensus by research methodology. The results of the project have been used to propose assumptions regarding a strategy for preventing blood-borne diseases in Poland. The research was conducted iteratively using a multi-stage qualitative methodology to explore risk assessment involving blood-borne infections. The final output of the entire project is a list of key problems/challenges and solutions associated with medical and nonmedical services that are connected to the breakage of tissue continuity. Qualitative research is rare in risk assessment as priority is usually given to statistical data and end-points (quantitative studies ). Statistical data on health risk allows to assess the health implications, while the methodology applied also allowed diagnosis of the processes leading to these effects. In addition to policy preparation for blood-borne illnesses, the methodology employed in the study can also be used to successfully explore other areas of public health policy decisions.
Fri, 14 August 2020
REVIEW | doi:10.20944/preprints202008.0311.v1
Online: 14 August 2020 (08:15:09 CEST)
Prevalence of overweight and obesity are escalating globally among the general population. However, there are limited evidence on the trends and prevalence of overweight /obesity in the military setting. Increased rates of injuries, low work productivity, incurred higher healthcare costs and prematurely discharge from service are consequences of overweight/obesity among the military. Therefore, we aimed to systematically describe the trends and prevalence of overweight and obesity in the military population, by regions and military service branches. Databases including PubMed, Scopus, Web of Science and Google Scholar were used. Inclusion criteria were military population (inclusive of all service branches) with BMI reported as the overweight/obesity indicator. Population related to military but not exclusively military personnel such as the retirees, the veterans and their dependents were excluded. From the 27 included studies, 13 were published between year 2010 to 2014 and half were conducted in the United States. Overall, studies showed increasing trend in the prevalence of overweight (30% to 50%) and obesity (2% to 30%); only one study showed a decreasing trend of 0.9% and 0.6% for the prevalence of overweight and obesity respectively. However, the rates of increment differed between countries, where Asian countries demonstrated lower overweight prevalence compared to the United States and the European countries. In conclusion, the military population is not protected from overweight and obesity. Interventions should be implemented to prevent overweight / obesity among the military personnel.
Sat, 8 August 2020
ARTICLE | doi:10.20944/preprints202008.0204.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-Cov-2; epidemic surveillance; emerging infectious disease; epidemic threshold
Online: 8 August 2020 (04:25:20 CEST)
Background: Understanding the SARS-CoV-2 dynamics and transmission is a major issue to model and control its propagation. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidences from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services and the review of medical biology laboratory data. We also check the role played in the virus propagation by a large religious meeting which gathered over 2000 participants from all over France mid-February in Mulhouse. Results: SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26th 2020 and the sanitary alert on March 3rd. The religious gathering played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak which was in place much earlier. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.
Thu, 6 August 2020
ARTICLE | doi:10.20944/preprints202008.0143.v1
Subject: Medicine & Pharmacology, Other Keywords: chronic kidney disease; low socioeconomic status; mortality
Online: 6 August 2020 (09:46:30 CEST)
Background: To examine the association between income levels and mortality rates in patients with chronic kidney disease. Methods: We analyzed data obtained from 3,172 patients with chronic kidney disease obtained from the Korean National Health Insurance claims database (2003–2009). Each patient was monitored until December 2010 or until death, whichever came first. Individual income was estimated from the national health insurance premium. Information on mortality was obtained from the Korean National Statistical Office. Cox proportional hazard models were used to compare mortality rates between different income groups after adjusting for possible confounding risk factors. Results: A low income was significantly associated with a high mortality rate after adjusting for covariates (adjusted HR 1.298 [1.082–1.556]). In addition, dialysis patients who had low incomes were more likely to have higher mortality rates compared to those in dialysis patients who had high incomes (adjusted HR 1.528 [1.122–2.082]). Conclusion: The findings of this study indicate that chronic kidney disease patients with low incomes have the highest mortality risk. Promotion of targeted policies and priority health services for patients with low incomes may help reduce the mortality rate in this vulnerable group.
Wed, 5 August 2020
ARTICLE | doi:10.20944/preprints202008.0130.v1
Subject: Medicine & Pharmacology, Other Keywords: antioxidant; C2C12 cell; Jakyakgamcho-tang; muscle atrophy; oxidative stress
Online: 5 August 2020 (10:43:24 CEST)
Oxidative stress is a major contributor to muscle aging and loss of muscle tissue. Jakyakgamcho-tang has been used in traditional Eastern medicine to treat muscle pain. Here, we compared various solvent-based Jakyakgamcho-tang extracts in terms of their effects against hydrogen peroxide-induced oxidative stress in murine C2C12 skeletal muscle cells. Total phenolic content and total flavonoid content in 30% ethanol extracts of Jakyakgamcho-tang were higher than those of water extracts of Jakyakgamcho-tang. Ethanol extracts of Jakyakgamcho-tang had stronger antioxidant and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and 2,2´-diphenyl-1-picrylhydrazyl-scavenging activity than water extracts of Jakyakgamcho-tang. The ethanol extract of Jakyakgamcho-tang inhibited peroxide-induced cell viability and intracellular reactive oxygen species generation more effectively than the water extract of Jakyakgamcho-tang in a dose-dependent manner. These results suggest that the ethanol extract of Jakyakgamcho-tang is relatively more efficacious at protecting against oxidative stress-induced muscle cell death because it prevents reactive oxygen species generation in C2C12 cells. Moreover, the current study indicated that the effective dose of the ethanol extract of Jakyakgamcho-tang required to alleviate muscle pain might be lower than that required for Jakyakgamcho-tang.
REVIEW | doi:10.20944/preprints202007.0137.v2
Subject: Medicine & Pharmacology, Other Keywords: Lysosomal Storage Disorders; GM2 gangliosidoses; Tay-Sachs disease; Sandhoff disease; β-Hexosaminidases; Therapeutic alternatives
Online: 5 August 2020 (05:05:13 CEST)
GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay-Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood-brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g. intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.
Sun, 2 August 2020
REVIEW | doi:10.20944/preprints202008.0035.v1
Subject: Medicine & Pharmacology, Other Keywords: Experimental radiotherapy; radiobiology; Mesenchymal stem cells; Cell therapy; Exosome; Annexin A1; Acute-respiratory-distress-syndrome; COVID-19
Online: 2 August 2020 (14:54:24 CEST)
Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.
Fri, 31 July 2020
ARTICLE | doi:10.20944/preprints202007.0740.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Virus Detection; Viral Diagnostics; Diagnostics; SARS-CoV-2; Coronavirus; PCR
Online: 31 July 2020 (09:31:18 CEST)
Accurate and timely testing has become an essential measure in combatting the COVID-19 global pandemic. Currently, polymerase chain reaction (PCR) based assays are the most relied on methods for SARS-CoV-2 detection. This traditional workflow involves a viral RNA extraction from the viral transport media storing nasopharyngeal swabs collected from patients, followed by PCR based detection. While accurate, this methodology is time consuming and resource heavy, causing for delays in receiving results or limited access to testing. Herein, we demonstrate a validated method for SARS-CoV-2 detection from viral transport media using a two-step, direct-to-PCR workflow revolving around shaker-mill homogenization. This method completely bypasses the extraction steps of the traditional workflow, replacing it with 30 seconds of mechanical disruption sufficient to allow for COVID-19 detection with a 96.43% sensitivity and 100% specificity when compared to traditional extraction to PCR based methods.
Sat, 25 July 2020
ARTICLE | doi:10.20944/preprints202007.0621.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19; mortality; epidemiology; risk factors; Nigeria; Africa
Online: 25 July 2020 (18:20:23 CEST)
Nigeria is the most populous country in the African continent. The aim of this study was to analyze risk factors for COVID-19 prevalence and deaths in all 6 geopolitical regions and 37 states in Nigeria. We analyzed the data retrieved from various sources, including Nigeria CDC, Nigeria National Bureau of Statistics, Unicef-Nigeria multiple indicator cluster survey and the Institute of Health Metrics and Evaluation, University of Washington. We examined 4 clinical risk factors (prevalence of TB, HIV, smoking and BCG vaccination coverage) and 5 sociodemographic factors (age ≥65, population density, literacy rate, unemployment and GDP per capita). Multivariate modeling was conducted using generalized linear model. Our analysis showed that the incidence of confirmed COVID-19 cases differed widely across the 37 states, from 0.09 per 100,000 in Kogi to 83.7 in Lagos. However, more than 70% of confirmed cases were concentrated in just 7 states: Lagos, Abuja, Oyo, Kano, Edo, Rivers and Delta. Case mortality rate (CMR) per million population also varied considerably, with Lagos, Abuja and Edo having CMR above 9. On bivariate analysis, higher CMR correlated positively with GDP and to a lesser extent with TB and population density. On multivariate analysis, which is more definitive, states with higher HIV prevalence and BCG coverage had lower CMR, while high GDP states had a greater CMR. This study indicates that COVID-19 has disproportionately affected certain states in Nigeria. Population susceptibility factors include higher economic development but not literacy or unemployment. Death rates were mildly lower in states with higher HIV prevalence and BCG vaccination coverage.
Fri, 24 July 2020
ARTICLE | doi:10.20944/preprints202007.0596.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-CoV-2; immunity; T cells; IL-6; GGT; hepatopathy; biliary lesion; acute kidney injury; liver disease
Online: 24 July 2020 (14:40:42 CEST)
The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.
Wed, 22 July 2020
REVIEW | doi:10.20944/preprints202007.0516.v1
Subject: Medicine & Pharmacology, Other Keywords: Megakaryocyte, IFITM3, VWF, ADAMTS13, emperipolesis, self-association, unfractionated heparin (UFH), histone, NETs, Thrombin
Online: 22 July 2020 (11:03:08 CEST)
COVID-19 thromboembolic disease has brought all of us back to the drawing board. In COVID-19, pre-existing activated endothelium with increased Von Willebrand factor (VWF), low density lipoprotein (LDL) promoting “self-association” and “sticking” of long VWF strings to the vascular endothelial wall, suppressed ADAMTS13 cleavage of VWF, hypoxia induced upregulation and activation of VWF, fibrous network from neutrophil extracellular traps (NETs) with free DNA and histone, all appear to be initiating the thrombogenesis. Worsening complement activation, cytokine storm and resulting endothelial destruction, unregulated thrombogenesis leads to vascular occlusions and hypoxia. At this stage, the presence of abundant extracellular DNA, histone and -defensins appears worse than the SARS-CoV-2 itself. Previously observed in vitro mechanisms like histone “auto-activating” prothrombin, histone activated platelets generating thrombin without FXII, thrombin and plasmin cleaving complement C5 appears highly likely in COVID-19. Megakaryocytes are actively producing platelets in the lungs and appear to play a major role in thrombogenesis of COVID-19 raising suspicion of emperipolesis. This focused review is a compilation of my observations in relation to the pathophysiology of the intravascular environment, mainly in COVID-19 lungs. Pathophysiology based clinical trials are paramount in reducing morbidity and mortality in COVID-19.
ARTICLE | doi:10.20944/preprints202007.0508.v1
Subject: Medicine & Pharmacology, Other Keywords: Angiotensin-II Type-I receptor; renin-angiotensin system; valsartan; colorectal cancer
Online: 22 July 2020 (09:49:51 CEST)
Dysregulation of the angiotensin-II Type-I receptor (AT1R) and its pathway was reported to associate with poor-prognosis in several malignancies, including colorectal-cancer (CRC). We have explored the therapeutic-potential of targeting AT1R using valsartan, and its pharmacological-interaction with Fluorouracil (5-FU) in CRC. Anti-proliferative function was evaluated in 2-/3-dimensional cells and in vivo models. Anti-proliferative, anti-migratory, apoptotic function and effect on cell-cycle was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing test, and Fluorescence-activated cell sorting (FACS), respectively, while gene-expression was determined at mRNA/protein levels. By histogical analysis and measuring of oxidative/antioxidant markers, we evaluated the anti-inflammatory properties of valsartan. Valsartan suppressed cell-growth and impacted the anti-tumor-activities of 5-FU by apoptosis-induction. Valsartan inhibited the cells migration by perturbation of Matrix metalloproteinase (MMP1). Furthermore, valsartan inhibited tumor-growth and metastasis, and this was more notable in valsartan/5-FU combination-treated-group. The mechanism was plausible to be via the induction of Reactive-oxygen-species (ROS) and down-regulation of Superoxide-dismutase (SOD), thiol/catalase (CAT) as well as Vascular endothelial growth factor (VEGF) and Transforming growth factor beta (TGF-β). Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory components include fibronectin, Interleukin) IL-1β (, Tumor necrosis factor alpha) TNF-α (, Interferon gamma) INF-γ (, and Monocyte Chemotactic Protein 1 (MCP-1). Our findings demonstrated that targeting the AT1R receptor may inhibit tumor-growth and ameliorate fibrosis and inflammation associated with CRC via modulation of AT1 and TGF-β pathways.
Subject: Medicine & Pharmacology, Other Keywords: Xerostomia; Dry mouth; Salivary hypofunction; Saliva
Online: 22 July 2020 (09:44:12 CEST)
Xerostomia is a subjective symptom of dry mouth resulting from various causes, including side effects of medication, systemic disorders, radiation, and Sjögren’s syndrome. Recently, the number of patients afflicted with xerostomia has increased due to an increase in the elderly population and patients on medication.; (2) Methods: A systematic approach is required to determine the etiology and management of xerostomia. This review summarizes recent literatures on the diagnosis and management of xerostomia.; (3) Results: A patient with xerostomia experiences difficulty in chewing, swallowing, speaking, tasting, and maintaining oral hygiene. Xerostomia and hyposalivation are uncomfortable side-effects in many patients. Assessing the function of the salivary gland is essential for selecting an appropriate treatment, improving symptoms, and preventing oral complications. Also, a more systematic approach is required to differentiate the subjective symptoms of the patient from the objective hyposalivation.; and (4) Conclusions: Although there is no standardized treatment for xerostomia, doctors need to endeavor and adapt the various treatments of xerostomia, to unearth the optimal treatment required for the patient.
Mon, 20 July 2020
REVIEW | doi:10.20944/preprints202007.0465.v1
Subject: Medicine & Pharmacology, Other Keywords: laboratory-acquired brucellosis; prevention; biosafety; cultures; identification; biochemical tests; MALDI-TOF; FISH; laboratory-acquired brucellosis; prevention; biosafety; cultures; identification; biochemical tests; MALDI-TOF; FISH
Online: 20 July 2020 (09:38:57 CEST)
Brucellosis is one of the most common etiologies of laboratory-acquired infections worldwide, and handling of living brucellae should be performed in a Class II biological safety cabinet. The low infecting dose, multiple portals of entry to the body, the great variety of potentially contaminated specimens, and the unspecific clinical manifestations of human infections facilitate the unintentional transmission of brucellae to laboratory personnel. Work accidents such as spillage of culture media cause only a small minority of exposures, whereas >80% of events result from unfamiliarity with the phenotypic features of the genus, misidentification of isolates, and unsafe laboratory practices such as aerosolization of bacteria and working on an open bench without protective goggles or gloves. Although the bacteriological diagnosis of brucellae by traditional methods is simple, the Gram stain and the biochemical profile of the organism, as determined by commercial kits, can be misleading, resulting in inadvertent exposure and contagion. The use of novel identification technologies is not hazard-free. The MALDI-TOF technology requires an initial bacterial inactivation step, while the instruments’ reference database may misidentify Brucella as belonging to other Gram-negative species. The rapid identification by the FISH method mistakes brucellar isolates for members of the closely related Ochrobactrum genus.
Sun, 19 July 2020
ARTICLE | doi:10.20944/preprints202007.0408.v1
Subject: Medicine & Pharmacology, Other Keywords: Wharton’s Jelly human umbilical cord mesenchymal stem cells (hWJ-MSCs); Growth Differentiation Factor-5; human bone marrow Mesenchymal Stem Cells (hBM-MSCs); tenogenic commitment; gene expression; immunofluorescence assay
Online: 19 July 2020 (11:02:01 CEST)
Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.
Fri, 17 July 2020
ARTICLE | doi:10.20944/preprints202007.0384.v1
Subject: Medicine & Pharmacology, Other Keywords: neuromuscular disorders; dynamic arm support; activity monitoring; motor performance
Online: 17 July 2020 (14:17:28 CEST)
Neuromuscular disorders cause progressive muscular weakness, which limits upper extremity mobility and performance during activities of daily life. A dynamic arm support can improve mobility and quality of life. However, their use is often discontinued over time for unclear reasons. This study aimed to evaluate whether users of dynamic arm supports demonstrate and perceive quantifiable mobility benefits over a period of two months. Nine users of dynamic arm supports were included in this observational study. They had different neuromuscular disorders and collectively used four different arm supports. They were observed for three consecutive weeks during which they were equipped with a multi-sensor network of accelerometers to assess the actual use of the arm support and they were asked to provide self-reports on the perceived benefits of the devices. Benefits were experienced mainly during anti-gravity activities and the measured use did not change over time. The self-reports provided contextual information in domains such as participation to social life, in addition to the sensor system. However self-reports overestimated the actual use by up to three-fold compared to the accelerometer measures. A combination of objective and subjective methods is recommended for meaningful and quantifiable mobility benefits during activities of daily life.
REVIEW | doi:10.20944/preprints202007.0375.v1
Subject: Medicine & Pharmacology, Other Keywords: bacterial infection; non-healing wounds; antimicrobial resistance; multidrug resistance; antimicrobial peptides (AMPs); AMP conjugates; AMP carriers and delivery systems
Online: 17 July 2020 (09:26:21 CEST)
Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.
ARTICLE | doi:10.20944/preprints202007.0367.v1
Subject: Medicine & Pharmacology, Other Keywords: Confirmed cases, case fatality rate, province, age, gender.
Online: 17 July 2020 (06:24:55 CEST)
The initial outbreak of COVID-19 was first reported in Wuhan (China) during the latter part of December 2019. Indonesia has the fourth-largest population globally and reported the country’s first case of the virus on 2nd March 2020. The World Health Organisation (WHO) in addition to several neighbouring provinces and educational institutions within the region began questioning the Indonesian government upon the initial case reported. The objective of this study was to describe the epidemiological characteristics of the COVID-19 outbreak in Indonesia during March 2020. The data were collected from Indonesian government databases and non-government organisations (NGOs). The data were analysed using Microsoft Office 2019 (Excel) and Adobe Illustrator 2017 software, was used in drawing the map depicting the distribution of COVID-19 in Indonesia. As at 31st March 2020, a total of 1,528 people in Indonesia have been infected by COVID-19, in addition to 136 mortalities (CFR of 8.9%). Jakarta, as the principal capital of Indonesia, quickly has become the epicentre of the virus since this period. Most patient cases were attributed to those aged between 31 and 70 years (72.64%), with male patients (64.93%) representing the highest incidence of cases compared to female patients (35.07%). The number of ventilating machines was 3,326, with hospital numbers at 859. The distribution of cases depicting COVID-19 was mainly seen in urban areas compared to rural areas. Males compared to females, are at a higher risk of contracting COVID-19, including those aged below 30, between 30 and 60 or above. Indonesia also has the highest case fatality rate (CFR) with respect to mortalities in Southeast Asia and has the second-highest CFR globally. Similarly, while the number of ventilator machines as at 31st March 2020 were sufficient in meeting the growing number of COVID-19 cases in the country, it is possible that the government may need to increase the number of ventilators if the cases continue to escalate.
Wed, 15 July 2020
REVIEW | doi:10.20944/preprints202005.0385.v2
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Thrombosis; Inflammation; ADAMTS13; Von Willebrand Factor
Online: 15 July 2020 (03:36:29 CEST)
Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral or fungal infections are well recognized to activate the coagulation system, COVID-19 associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. Von Willebrand Factor (VWF) and its protease, ADAMTS13 play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS13 has been reported. Also, an imbalance between ADAMTS13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment and improve clinical prognosis.
Tue, 14 July 2020
Subject: Medicine & Pharmacology, Other Keywords: Pharmacist; Community; Urinary tract infections; Leaflet; Self-care; General Public; Antimicrobial stewardship
Online: 14 July 2020 (10:53:34 CEST)
Community pharmacists are involved in antimicrobial stewardship through self-care advice and delivering medications for uncomplicated infections. Objectives This mixed methods study aimed to identify opportunities to enhance the role of community pharmacists in the management of patients with suspected or confirmed urinary tract infection (UTI). Methods Data collection was through a service user survey (n=51) and pharmacist surveys and semi-structured interviews before (16 interviews, 22 questionnaires) and after (15 interviews, 16 questionnaires) trialling UTI leaflets designed to be shared with patients. Data were analysed inductively using thematic analysis and descriptive tabulation of quantitative data. Results Twenty-five percent (n=13/51) of service users with urinary symptoms sought help from a pharmacist first and 65% (n=33/51) were comfortable discussing their urinary symptoms with a pharmacist in a private space. Community pharmacists were confident as the first professional contact for service users with uncomplicated UTI (n=13/16, 81%), but indicated the lack of a specific patient referral pathway (n=16/16, 100%), the need for additional funding and staff (n=10/16, 62%), and the importance of developing prescription options for pharmacists (5/16, 31%). All community pharmacists reported playing a daily role in controlling antimicrobial resistance by educating service users about viral and bacterial infections and promoting a healthy lifestyle. Enhancing their role will need greater integrated working with general practices and more prescribers based in community pharmacy. Conclusion This study suggests that community pharmacists could play a greater role in the management of uncomplicated UTI. The current reconfiguration of primary care in England with primary care networks and integrated care systems could provide a real opportunity for this collaborative working with potential learning for international initiatives.
REVIEW | doi:10.20944/preprints202007.0284.v1
Subject: Medicine & Pharmacology, Other Keywords: seaweed; sulfated polysaccharides; alginates; fucoidans; carrageenans; ulvans; wound dressing; wounds
Online: 14 July 2020 (03:37:56 CEST)
Wound healing involves a complex cascade of cellular, molecular, and biochemical responses and signaling processes. It consists of successive interrelated phases, the duration of which depends on multifactorial processes. Wound treatment is a major healthcare issue that can be resolved by development of effective and affordable wound dressings based on natural materials and biologically active substances. Proper use of modern wound dressings can significantly accelerate wound healing with minimal cosmetic defects. The innovative biotechnologies for creating modern natural interactive dressings are based on sulfated polysaccharides from seaweeds with their unique structures and biological properties, the availability of their sources in the form of wild bushes, and in the form of aquaculture, as well as with a high potential for participation in process control wound healing. These natural biopolymers are a novel and promising biologically active source for designing wound dressings based on alginates, fucoidans, carrageenans, and ulvans, which serve as active and effective therapeutic tools. The aim of this review is to summarize available information about the modern wound dressing’s technologies based on seaweed-derived polysaccharides, including those successfully implemented in commercial products, with the emphasis on promising and innovative designs. The further prospect of using marine biopolymers is related to the need to analyze the results of numerous in vitro and in vivo experiments, summarize clinical trial data, develop a scientifically based approach and relevant practical recommendations for the treatment of wounds.
Thu, 9 July 2020
ARTICLE | doi:10.20944/preprints202005.0431.v2
Subject: Medicine & Pharmacology, Other Keywords: Hip fracture; Casemix; Validation; Discrimination; Risk score; Calibration
Online: 9 July 2020 (17:23:04 CEST)
Objectives Independent validation of risk scores after hip fracture is uncommon, particularly for evaluation of outcomes other than death. We aimed to assess the Nottingham Hip Fracture Score (NHFS) for prediction of mortality, physical function, length of stay and postoperative complications. Design Analysis of routinely collected prospective data partly collected by follow-up interviews. Setting and Participants Consecutive hip fracture patients were identified from the Northumbria hip fracture database between 2014-2018. Patients were excluded if they were not surgically managed or if scores for predictive variables were missing. Methods C-statistics were calculated to test the discriminant ability of the NHFS, Abbreviated Mental Test Score (AMTS), and ASA grade for in-hospital, 30- and 120-day mortality, functional independence at discharge, 30-days and 120-days, length of stay, and postoperative complications. Results We analysed data from 3208 individuals, mean age 82.6 (SD 8.6). 2192 (70.9%) were female. 194 (6.3%) died during the first 30-days, 1686 (54.5%) were discharged to their own home, 211 (6.8%) had no mobility at 120-days, 141 (4.6%) experienced a postoperative complication. The median length of stay was 18 days (IQR 8-28). For mortality, c-statistics for the NHFS ranged from 0.68-0.69, similar to ASA and AMTS. For postoperative mobility, the c-statistics for the NHFS ranged from 0.74-0.83, similar to AMTS (0.61-0.82) and better than the ASA grade (0.68-0.71). Length of stay was significantly correlated with each score (p<0.001 by Jonckheere-Terpstra test); NHFS and AMTS showed inverted U-shaped relationships with length of stay. For postoperative complications, c-statistics for NHFS (0.54-0.59) were similar to ASA grade (0.53-0.61) and AMTS (0.50-0.58). Conclusions and Implications The NHFS performed consistently well in predicting functional outcomes, moderately in predicting mortality, but less well in predicting length of stay and complications. There remains room for improvement by adding further predictors such as measures of physical performance in future analyses.
ARTICLE | doi:10.20944/preprints202007.0189.v1
Online: 9 July 2020 (12:18:46 CEST)
Background: The novel emerging virus SARS-CoV-2 has affected all human-kind during the first half of 2020. The aim of the study was to survey the actual circumstances from January until May. Methods: The data are collected and released systematically, by law, from the National Epidemiological Surveillance of Infectious Disease (NESID). Findings: Analysis of these data revealed that the infection spread in Japan from late March to early April 2020. The SARS-CoV-2 infection rate at its peak was estimated to be 10%. Thus, the size of the population who may have been exposed to the novel virus in Japan is estimated at 0.2 million, which is relatively small. The number of related deaths is likely to converge on 1,000 people. Interpretation: Applying the law of large numbers allows estimation of the infection rate as well as of the size of the affected population by statistical analysis. How to collect the data must be defined before the data analysis is suggested to be important to reflect the actual circumstances about COVID-19.
ARTICLE | doi:10.20944/preprints202007.0186.v1
Subject: Medicine & Pharmacology, Other Keywords: infectious diseases; epidemics; dynamical modeling; COVID-19; first-order systems
Online: 9 July 2020 (12:08:34 CEST)
The semi-logarithmic plot of the cumulative number of cases of epidemics resembles the response of a first-order systems for a step load. This similarity was utilized to develop a first order model that can be used for extracting information about the dynamics of infectious disease epidemics. The developed model was validated using COVID-19 data of China. It was also heuristically fitted to other 13 countries. Obtained results indicated that the model can reliably forecasts the number of infected person, epidemic growth speed towards steady-state condition (process time constant, T), and time to reach steady-state condition (4T). The developed model will help public health authorities in developing more effective control strategies of epidemics.
REVIEW | doi:10.20944/preprints202007.0181.v1
Online: 9 July 2020 (10:49:11 CEST)
Given the pace of SARS-CoV-2 transmission and its relatively high mortality rate, COVID-19, has the potential to become the most severe pandemic in recent times. This virus’s spread across international borders has triggered different responses in countries around the globe with a spectrum of mild, moderate to severe outcomes. Nigeria, Africa’s most populous country with many densely populated cities, presents a unique situation for the explosive spread of SARS-CoV-2. However, at the point of this writing, the number of reported confirmed infection and mortality is comparatively lower to other countries with dense urban populations. The exact reasons for this are not clear but include societal, political and infrastructural factors that will influence the course of the outbreak in Nigeria. In this perspective, we have described the ongoing COVID-19 outbreak and its associated peculiarities. We identify critical steps that remain to be taken to contain and control the outbreak in Nigeria.
ARTICLE | doi:10.20944/preprints202007.0180.v1
Subject: Medicine & Pharmacology, Other Keywords: Cationic cyclodextrin; cyclodextrin polymer; epichlorohydrin cross-linker; nasal delivery; cytotoxicity; cell uptake
Online: 9 July 2020 (08:05:35 CEST)
Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.
Tue, 7 July 2020
REVIEW | doi:10.20944/preprints202007.0137.v1
Subject: Medicine & Pharmacology, Other Keywords: Lysosomal Storage Disorders; GM2 gangliosidosis; Tay-Sachs disease; Sandhoff disease; β-Hexosaminidases; Therapeutic alternatives
Online: 7 July 2020 (17:35:24 CEST)
GM2 gangliosidosis are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidosis have been described: Tay-Sachs disease, Sandhoff disease, and AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidosis patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidosis, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood-brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g. intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidosis, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.
ARTICLE | doi:10.20944/preprints202007.0122.v1
Subject: Medicine & Pharmacology, Other Keywords: Transcriptionally controlled tumor protein (TCTP); Tryptophan; Florescence; Flavonoid; Native gel electrophoresis
Online: 7 July 2020 (09:49:17 CEST)
Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.
Sun, 5 July 2020
REVIEW | doi:10.20944/preprints202007.0079.v1
Subject: Medicine & Pharmacology, Other Keywords: animal models; experimental models; SARS-CoV-2; COVID-19; rhesus macaque; monkey; hamster; ferrets; transgenic mice
Online: 5 July 2020 (15:07:53 CEST)
Background: The use of animal models for biomedical research provides us with a convenient and feasible route to establish causal relationships by recapitulating the temporal sequence of events in a controlled environment with a potential to manipulate the variables at multiple levels including genetic, protein, physiological or environmental. Objectives: The current review was conducted to gain insights into various animal models for the SARS-CoV-2 virus. Material and Methods: A literature review (PUBMED, PUBMED Central, PMC, Google Scholar, Google search engine) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in early April 2020 revealed 9 articles of interest. Search terms included covid 19, covid-19, novel corona virus, SARS-CoV-2, animal models, experimental models, laboratory models & covid 19 animal models. Two independent reviewers extracted the data; the third reviewer was involved in case of discrepancy. Results: SARS-CoV-2 shares an identical receptor binding domain with the SARS-CoV virus and has a superior binding affinity to the host ACE2. Based on this, the role of rhesus macaques, golden Syrian hamsters, transgenic hACE2 mice and ferrets as animal models have been studied. All four animals are susceptible to infection with SARS-CoV-2 with variable clinical presentation but universal recovery. The respiratory tract is primarily involved in all four models. Involvement of intestines was also seen in at least one study in each animal. Transfer to naïve animals in close contact has been documented in case of hamsters and ferrets. Seroconversion was documented in all although the role of convalescent sera was tested in hamsters only, with positive results though. Air-borne transmission was documented in ferrets and the possibility of feco-oral transmission was suggested for hamsters. The possibilities of recurrence and re-infection were ruled out by experiments upon the rhesus macaques. The fulfilment of Koch’s postulates has been highlighted. Discussion: The various studies available on animal models have been able to establish models of infection and transmission that recapitulate different aspects of disease in humans. However, the response between different animals and the same animal in different experiments is not completely coherent. Some of them do not manifest the disease clinically while others behave differently at molecular and immunological levels. Moreover, the physiology of these animals is not identical to human beings and the findings may not be extrapolated to human beings in an ‘as-is’ manner. Conclusions: The review acknowledges the achievements made by these experiments in a short span of time and highlighted the urgent need for a deeper dive in search of a quintessential animal model which can be studied for efficacy and safety of newer drugs and vaccines before a make-shift from the petri-dish to the human body can be contemplated.
ARTICLE | doi:10.20944/preprints202007.0050.v1
Subject: Medicine & Pharmacology, Other Keywords: positive deviance; dual-method use; contraception; unintended pregnancy; sexually transmitted infection; HIV/AIDS
Online: 5 July 2020 (07:04:27 CEST)
Dual-method use is the most reliable form of protection against unintended pregnancies and HIV/STIs. Although dual-method use remains uncommon among women in stable relationships, some women do practice it. In this study, we explored the barriers that make dual-method use rare and the behaviors of women who practice dual-method use using a positive deviance framework in Uganda. We screened 150 women using highly effective contraceptives at five health facilities. We identified nine women who practiced dual-method use and 141 women who did not. In a qualitative study, we conducted in-depth interviews with all nine women practicing dual-method use and 10 women randomly selected out of the 141 who did not. We performed a thematic analysis using the positive deviance framework. Regardless of practicing dual-method use or not, women faced perceived barriers against dual-method use, such as partner’s objection, distrust, shyness about introducing condoms into marital relationships, and limited access to condoms. However, women practicing dual-method use had higher levels of risk perception about unintended pregnancies and HIV/STIs. They also engaged in unique behaviors, such as influencing their partners’ condom use by initiating discussions, educating their partners on sexual risks and condom use, and obtaining condoms by themselves. These findings will be useful in developing effective community-led and peer-based interventions promoting dual-method use to reduce the dual burden of unintended pregnancies and HIV/STIs among women in Uganda.
Fri, 3 July 2020
ARTICLE | doi:10.20944/preprints202007.0036.v1
Subject: Medicine & Pharmacology, Other Keywords: patient engagement; stakeholder engagement; patient group engagement; prioritization tool; patient engagement activities
Online: 3 July 2020 (12:15:23 CEST)
Patient group engagement is increasingly used to inform the design, conduct, and dissemination of clinical trials and other medical research activities. However, the priorities of industry sponsors and patient groups differ, and there is currently no framework to help these groups identify mutually beneficial engagement activities. Methods: We conducted 28 qualitative, semi-structured interviews with representatives from research sponsor organizations (n=14) and patient groups (n=14) to determine: 1) how representatives define benefits and investments of patient group engagement in medical product development and, 2) to refine a list of 31 predefined patient group engagement activities. Results: Patient group and sponsor representatives described similar benefits: engagement activities can enhance the quality and efficiency of clinical trials by improving patient recruitment and retention, reduce costs, and help trials meet expectations of regulators and payers. All representatives indicated that investments include both dedicated staff time and expertise, and financial resources. Factors to consider when evaluating benefits and investments were also identified as were suggestions for clarifying the list of engagement activities. Discussion: Using these findings, we refined the 31 engagement activities to 24 unique activities across the medical product development lifecycle. We also developed a web-based prioritization tool (https://prioritizationtool.ctti-clinicaltrials.org/) to help clinical research sponsors and patient groups identify high priority engagement activities. Use of this tools can help sponsors and patient groups identify the engagement activities that they believe will provide the most benefit for the least investment and may lead to more meaningful and mutually beneficial partnerships in medical product development.
Thu, 2 July 2020
ARTICLE | doi:10.20944/preprints202005.0188.v2
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2 serology; ELISA; N protein; COVID-19; serosurvey
Online: 2 July 2020 (07:19:44 CEST)
As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.
Tue, 30 June 2020
ARTICLE | doi:10.20944/preprints202005.0368.v2
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV2; personal protection devices; snorkel masks; safety test
Online: 30 June 2020 (07:43:58 CEST)
Introduction: The SARS-CoV2 pandemic has led to an worldwide shortage of Personal Protection Devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO2) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A ‘fit’ test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO2 and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO2 was noted, remaining within physiological limits. Masks with specific adaptors (3D printed or provided by the manufacturer) are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts and choice of filter are important.
Sun, 28 June 2020
Online: 28 June 2020 (19:46:40 CEST)
Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.
SHORT NOTE | doi:10.20944/preprints202006.0325.v1
Subject: Medicine & Pharmacology, Other Keywords: GIS; health Infrastructure; National Portal; COVID-19; Hot-Spot mapping; Accessibility to services
Online: 28 June 2020 (09:00:04 CEST)
This short note proposes a national Geographic Information System (GIS) - based health infrastructure to deal with epidemics and pandemics. Currently, there is no pan-India health infrastructure available that can compile, update, and report the spread of epidemic diseases. It not only curtails the opportunity of finding the real-time data on the spatial distribution of a disease but prevents one to inquire into the causes of the disease through epidemiological analysis. The proposed infrastructure in this study is a pan-India one and can broadly be divided into two parts, hotspot mapping and accessibility to services. In the first part, hospitals are proposed to act as nodes of data collection, sending data to a national GIS portal. This portal shall have the capabilities of plotting the data using map rendering services such as Google and Bing Maps. This way, hotspots can be visualized in no time, benefitting the government and common citizenry alike. The second part deals with the accessibility of citizenry to a wide range of services, i.e., healthcare services, grocery outlets, emergency services, baby food, and many other essential services of the day to day life. In order to implement this, we propose that the government need to enforce a mandatory submission of locational coordinates of all Goods and Services Tax (GST) enrolled service providers. Once the coordinates are submitted, the government can effectively control the opening and closing of services and inform the citizenry at the same time. The proposed infrastructure is going to help deal with the extraordinary situations during epidemic and pandemics similar to what the world is currently facing in the form of Corona Virus Disease 2019 (COVID-19). Furthermore, the infrastructure can be scaled up or down as per the spread of a disease. The health-GIS platform proposed in this concept paper, shall help India in controlling and managing the epidemic more efficiently.
Sun, 21 June 2020
REVIEW | doi:10.20944/preprints202006.0278.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; serological diagnostic test; performance evaluation
Online: 21 June 2020 (14:58:20 CEST)
In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated COVID-19 disease has become a global pandemic causing significant mortality and morbidity. In the absence of vaccines and effective therapeutics, reliable serological testing can be a key element of public health policy to control further spread of the disease and gradually ease quarantine measures. However, prior to launch of large-scale seroprevalence studies to assess herd immunity, it is critical to understand the limits and potential of current SARS-CoV-2 serological tests on the market. In this study, we provide an overview of serological testing and conduct a systematic review of independent evaluations of SARS-CoV-2 serological tests performance. Our findings show significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid diagnostic tests with high performance level in detecting SRAS-CoV-2 specific antibodies. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests.
CASE REPORT | doi:10.20944/preprints202006.0269.v1
Online: 21 June 2020 (11:59:21 CEST)
Understanding the clinical conditions and outcomes of Covid-19 infected patients with immunodeficiency like HIV will be an information for improving management and treatment modalities. It was reported a patient of HIV plus clinical confirmed Covid-19 in this presentation.
CASE REPORT | doi:10.20944/preprints202006.0260.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19; pulse therapy; corticosteroids; immunoglobulin
Online: 21 June 2020 (11:06:08 CEST)
Three patients with severe life-threatening COVID-19 who failed to achieve substantial improvement on tocilizumab, received pulse therapy with corticosteroids (methylprednisolone, 1000 mg/day IV for three consecutive days) and intravenous immunoglobulin (20 g/day IV). This was associated with a prompt resolution of respiratory failure, elimination of cytokine release syndrome, and reversal of pulmonary CT changes. The treatment was generally safe and well tolerated. There was no evidence of protracted persistence of the virus in the patients who received pulse therapy. Randomized controlled trials are necessary to specify the efficacy and safety of high-dose methylprednisolone and intravenous immunoglobulin in the treatment of severe life-threatening COVID-19 separately or in combination.
ARTICLE | doi:10.20944/preprints202006.0246.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19 mortality rate; testing intensity; epidemiology; Europe; Asia; obesity; elderly
Online: 21 June 2020 (10:01:26 CEST)
Background: It is unclear why certain countries have been more severely affected by COVID-19 than other countries. Methods: In this ecological study we compared COVID-19 mortality and incidence/100,000 as well as 4 putative explanatory factors by WHO world region. Linear regression was then used to assess the country-level predictors of COVID-19 mortality/100,000 and incidence/100,000 in 204 countries with available data. Results: COVID-19 incidence and mortality/capita were greater in Europe than other regions. This was despite a higher testing rate in Europe than other regions. Europe had an older population than all other regions and a higher prevalence of obesity than Africa, South East Asia and the Eastern Mediterranean. Country level multiple linear regression revealed positive associations between mortality/capita and testing rate, percent of the population 65 years or older, and Europe compared to Western Pacific and South East Asia (all P<0.005). Results for the analyses with cases/100,000 as outcome variable were similar. Conclusion: Our results suggest that older populations as well as other undefined regional and national factors, possibly related to efficacy of control efforts, are responsible for differences in national severity COVID-19 epidemics.
Fri, 19 June 2020
ARTICLE | doi:10.20944/preprints202006.0237.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-CoV-2; risk factors; outcomes; cardiovascular; Latin America.
Online: 19 June 2020 (10:22:50 CEST)
Coronavirus disease 2019 (COVID-19) fatal outcomes have been associated with multiple cardiovascular risk factors. In new epidemic areas, such as Latin America, there is a lack of studies about this. Here, we evaluated those factors in a retrospective cohort of patients in a national reference hospital of Lima, Peru. Design. A retrospective cohort observational study was done. For this study, information was obtained from clinical records of the hospital for the cases that were laboratory-diagnosed and related, during March 6th and April 30th, 2020. rRT-PCR was used for the detection of the RNA of SARS-CoV-2 following the protocol Charité, Berlin, Germany, from nasopharyngeal swabs at the National Institute of Health. Calculation of the odds ratio (OR) with the respective 95% confidence interval (95% CI) was done, also logistic regression for adjusted OR (multivariate) was done. Values of p < 0.05 were considered significant for all analyses. Results. One hundred six hospitalized patients were evaluated. The mean age of patients was 61.58 years (SD 16.81). Cardiovascular risk factors among them were hypertension (46.2%), diabetes (28.3%), and obesity (28.3%), among others. Fifty-six patients died (52.8%). Mortality associated factors at the multivariate analysis were arterial hypertension (OR=1.343, 95% 1.089-1.667), myocardial injury (OR=1.303, 95% 1.031-1.642), and mechanical ventilation (OR 1.262, 95% 1.034-1.665), as associated factors. Conclusion. As observed in other regions of the world, cardiovascular risk factors represent a significant and independent threat to be considered in patients with COVID-19. Further studies and interventions in Peru and Latin America are expected.
Sun, 14 June 2020
ARTICLE | doi:10.20944/preprints202006.0188.v1
Subject: Medicine & Pharmacology, Other Keywords: sickle cell disease; knowledge assessment; practices; physicians; Democratic Republic of Congo
Online: 14 June 2020 (17:29:23 CEST)
Background: Sickle cell disease is a major public health issue in the DRC while it is still poorly understood by health professionals. The objective of this study was to assess the knowledge and practices of Congolese physicians treating sickle cell disease (SCD) in order to identify areas for improvement in clinical care. Methods: This is a descriptive observational study conducted on Congolese physicians using a questionnaire. Participants were evaluated on a pre-established answer grid. Results: A total of 460 physicians participated, including 81 women (18%) with an average age of 35 years (range 25–60 years). Most physicians were general practitioners. Although self-assessment of their level of knowledge on SCD was estimated as average to good, less than half of the participants (n= 460; 46%) reported adequate management of vaso-occlusive crisis but only 1% of them had received specific training on SCD. Most physicians reported difficulties both in terms of diagnostic (65%) and management (79%) options of SCD patients. This study showed also that 85% of them did not have access to diagnostic tools for SCD. Conclusions: Insufficient knowledge on SCD, poor diagnostic and treatment options may contribute to morbidity and mortality of patients living in the DRC. Interventions aiming at improving physician’s knowledge, patient’s follow-up and treatment access are needed. Specific training alongside existing programs (HIV, malaria), early diagnosis of the disease, and creation of patients’ advocacy groups should improve SCD patient’s care.
REVIEW | doi:10.20944/preprints202006.0174.v1
Subject: Medicine & Pharmacology, Other Keywords: Acinetobacter baumannii; colistin; tigecycline; resistance; in vivo
Online: 14 June 2020 (14:16:40 CEST)
The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.
REVIEW | doi:10.20944/preprints202006.0173.v1
Subject: Medicine & Pharmacology, Other Keywords: pandrug-resistant; treatment; carbapanemase; Acinetobacter; Klebsiella; Pseudomonas
Online: 14 June 2020 (13:19:32 CEST)
The management of carbapenem-resistant infections is often based on colistin, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, colistin and tigecycline (CACT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CACT-resistant GNB are scarce and based exclusively on few case reports and small case series but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review we consolidate the available literature to inform clinicians dealing with CACT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CACT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Several treatment options are currently available for CACT-resistant K. pneumonia. Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g. colistin- or fosfomycin-based synergistic combinations) may represent a last resort option but their use against CACT-resistant GNB requires further study.
COMMUNICATION | doi:10.20944/preprints202006.0171.v1
Online: 14 June 2020 (12:57:23 CEST)
The COVID-19 pandemic changed the world of medical education, moving it years ahead of time into the future. Many concepts needed to be changed, so did the methodologies. Nevertheless, clinical assessment remained tricky. This work highlights the outcome of the work of College of Medicine and Medical Sciences at the Arabian Gulf University in Bahrain in performing virtual clinical examination using Zoom™. Tips in this article are meant to help plan, implement and evaluate clinical assessments virtually.
ARTICLE | doi:10.20944/preprints202006.0161.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Coronavirus; Artificial intelligence; Machine learning; Data mining
Online: 14 June 2020 (03:34:22 CEST)
The novel coronavirus disease (COVID-19) pandemic has impacted health and wellbeing globally. To strengthen preventive and clinical care amid this pandemic, technological innovations like artificial intelligence (AI) are increasingly used in different contexts. This bibliometric study aimed to assess the current scholarly development and prominent research domains in applications of AI technologies in COVID-19 research. A total of 105 articles were retrieved from MEDLINE database that emphasized on the use of AI in the context of COVID-19. Most articles had multiple authors with a collaboration index of 7.18. Moreover, most of the articles were produced from the USA (22.86%) and China (21.9%), whereas developing countries were underrepresented among the contributing nations. Furthermore, several research domains were identified, including prevention and control, diagnostics, epidemiological characteristics, therapeutics, psychological conditions, and different areas of data sciences related to COVID-19. The current bibliometric evidence shows the early stage of development in this field, which necessitates equitable applications of AI in COVID-19 research emphasizing on health disparities, socio-legal issues, vaccine development, and applied public health research in this pandemic.
Fri, 12 June 2020
ARTICLE | doi:10.20944/preprints202006.0153.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19; geographical information systems (GIS); coronavirus; epidemiology of infectious diseases; public health.
Online: 12 June 2020 (12:36:52 CEST)
The epidemic of Coronavirus Disease 2019 (COVID-19) have affected all the regions of the world, nevertheless, in some countries there is a lack of studies on its main clinical and epidemiological features. We analyzed the incidence, incidence rates, and evolution of COVID-19 cases in Honduras from February 18-April 24, 2020.Methods: Using daily epidemiological data from surveillance about COVID-19 in Honduras, we calculated the rates of incidence (cases/100,000 population), and developed at national, departmental, and municipal levels GIS-based maps.Results: February 18 - April 24, 2020, a sum of 3,169 suspected COVID-19 cases have been assessed by RT-PCR, 533 (16.8%) of them were positive, for an incidence rate of 5.73 cases/100,000 pop. The highest peak was reached on March 31 (48 cases). The department with the highest number of cases and incidence rate was Cortes (383 cases, 71.9% of the total, 21.45 cases/100,000 pop). Discussion: The pattern and evolution of COVID-19 epidemic in Honduras has been particularly focused in the major urban areas, San Pedro Sula and Tegucigalpa, the capital city. Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of the evolution of the pandemic and monitoring interventions.
Tue, 9 June 2020
CASE REPORT | doi:10.20944/preprints202006.0113.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-CoV-2; ARDS; bronchoalveolar lavage fluid (BALF)
Online: 9 June 2020 (03:30:05 CEST)
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affects the respiratory system with some patients rapidly progressing to acute respiratory distress syndrome (ARDS). The most common symptoms of the patients are fever, cough, dyspnea, myalgia, and fatigue. Nasopharyngeal and oropharyngeal swab specimens tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) are the most commonly used methods to diagnose COVID-19. Herein, we investigate and discuss a young case of COVID-19, without any pre-existing medical conditions, whose both nasopharyngeal and oropharyngeal swab tests of SARS-CoV-2 were negative in the prodromal phase. However, after three days, with severe dyspnea and rapidly progressed acute respiratory distress syndrome (ARDS), the case was identified as infected by COVID-19 by testing bronchoalveolar lavage fluid (BALF). The patient was intubated in the intensive care unit (ICU) but expired on the fourth day. This case shows the importance of active and accurate monitoring of the patients showing COVID-19 symptoms. Although the BALF test has a higher exposure risk, it is considered more accurate and recommended if performed by an expert operator.
Sun, 7 June 2020
REVIEW | doi:10.20944/preprints202006.0109.v1
Subject: Medicine & Pharmacology, Other Keywords: surgery; surgical practice; COVID-19; pandemic; SARS-CoV-2; review; consensus; guidelines
Online: 7 June 2020 (16:38:30 CEST)
The coronavirus disease-2019 (COVID-19) pandemic is an ongoing pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Although COVID-19 pandemic is not a direct surgical problem, its impact on the surgical units has been substantial. Many operations have been cancelled or deferred due to risk of disease spread and staff shortages. Operating theatres are identified as areas of high risk of disease transmission due to aerosol generation during the surgical procedures and prolonged patient contact. Resource limitations, including lack of personal protective equipment (PPE) and limited availability of testing, continue to expose the surgical community to COVID-19. In this review, evidence and consensus guidelines on surgical practice during the COVID-19 pandemic are summarised and described. Immediate action is deemed essential to ensure unhindered provision of surgical care while optimizing the use of limited resources and ensuring staff safety.
Fri, 5 June 2020
REVIEW | doi:10.20944/preprints202006.0045.v1
Subject: Medicine & Pharmacology, Other Keywords: ARDS; COVID-19; Berlin Criteria; Respiratory Failure
Online: 5 June 2020 (13:54:36 CEST)
Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.
Wed, 3 June 2020
ARTICLE | doi:10.20944/preprints202006.0012.v1
Subject: Medicine & Pharmacology, Other Keywords: psoriasis; osteoporosis; cohort studies; Case-Control Studies; risk factors
Online: 3 June 2020 (05:50:13 CEST)
Objectives: The aim of the present study was to evaluate the association between psoriasis and osteoporosis using two different studies. Methods: Data from the Korean National Health Insurance Service-Health Screening Cohort of participants who were ≥ 40 years old were collected from 2002 to 2013. Psoriasis and osteoporosis were included using ICD-10 codes. In study I (a follow-up study), a total of 25,306 psoriasis participants were matched to 101,224 controls with respect to age group, sex, income group, and region of residence, and the occurrence of osteoporosis was analyzed. Crude (simple) and adjusted hazard ratios (HRs) were analyzed using a stratified Cox proportional hazard model. In study II (a nested case–control study), a total of 79,212 osteoporosis patients were matched to 79,212 controls, and a previous history of psoriasis was analyzed. Crude and adjusted odds ratios (ORs) were analyzed using a conditional logistic regression analysis. Subgroup analyses were conducted according to age group and sex. Results: The adjusted HR of osteoporosis was 1.11 (95% confidence interval [CI] = 1.07-1.15, P < 0.001) in study I. In the subgroup analysis according to age and sex, the results were consistent except for the ≥ 60-year-old women. The adjusted OR of psoriasis was 1.22 (95% CI = 1.16-1.28, P < 0.001) in study II. All subgroups demonstrated high adjusted ORs of osteoporosis for psoriasis. Conclusions: Psoriasis increased the risk of osteoporosis in the population of participants aged ≥ 40 years in Korea.
ARTICLE | doi:10.20944/preprints202004.0308.v5
Subject: Medicine & Pharmacology, Other Keywords: Covid-19; SARS-Cov-2; Mortality rate; Cancer; Cardiovascular disease; Respiratory disease; Diabetes; Kidney diseases; April; May
Online: 3 June 2020 (05:49:12 CEST)
Covid-19 has given a halt to all the activities in the world. Europe was most affected, followed by the United States of America. It has taken more than 350000 lives until now. In this study, we have assessed the severity of Covid-19 by analyzing the mortality rate of Covid-19 and other chronic diseases. The Covid-19 data and “death rate” data caused by other diseases were downloaded from the world health organization (WHO) website. A normalized method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths caused by Covid-19 in April 2020 have overtaken the average number of deaths caused by Cancer, Cardiovascular diseases, and other diseases in Belgium, the United Kingdom (UK), Spain, France, and Ireland. Covid-19 was found to be strongly correlated with non-communicable respiratory diseases and Cancer with correlation coefficients 0.73 and 0.67 respectively. The severity of Covid-19 in the United States of America (USA) was moderate. The severity of Covid-19 in Asian countries was found to be low. Europe showed the highest diversity in the mortality rate of Covid-19. On average, except for a few European countries, Cardiovascular diseases, cancer, and non-communicable respiratory diseases were still more lethal and caused more deaths than Covid-19.
Tue, 2 June 2020
REVIEW | doi:10.20944/preprints202006.0002.v1
Subject: Medicine & Pharmacology, Other Keywords: Biostatistics; Data management; Reproducibility; Workflow automation
Online: 2 June 2020 (09:24:25 CEST)
The complexity of analysis pipelines in biomedical sciences poses a severe challenge for the transparency and reproducibility of results. Researchers are increasingly incorporating software development technologies and methods into their analyses, but this is a quickly evolving landscape and teams may lack the capabilities to set up their own complex IT infrastructure to aid reproducibility. Basing a reproducible research strategy on readily available solutions with zero or low set-up costs whilst maintaining technological flexibility to incorporate domain-specific software tools is therefore of key importance. We outline a practical approach for robust reproducibility of analysis results. In our examples, we rely exclusively on established open-source tools and free services. Special emphasis is put on the integration of these tools with best practices from software development and free online services for the biostatistics domain.
Sun, 31 May 2020
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-CoV2; Public AwareneSs; Public Practice; Social Distancing and Saudi Arabia
Online: 31 May 2020 (21:27:01 CEST)
Objectives: Social distancing measures are currently implemented to control COVID-19 pandemic in many countries, including Saudi Arabia. The aim of this study was therefore to evaluate the awareness and adherence of the Saudi population to these measures. Methods: A web-based questionnaire was designed with 16 questions (8 questions related to demographics, 3 in relation to awareness about social distancing and 5 related to overall practice of social distancing). Results: 5105 participants completed the survey [58.4% female, 66.3% young individuals (aged 18-37 years), 55.8% bachelor degree holders, and 51.0% from the western region]. The Saudi Ministry of Health (MOH) was the main source of information about COVID-19 for most participants (78.2%). High awareness (81.3%) regarding social distancing was observed, associated mainly with female participants, those from the middle region and those with high education and income. Overall implementation of social distancing was satisfactory (score 3.13/5), with 37.8% never leaving home during the home-stay period. Better adherence to social distancing was observed for female participants, higher degree holders and those aged over 38 years. Conclusions: Organised plans by the Saudi MOH have been effective in raising awareness and improving practice of social distancing among public. However, the observed lower practice of social distancing by individuals with lower education and income indicates the need for targeted interventions to achieve better outcome.
CASE REPORT | doi:10.20944/preprints202005.0509.v1
Online: 31 May 2020 (20:50:18 CEST)
“Severe acute respiratory syndrome” (SARS) due to Coronavirus (SARS-CoV) infection is a known cause of death. Sometimes demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flue-like symptoms. In this dobtfull cases the forensic pathologist could be requested to define cause of death occurred outside hospital. In this report the authors describe two thorough autopsied cases of SARS-CoV-2 related deaths occurred suddenly at home and not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.
REVIEW | doi:10.20944/preprints202005.0470.v1
Subject: Medicine & Pharmacology, Other Keywords: coronavirus; COVID-19; facial protection; masks; PAPR
Online: 31 May 2020 (15:02:43 CEST)
We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin-health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.
Tue, 26 May 2020
ARTICLE | doi:10.20944/preprints202005.0431.v1
Subject: Medicine & Pharmacology, Other Keywords: Hip fracture; Casemix; Validation; Discrimination; Risk score; Calibration
Online: 26 May 2020 (11:40:33 CEST)
Objectives: Independent validation of risk scores after hip fracture is uncommon, particularly for evaluation of outcomes other than death. We aimed to assess the Nottingham Hip Fracture Score (NHFS) for prediction of mortality, physical function, length of stay and postoperative complications. Design: Analysis of routinely collected prospective data. Setting and Participants: Consecutive hip fracture patients were identified from the Northumbria hip fracture database between 2014-2018. Patients were excluded if they were not surgically managed or if scores for predictive variables were missing. Methods: C-statistics were calculated to test the discriminant ability of the NHFS, Abbreviated Mental Test Score (AMTS), and ASA grade for in-hospital, 30- and 120-day mortality, functional independence at discharge, 30-days and 120-days, length of stay, and postoperative complications. Results We analysed data from 3208 individuals, mean age 82.6 (SD 8.6). 2192 (70.9%) were female. 194 (6.3%) died during the first 30-days, 1686 (54.5%) were discharged to their own home, 211 (6.8%) had no functional mobility at 120-days, 141 (4.6%) experienced a postoperative complication. The median length of stay was 18 days (IQR 8-28). For mortality, c-statistics for the NHFS ranged from 0.68-0.69, similar to ASA and AMTS. For functional independence, the c-statistics for the NHFS ranged from 0.74-0.83, similar to AMTS (0.61-0.82) and better than the ASA grade (0.68-0.71). Length of stay was significantly correlated with each score (p<0.001 by Jonckheere-Terpstra test); NHFS and AMTS showed inverted U-shaped relationships with length of stay. The best predictor of postoperative complications was ASA grade (0.56-0.64), whilst NHFS (0.49-0.59) and AMTS (0.48-0.57) performed similarly poorly. Conclusions and Implications: The NHFS performed consistently well in predicting functional outcomes, moderately in predicting mortality, but less well in predicting length of stay and complications. There remains room for improvement by adding further predictors such as measures of physical performance in future analyses.
Subject: Medicine & Pharmacology, Other Keywords: SARS‐CoV‐2; CoVID-19; healthcare workers; HCWs protection; Lodi; infection prevention and control strategies
Online: 26 May 2020 (08:25:05 CEST)
The report describes organizational and occupational strategies adopted by Lody Public Hospital (the first epicentre of Covid-19 outbreak in Italy) in order to face pandemic. Occupational Safety System (OSH) introduced infection prevention and control strategies (IPC) for the protection of healthcare workers (HCWs, while a reorganization of whole hospital based on the level of intensity of care for COVID-19 patients was estabilished. Screening on HCWs (N= 248) by nasopharyngeal swabs for SARS-CoV-2 and comparison between HCWs and local population (N=1123) are shown. These preliminary data, collected from 25th February till 25th March 2020, confirms that measures adopted mitigate the effects of virus transmission within the hospital and reduced the HCW component of the transmission of the infection. Additional studies in depth are currently underway.
Mon, 25 May 2020
REVIEW | doi:10.20944/preprints202005.0411.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Clinical Trials; disruption; non-COVID-19 clinical trials; drugs; therapeutic area
Online: 25 May 2020 (11:17:56 CEST)
COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.
Sun, 24 May 2020
COMMUNICATION | doi:10.20944/preprints202005.0395.v1
Online: 24 May 2020 (18:19:02 CEST)
We present a modification of the logistic model of epidemics that takes into account the possibility that an epidemic can develop from multiple physically-distinct hot spots with a range of starting times. This produces an improved understanding of the time evolution of the COVID-19 epidemic taking place in the United States in the spring of 2020.
REVIEW | doi:10.20944/preprints202005.0385.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Thrombosis; Inflammation; ADAMTS13; Von Willebrand Factor
Online: 24 May 2020 (16:17:00 CEST)
Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Following its origin as a regional outbreak in Wuhan, China, COVID-19 rapidly spread globally and eventually was designated as pandemic by the World Health Organization. Multiple studies describing the clinical characteristics of COVID-19 patients highlighted the prevalence of abnormal coagulopathy and higher incidence of thrombosis. These studies identified co-morbid inflammatory disorders as risk factors for hospitalization in SARS-CoV-2 infections. While early evidence suggested inflammatory conditions as the leading cause of abnormal coagulopathy in COVID-19 patients, the mechanisms behind progression of inflammation mediated hemostasis dysregulation to thrombotic outcomes in susceptible individuals are not well understood. In addition, a sensitive and temporal assessments of coagulation and fibrinolysis is still lacking. Von Willebrand Factor (VWF) and ADAMTS13 interactions play an important role in the maintenance of hemostasis and prevention of unwanted thrombosis. In inflammatory conditions, VWF-ADAMTS13 imbalance characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS13 is reported. Also, an imbalance between ADAMTS13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. Despite the natural antithrombotic activity of ADAMTS13, its role in COVID-19 pathophysiology, specifically thrombotic outcomes has not yet been investigated. A thorough understanding of VWF-ADAMTS13 interactions during early and advanced phases of COVID-19 could help define the pathophysiology, guide thromboprophylaxis and treatment and improve clinical prognosis.
Sat, 23 May 2020
ARTICLE | doi:10.20944/preprints202005.0368.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV2; personal protection devices; snorkel masks; safety test
Online: 23 May 2020 (10:18:39 CEST)
Introduction: The SARS-CoV2 pandemic has led to an worldwide shortage of Personal Protection Devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO2) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A “fit” test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO2 and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO2 was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts and choice of filter are important.
BRIEF REPORT | doi:10.20944/preprints202005.0361.v1
Online: 23 May 2020 (05:40:26 CEST)
Italy suffered heavily with the new pandemic crisis caused by the novel coronavirus SARS-CoV-2. Given the low number of tests performed on the early stages of the outbreak, Italy lost track of most of infections. We use a modified SEIR model to reconstruct the most realistic infection curve using the hospitalization curve of the registered data. Using this method we estimated that, by the end of the first infection wave, about 3-4% of the population will have been infected by the virus. Following the same process, the number of deaths is projected to be between 100000 to 115000. We also find a significant correlation between the number of tests performed, the fraction of undocumented infections and the rate of change dI/dt of the real infection curve. We conclude that herd immunity is not enough to contain further spread of the disease inside the country.
Thu, 21 May 2020
ARTICLE | doi:10.20944/preprints202005.0338.v1
Subject: Medicine & Pharmacology, Other Keywords: pharmacy practice; infection control; sanitation; COVID-19; SARS-CoV-2; pharmacists; public health; workplace safety
Online: 21 May 2020 (08:37:52 CEST)
Background: Australia received its first case of coronavirus on 25 January 2020. Since then the demands of COVID-19 has presented unparalleled levels of strain on the public healthcare systems in the country. In this time of crisis, pharmacists and community pharmacy staff have modified work strategies according to the rapidly changing environment. With a delayed dissemination of resources and guidelines, pharmacist and pharmacies are practicing innovative infection control methods across Australia to protect their staff, patients and the community. This article seeks to explore the current activities undertaken by pharmacists in various community pharmacy settings across Australia in relation to the safety of the workplace environments for staff and patients. Information collected can help inform future decisions in pandemic preparation for pharmacies in response to similar health crisis now and in the future. Methods: An online cross-sectional survey study was conducted in Australia during the COVID-19 outbreak from 1st to 30th April 2020. The questionnaire addressed community pharmacist’s awareness and response to infection and sanitation control. Results: A total of 137 pharmacists took part in the survey, with almost half (45.26%) belonging to the age group of 25 to 34 years. Community pharmacy formed the bulk (89.05%) of the respondent’s primary place of practice. There was a good uptake of safety measures by pharmacists and their pharmacies to protect staff and patients. However the task of reassigning high health risk staff was not heavily practiced (34.31%). Regular cleaning took place in the pharmacy, but the use of gloves while cleaning was not practiced in 48.18% of respondents. In addition, only 46.72% of respondents reported observing script baskets being cleaned and disinfected. About one-third (37.96%) of pharmacists were aware of the two-step cleaning and disinfecting process, but only 18.98% of pharmacists reported observing or performing this sanitation procedure. More than half of surveyed pharmacists reported having difficulty keeping up with infection control changes and pharmacy practice guidelines during the pandemic. Conclusion: This study demonstrates that the majority of pharmacists are not fully aware of the infection control measures needed in a community pharmacy setting. The influx of coronavirus updates has made it difficult for pharmacists to implement accurate procedures on some aspects of workplace hygiene, which may have led to some gaps in infection control measures. Pharmacists must aim to uphold their public health ambassador role and aim to keep up-to-date with professional guidance to provide the necessary infection control measures to ensure staff, patient and public health safety.
Wed, 20 May 2020
BRIEF REPORT | doi:10.20944/preprints202005.0327.v1
Subject: Medicine & Pharmacology, Other Keywords: anosmia; ageusia; clinical manifestations; neurological; SARS-CoV-2; COVID-19
Online: 20 May 2020 (10:39:41 CEST)
Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR confirmed SARS-CoV-2 infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.
REVIEW | doi:10.20944/preprints202004.0470.v2
Subject: Medicine & Pharmacology, Other Keywords: non-pharmacological interventions; COVID 19; health policy; mortality; economic; intensive care unit
Online: 20 May 2020 (04:38:52 CEST)
Non-pharmacological interventions in the fight against COVID 19 include: a) suppression, which facilitates its extinction; and b) mitigation, which reduces its speed of spread. Left unmitigated, the intensive care unit bed capacity (ICU) is exceeded over its maximum supply, resulting in increased deaths. Suppression has shown in simulation models the potential for decreasing ICU occupation below its surge limit, effectively decreasing mortality. However, for avoiding a rebound in transmission, suppression must be maintained intermittently until a vaccine is available (which may take up to 2 years). The objective of this paper was to describe the mortality patterns observed in Spain, Italy and South Korea for discussing a hypothetical combined public health policy and socioeconomic model that could potentially reduce mortality while reducing the economic impact of this pandemic in Spain. The plan is based on a progressive-voluntary reinstatement to work of the population exposed to the lowest risks (healthy non-immune family units <50 y/o and immune population) and it depends on having sufficiently available ICU beds for providing adequate support. This model, if proven correct for Spain, could eventually be followed by other countries facing a similar impact of the present pandemic.
Tue, 19 May 2020
REVIEW | doi:10.20944/preprints202005.0314.v1
Subject: Medicine & Pharmacology, Other Keywords: antiretroviral therapy; differentiated service delivery; retention; suppression; Africa; systematic review
Online: 19 May 2020 (09:53:46 CEST)
Introduction: Differentiated service delivery (DSD) models for antiretroviral treatment (ART) for HIV are being scaled up in the expectation that they will improve the quality and efficiency of treatment delivery and reduce costs while maintaining at least equivalent clinical outcomes. Even this minimum requirement of equivalent clinical outcomes is poorly documented for most models and settings, however. We reviewed the recent literature on DSD models to describe what is known about clinical outcomes. Methods: We conducted a rapid systematic review of peer-reviewed publications in PubMed, Embase, and the Web of Science and major international conference abstracts that reported outcomes of DSD models for the provision of ART in sub-Saharan Africa from January 1, 2016 to September 12, 2019. Sources reporting standard clinical HIV treatment metrics, primarily retention in care and viral load suppression, were reviewed and categorized by DSD model and source quality assessed. Results and Discussion: Twenty-nine papers and abstracts describing 37 DSD models and reporting 52 discrete outcomes met search inclusion criteria. Of the 37 models, 7 (19%) were facility-based individual models, 12 (32%) out-of-facility based individual models, 5 (14%) client-led groups, and 13 (35%) healthcare worker-led groups. Retention was reported for 73% of the models and viral suppression for 57%. Where a comparison with conventional care was provided, retention in most DSD models was within 5% of that for conventional care; where no comparison was provided, retention generally exceeded 80%. For viral suppression, all those with a comparison to conventional care reported a small increase in suppression in the DSD model; reported suppression exceeded 90% in 11/21 models. Analysis was limited by the extensive heterogeneity of study designs, outcomes, models, and populations. Most sources did not provide comparisons with conventional care, and metrics for assessing outcomes varied widely and were in many cases poorly defined. Conclusion: Existing evidence on the clinical outcomes of DSD models for HIV treatment in sub-Saharan Africa is limited in both quantity and quality but suggests that retention in care and viral suppression are roughly equivalent to those in conventional models of care.
REVIEW | doi:10.20944/preprints202003.0103.v2
Subject: Medicine & Pharmacology, Other Keywords: Coronavirus; SARS-CoV; MERS-CoV; serology; molecular diagnosis; reservoir; public health
Online: 19 May 2020 (04:13:19 CEST)
Introduction: Coronaviruses are zoonotic viruses that include human epidemic pathogens such as the Middle East Respiratory Syndrome virus (MERS-CoV), and the Severe Acute Respiratory Syndrome virus (SARS-CoV), among others (e.g., COVID-19, the recently emerging coronavirus disease). The role of animals as potential reservoirs for such pathogens remains an unanswered question. No systematic reviews have been published on this topic to date. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess MERS-CoV and SARS-CoV infection in animals and its diagnosis by serological and molecular tests. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 6,493articles were retrieved (1960-2019). After screening by abstract/title, 50 articles were selected for full-text assessment. Of them, 42 were finally included for qualitative and quantitative analyses. From a total of 34 studies (n=20,896 animals), the pool prevalence by RT-PCR for MERS-CoV was 7.2% (95%CI 5.6-8.7%), with 97.3% occurring in camels, in which pool prevalence was 10.3% (95%CI 8.3-12.3). Qatar was the country with the highest MERS-CoV RT-PCR pool prevalence, 32.6% (95%CI 4.8-60.4%). From 5 studies and 2,618 animals, for SARS-CoV, the RT-PCR pool prevalence was 2.3% (95%CI 1.3-3.3). Of those, 38.35% were reported on bats, in which the pool prevalence was 14.1% (95%CI0.0-44.6%). Discussion: A considerable proportion of infected animals tested positive, particularly by nucleic acid amplification tests (NAAT). This essential condition highlights the relevance of individual animals as reservoirs of MERS-CoV and SARS-CoV. In this meta-analysis, camels and bats were found to be positive by RT-PCR in over 10% of the cases for both; thus, suggesting their relevance in the maintenance of wild zoonotic transmission.
Mon, 18 May 2020
ARTICLE | doi:10.20944/preprints202005.0306.v1
Subject: Medicine & Pharmacology, Other Keywords: acute kidney injury; HPB surgery; perioperative care; critical care
Online: 18 May 2020 (17:29:02 CEST)