cord-000843-e1bn79ui	2011	The role of radiology includes (a) characterisation of sonographically indeterminate adnexal masses, (b) staging as guidance for surgery and treatment planning (including identification of sites of non optimal resectabilty) in suspected ovarian cancer, (c) assessment of recurrent disease, and (d) in selected cases image-guided biopsy. The association of multiple markers of structural and functional imaging (MRI and PET) and the use of advanced computational analysis techniques will allow better management of AD but it needs a broader validation and know the most efficient combination of biomarkers at each stage of the disease, including the preclinical period. Although the basic techniques for DCE-CT have been available for decades, more recently a range of technological advances have contributed to the greater applicability of perfusion CT in the clinical environment including wider CT detectors, shorter gantry rotation times, ''table-toggling'', radiation dose reduction and software corrections for image mis-registration due to respiratory or other patient motion.
cord-001221-due9tloa	2014	In short: obtaining samples for making an accurate diagnosis and also to know more about its specific biology (biomarkers); IR covers any possibility needed for vascular access; percutaneous needle ablation is the best alternative in selected patients; endovascular embolisation with "vehiculisation" of therapies is an outstanding method for selective treatment, and sometimes precise ablation, of different tumors; IR is a unique way to offer palliation in a wide range of tumoral complications, such as embolisation for bleeding, stenting for vein obstructions or drainage of fluid collections. CT may be useful for osteoid osteoma and MRI is the best imaging technique for further diagnosis and staging by displaying tumour composition and extent of bone marrow involvement, including skip lesions, presence and extent of extraosseous soft tissue mass, and involvement of neurovascular bundle, muscle compartments and adjacent joint.
cord-001687-paax8pqh	2013	Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. Engineering functional bone using combinations of cells, scaffolds and bioactive factors are seen as a promising approach and these techniques will undoubtedly lead to ceaseless possibilities for tissue regeneration and repair. According to the "diamond concept" of bone tissue engineering (77) (78) , an ideal bone substitute material should offer an osteoinductive three-dimensional structure, contain osteogenic cells and osteoinductive factors, have sufficient mechanical properties and promote vascularisation. As reviewed in detail in Reference (200) , we were able to demonstrate the in vivo capability of our composite scaffolds in combination with growth factors or cells to promote bone regeneration within ectopic sites or critical sized cranial defects in the small animal models.
cord-002626-jzwwses4	2017	Clinical laboratories have thus had to develop new assays or modified the existing FDA-approved ones to detect high-risk HPV genotypes in head and neck cancer specimens. The vast majority of reporting laboratories utilized LDPs. 57 KRAS and RAS family gene mutation analysis is also critical in the management of patients with non-small-cell lung cancer (NSCLC) and other tumors, 58 for which FDA approval of kits has not occurred; LDPs or off-label use of kits is required. 74, 75 The FDA approval of anti-EGFR therapies based on clinical trial outcomes data resulted in the need for clinical laboratories to test tumor tissue for the EGFR-sensitizing mutations in order for patients to be eligible for treatment. During those ground-breaking first 15 years of the targeted cancer therapy era, if the laboratory community had been prohibited from providing high-quality, standardized LDP-based testing under existing CLIA guidelines, the negative consequences to patient care in the past and the future would have been substantial.
cord-003316-r5te5xob	2018	WGS-based strain identification gives a far superior resolution In principle, WGS can provide highly relevant information for clinical microbiology in near-real-time, from phenotype testing to tracking outbreaks. As an example, genome assembly might appear to be a bottleneck for real-time WGS diagnostics, but is probably rarely required; sufficient characterization of an isolate can be made by analysis of the k-mers in the raw sequence data, which is orders of magnitude faster. These include, among others: the current costs of WGS, which remain far from negligible despite a common belief that sequencing costs have plummeted; a lack of training in, and possible cultural resistance to, bioinformatics among clinical microbiologists; a lack of the necessary computational infrastructure in most hospitals; the inadequacy of existing reference microbial genomics databases necessary for reliable AMR and virulence profiling; and the difficulty of setting up effective, standardized, and accredited bioinformatics protocols.
cord-003878-nmyyt51x	2012	The discovery of these discrepancies in the autopsy room is a powerful tool for identifying faults in medical practice and shows the need for clinical audits. Their reasons vary from distaste for the procedure to a belief that the accuracy of modern investigative techniques avoids the need of autopsy in elucidating nothing extra to the clinical picture. Their increasing clinical confidence in the ante-mortem diagnoses supplants their need to request autopsies. Paradoxically, community doctors generally show that they appreciate receiving autopsy reports and that, in a high proportion of cases, the findings are unexpected and could influence their future clinical practice. If clinical autopsy rates continue to decline, the future practice of medicine will be blind to many adverse consequences of clinical actions and omissions. We advocate close communication between pathologists and clinicians in the context of the results of autopsy findings. Post-mortem imaging as an alternative to autopsy in the diagnosis of adult deaths: validation study Death of the teaching autopsy
cord-007321-7gi6xrci	1992	These guidelines for the evaluation of drugs for the treatment of respiratory tract infections include acute streptococcal pharyngitis and tonsillitis, acute otitis media, acute and chronic sinusitis, acute exacerbations of chronic bronchitis, and acute infectious pneumonia (table 1). This is often the case in otitis media, sinusitis, and pneumonia, when the use of invasive procedures such as tympanocentesis, sinus puncture, or transtracheal aspiration to confirm microbial eradication in the patient who is improving clinically generally is considered unjustified. Patients eligible for study entrance are children or adults with symptomatic pharyngitis or tonsillitis of acute onset clinically consistent with infection with group A I3-hemolytic streptococci and from whom group A (3-hemolytic streptococci have been isolated in cultures of throat -swab specimen or for whom a rapid screening test has indicated the presence of streptococci.
cord-007331-wccmeaep	2017	Differential diagnoses for the ferret in respiratory distress include pleural effusion (cardiac disease, neoplasia, infection, heartworm disease, hypoproteinemia, metabolic disease); pulmonary edema (cardiac disease, hypoproteinemia, metabolic disease, electrical cord bite); anterior mediastinal mass; pneumonia; pneumothorax; diaphragmatic hernia; tracheal obstruction; metabolic disease (acidosis); and profound weakness (circulatory collapse, hypoglycemia, anemia).21,36 Hyperthermia or pain may also manifest as dyspnea in ferrets. In contrast to the canine patient, diarrhea in the ferret is difficult to classify as being small intestinal or large intestinal in character.26 Differential diagnoses for diarrhea include GI foreign body or trichobezoar, dietary indiscretion, Helicobacter mustelae gastritis, eosinophilic gastroenteritis or other inflammatory bowel disease, neoplasia, metabolic disease (i.e., hepatopathy), clostridial overgrowth subsequent to prolonged antibiotic administration, influenza, rotavirus (usually in very young, unweaned ferrets), eDV (generally accompanied by respiratory signs and a crusting dermatitis), epizootic catarrhal enteritis ("green slime disease"), GI parasitism (i.e., coccidiosis, giardiasis), and proliferative bowel disease.
cord-009664-kb9fnbgy	2014	Because of the conflicting reports and lack of published data from paediatric patients, we sought to assess possible MIC change over time and to compare results generated by using different methodologies including Etest, agar dilution, and broth microdilution (MicroScan) methods. Recently, in vitro and in vivo studies have shown that NO plays a key role in the eradication of the leishmania parasite Objective: To determine whether a NO donor patch (developed by electrospinning technique) is as effective as meglumine antimoniate in the treatment of CL while causing less adverse events Methods: A double-blind, randomised, placebo-controlled clinical trial was conducted with 178 patients diagnosed with CL in Santander, Colombia, South-America. To follow the development and spread of the resistance among these strains is difficult, as antibiotic susceptibility testing of clinically relevant anaerobes in different routine laboratories in Europe is less and less frequently carried out due to the fact, that clinicians treat many presumed anaerobic infections empirically.
cord-010980-sizuef1v	2020	We hypothesized that presentation to a PTC would yield increased mortality when subspecialty intervention was required and that this would be most pronounced at night when in-house attending coverage is absent at all state PTCs. Materials and methods: A review of the Pennsylvania Trauma Outcome Study (PTOS) database was performed to capture patients aged 12-18 who underwent any non-orthopedic trauma surgery. Traumatic subaxial cervical fractures: functional prognostic factors and survival analysis Introduction: The main goal of this study is to identify the risk factors for poor functional outcomes and to analyze the overall survival (OS) and complications rate in patients with traumatic cervical spinal cord injury (SCI) and subaxial cervical fracture (SACF) treated with open surgical fixation. After applying a multiple imputation on all the study variables, a logistic regression generalized estimating equation after adjustment for age, sex, mechanism of trauma, and the injury severity score as covariates and hospitals as a cluster assessed an association between quartile of patient volume in intensive care unit and hospital mortality.
cord-011282-hgzneooy	2019	Following the resolution adopted at the first International Clinical Engineering and Health Technology Management Congress [8] that took place in Hangzhou, China, in October 2015, senior members from the CE profession from around the world who participated in the Global CE Summit [9] initiated the international project seeking evidence to the hypothesis that the engagement of CE and BE in guiding HT deployment positively impacts patient outcomes while the null hypothesis was that there is no difference. Safety and Quality services that dependent on complex technological systems is critical for outcomes and therefore identified with its own group of data Technology management group was the next category to be reviewed where CE/BME contributions to organized, integrate, manage, and improve safe and efficient sustainable HT. Overall this review identified evidence from 400 case studies received from 125 countries where management of medical devices (as main component of health technologies) made a positive difference over the past twelve years.
cord-014337-nnuvrb6o	2020	gdc-uk.org/news-blogs/news/detail/2020/09/01/ joint-statement-on-arrangements-for-dental-educationand-training-while-measures-are-in-place-to-control-thespread-of-covid-19-(version-2-dated-1-september-2020) (accessed November 2020). To evaluate the existing curricula and reorganise them by adopting the Commission on Dental Accreditation (CODA) compliance protocols on the interruption of education and distance education to allow for a continuation of the PGRs'' hands-on and didactic learning 2. Clinical case presentations through online sessions allowed continued PGRs'' feedback to enhance their presentation and treatment planning skills as well as surgical techniques 3. 1 report that sequencing data indicate high reads for Prevotella, Staphylococcus and Fusobacterium in patients severely infected with SARS-CoV-2. Despite facing changes in a teaching format, especially in clinical training, our approaches, including the use of online portals and modules, maintained and enhanced PGRs'' hands-on and didactic experiences. One way of ensuring best practice would be that the directions for use of each new batch of product are read carefully and then stored in a centrally placed file in the clinic, easily accessible to all members of the dental team.
cord-014687-0am4l5ms	2012	This presentation will focus on recent developments that have lead to a better understanding of the embryopathogenesis for fibropolycystic liver diseases (including choledochal cysts and Caroli disease), histopathological findings that have led to new classification systems for of pediatric vascular anomalies, technological advances and contrast agents in magnetic resonance imaging that are useful to characterize and limit the differential diagnosis of hepatic masses. Disclosure: Dr. Annapragada has indicated that he is a stock holder and consultant for Marval Biosciences Inc. Paper #: PA-067 Cardiovascular Image Quality Using a Nanoparticle CT Contrast Agent: Preliminary Studies in a Pig Model Rajesh Krishnamurthy, Radiology, Texas Children''s Hospital, rxkrishn@texaschildrens.org; Ketan Ghaghada, Prakash Masand, Abhay Divekar, Eric Hoffman, Ananth Annapragada Purpose or Case Report: Image quality in a separate study using a long circulating, liposomal-based nanoscale blood pool iodinated contrast agent (NCTX) suggests clinical utility in pediatrics, potentially reducing difficulties in contrast-CT of children with congenital heart disease (CHD) including the size of intravenous cannula, need for accurate timing, inability to simultaneously opacify multiple targets of interest (requiring repeated contrast administration and/or repeated imaging).
cord-015334-8p124rwp	2008	Based on the results of the pharmacoeconomic analysis, development of clinical pharmacy and CIVAS for some drugs will be discussed with the paediatric department Background and Objective: Studies show that up to 38% of patients starting treatment with antidepressants fill only a single prescription at the pharmacy, apparently not accepting treatment. Main Outcome Measures: Data collected were: nurses'' profile (age, length of service, competencies'' self-assessment), knowledge on drugs prescribed to their patients (usage, administration, side-effects, drug interactions…), use of existing tools (i.e. drugs database) and possible tools to be developed by the pharmacy ward to help them in their daily practice. The objectives were:(1)To identify the most relevant minor ailments, agreeing on the specific criteria for referral to the GP.(2)To select the non-prescription drugs, with evidence of safety and effectiveness, for the treatment of the identified minor ailments Design: Qualitative study with an expert panel which was made up of 2 primary care physician from SEMFYC and six community pharmacists (two members of SEFAC and four members of GIAF-UGR).
cord-017331-ru7mvfc0	2017	The chapter includes history, etiology, susceptible hosts, transmission, pathogenesis, clinical symptoms, lesion, diagnosis, zoonosis, Treatment and control strategy of Tuberculosis, Salmonellosis, Chlamydiosis, Campylobacteriosis, Lyme disease, other bacterial infection, Newcastle disease, Avian Influenza infection, West Nile Virus infection, Usutu virus infection, Avian Borna Virus infection, Beak and feather disease, other viral infection, Toxoplasmosis, Giardiasis, Cryptosporidiosis, other parasitic infection, Cryptococcosis, Aspergillosis, Other fungal infections. Clinical samples include faeces or cloacal swabs, blood/serum of live birds and affected tissues, such as liver, spleen, heart, intestine/caeca, lung, esophagus/crop, brain and kidney in 10% buffered formalin. Non-specific clinical symptoms such as neurological signs (head between legs), depression, ruffled feathers, and standing at the bottom of the cage are observed in pet birds with AIV infection (Fig. 2.13) . The virus is detected in brain, heart, liver, kidney, lungs, and intestinal tissues of laboratory mice and naturally infected birds.
cord-018335-4l7scdqk	2016	In preparation for the shift from fee-for-service to a valuebased payment system [ 15 ] large community hospitals have been actively engaged in three enterprises which will impact laboratory test utilization: buying physician practices, increasing the use of hospitalists and consolidation of hospitals. Certainly, utilization management of POCT programs will require investigations to determine the relationship between total laboratory turn-around time for results, patient outcome and hospital costs using cost effectiveness analyses [ 36 ] . As technology advances, the traditionally " agrarian society " of the laboratory is becoming more industrialized with the implementation of automation, molecular based testing, and use of mass spectrometry ( MALDI-TOF -Matrix-Assisted Laser Desorption Ionization-Time of Flight). However, all of these technological advances are shortening the time for a laboratory diagnosis and ultimately maximizing the impact to patient care and how physicians at a large community hospital will utilize the more rapid microbiology laboratory services.
cord-021453-vf8xbaug	2007	The use of dogs continued as biomedical research advanced, and they were featured in many noteworthy studies, including those by Pavlov to observe and document the conditioned reflex response and by Banting and Best to identify the role of insulin in diabetes mellitus. Especially noted in this chapter are infectious diseases associated with the use of random-source dogs that have unknown vaccination history and have had intensive contact with other similar animals at pounds and/or shelters, or conditions seen frequently in the beagle, the most common breed used in biomedical research. Culture requires selective isolation media, and growth is favored by reduced oxygen tension and a temperature of 42~ Any disorder that can cause diarrhea in dogs should be considered as a differential diagnosis, including canine parvovirus, coronavirus, distemper virus, Giardia, and Salmonella infections; helminth infestations; and hemorrhagic gastroenteritis.
cord-021494-9glqvzfx	2012	The mental construct of etiology (cause), pathogenesis (progression), natural history (clinical outcome), and response to therapy is the standard approach for pathologists thinking about a disease. Diagnostic pathology will continue to use morphology and complementary data from protein (immunohistochemical) and nucleic acid (cytogenetics, in situ hybridization, DNA sequence, and RNA abundance) screening assays. It is possible that each new neoplasm will be promptly defined as to ploidy, translocations, gene copy number differences, DNA mutations, and RNA expression cluster subset, allowing residual disease screening as well as individualized therapy. Pathologists diagnose disease by generating a differential diagnosis, then finding the best fit for the clinical presentation, the radiographic appearance, and the pathologic (both clinical lab and morphologic) findings. Pathologists diagnose disease by generating a differential diagnosis, then finding the best fit for the clinical presentation, the radiographic appearance, and the pathologic (both clinical lab and morphologic) findings.
cord-021555-rrverrsj	2007	These references also provide information regarding vaccination products licensed for use in ruminants and typical herd and flock vaccination parasite control schedules ("Current Veterinary Therapy," 1986 , 1999 "Council report," 1994; "Large Animal Internal Medicine," 1996; Smith and Sherman, 1994) When designing a vaccination program during qualification of a source or at the research facility, it is important to evaluate the local disease incidence and the potential for exposure. Clinical signs in chronic cases in older animals, such as adult goats, include soft stools, weight loss, anorexia, depression, and severe diarrhea, sometimes with mucus and blood. This pathogen does present a complication due to the carrier status of some animals, the likelihood of herd outbreaks, the severity of disease in younger animals, and the morbidity, possible progression to uveitis, and time and treatment costs associated with infections.
cord-022034-o27mh4wz	2009	They include presence of disease outbreaks of the same illness in noncontiguous areas, disease outbreaks with zoonotic impact, different attack rates in different environments (indoor versus outdoor), presence of large epidemics in small populations, increased number of unexplained deaths, unusually high severity of a disease for a particular pathogen, unusual clinical manifestations owing to route of transmission for a given pathogen, presence of a disease (vector-borne or not) in an area not endemic for that particular disease, multiple epidemics with different diseases in the same population, a case of a disease by an uncommon agent (smallpox, viral hemorrhagic fevers, inhalational anthrax), unusual strains of microorganisms when compared to conventional strains circulating in the same affected areas, and genetically homogenous organisms isolated from different locations.
cord-022203-t2f0vr1w	2009	Clinical signs are often non-specific and include fever, anorexia and weight loss. Gastrointestinal signs are uncommon in cats compared to dogs, and include chronic diarrhea, mesenteric lymphadenopathy and anorexia. • Dysfunction of any organ system may result from granuloma formation within the tissue of that organ, e.g., liver, kidney, spleen, intestines, lungs, etc., however, organ failure producing clinical signs only rarely occurs, and most dysfunction is only detected on biochemical tests. Clinical signs in the acute, fatal form of extraintestinal disease are caused primarily by tissue damage from the rapidly dividing tachyzoites. • Young kittens are more likely to have gastrointestinal signs, although mild clinical disease has been reported in adult cats as well. Systemic signs, which are not present in all cats, include fever, anorexia, lethargy, vomiting, diarrhea and lymphadenopathy. Systemic signs such as fever, anorexia and depression are commonly reported (44% of cats) and can be seen with skin lesions.
cord-022467-j2trahab	2009	A recent clinical trial that included children over age 12 years and used a fixedcombination homeopathic remedy for a mean 4.1 days of treatment reported that 81.5% reported subjective feelings of being symptom free or significantly improved without complaint of any adverse side effects. 4 A randomized, double-blind, placebocontrolled study from Great Britain of 170 children with a starting median age of 4.2 years in the experimental group and 3.6 years in the placebo group concluded that individually prescribed homeopathic remedies seem to be ineffective in reducing symptoms or decreasing the use of antibiotics in pediatric patients with URI. 414 In a nonrandomized clinical trial involving 30 children ages 3 months to 8 years with chronic diarrhea of 2 to 4 months'' duration that was unresponsive to Western medicine and TCM, individualized acupuncture treatment eliminated symptoms and normalized stools.
cord-022520-ebj51v9o	2007	Campylobacter jejuni is a gram-negative, spirally curved microaerophilic bacterium that is recognized as a significant cause of human enteritis and is as-sociated with diarrheic illness in several animal species, including dogs, cats, cows, goats, pigs, mink, ferrets, and sheep (Carter et al., 1995) . Reports of spontaneous cases in ferrets require diagnostic confirmation and differentiation from cases of proliferative bowel disease and other infectious and noninfectious causes of diarrhea. Systemic infection with the bovine strain in ferrets results in disseminated disease with weight loss, anorexia, lethargy, death, and miliary lesions involving the lungs and other viscera (Fox, 1998a) . Clinical disease may occur in kits as young as 1-4 days old or in older animals up to 6 weeks of age. Other potential etiologies that have been considered include two infectious agents that are known to cause chronic immune stimulation in affected ferrets, the Aleutian disease virus (ADV) and Helicobacter mustelae.
cord-022526-j9kg00qf	2009	Examination of the cardiovascular system (heart, peripheral pulse, and mucous membranes), lungs, and abdomen is essential to detect clinical signs of systemic inflammation from endotoxemia, coagulation disorders, dehydration, ileus, shock, and other abnormalities resulting from injury to the small or large intestine. Several reports suggest the efficacy of cisapride in managing intestinal disease in horses, including the resolution of persistent large colon impaction, treatment of equine grass sickness, and as a preventative for POI in horses after small intestinal surgery (0.1 mg/kg body mass intramuscularly during the postoperative period). 9 Primary role-players in DPJ-associated ileus include peritoneal inflammation, inflammatory cell migration/activation within the muscularis, small intestinal mechanical distention, and effects of endotoxin absorption. Diarrhea probably results from the severe ulceration and inflammation of the large intestine, causing increased secretion of water, electrolytes, and protein and decreased absorption of fluid.
cord-022555-a7ie82fs	2011	One study found that, of cats investigated for gastrointestinal disease, 9 of 33 cats (27%) had no pathology recognized proximal to the jejunum (i.e., the effective length of diagnostic endoscopes would have precluded diagnosis), and other organs were affected in 9 of 10 cats with inflammatory bowel diseases and 7 of 8 cats with intestinal small cell lymphoma. 60, 64 Quantification of serum cobalamin levels is recommended in cats with clinical signs of small bowel diarrhea, ones suspected to have an infiltrative disease of the small intestine (inflammatory bowel disease or gastrointestinal lymphoma), or ones with pancreatic dysfunction. Survey radiographs may be normal in cats with esophagitis and strictures, but are useful to rule out other causes for the clinical signs, such as a foreign body, or to detect related problems, such as aspiration pneumonia. 8, 29 Other non-neoplastic causes reported for gastric or gastroduodenal ulceration in cats include parasites (e.g., Ollulanus tricuspis, Toxocara cati, Aonchotheca putorii, Gnathostoma spp.), bacterial infections, toxins, inflammatory bowel disease, and foreign bodies.
cord-022754-ehq9qnoo	2012	Conversely, in cases of chronic end-stage liver disease, such as cirrhosis, serum hepatic enzyme activities may not be markedly increased, or may even be within the reference interval as a result of the replacement of hepatocytes with fibrous tissue. World Small Animal Veterinary Association (WSAVA) Standards for the Clinical and Histological Diagnosis of Canine and Feline Liver Disease suggest that the cytologic evaluation of bile forms part of the minimum diagnostic requirement for cats with extrahepatic cholestasis and for dogs guidance. 32 Hyperglobulinemia can be seen in dogs with cirrhosis, but it remains to be determined whether this corresponds with increased autoantibodies as occurs in humans with autoimmune hepatitis, or whether it reflects nonspecific systemic antibody production in response to antigens from the portal blood which bypass the liver through acquired PSSs. 83 Mild nonregenerative anemia may be a reflection of chronic disease.
cord-023165-f6o6owg3	2009	The most important reason for examining feces in sheep and goats is to determine the presence and relative number of nematode parasites infesting an animal or flock. Clinical signs of frothy bloat and free gas bloat from either food intake or physical obstruction of the esophagus are usually more severe and immediately life-threatening than bloat seen from rumen wall diseases and systemic influences. Rumen acidosis usually occurs in animals that have been fed predominantly forage-based rations and are suddenly given access to large amounts of highly fermentable concentrates or concentrated forms of energy. Table 4 -2 lists the agents most likely to cause diarrhea in lambs and kids, tissues or other samples required for diagnosis, and commonly employed test methods. Liver abscesses usually occur as a result of chronic rumenitis in cattle, but they are rare in sheep and goats. F. hepatica infestation usually causes acute disease in sheep and goats but can present as a chronic condition.
cord-023367-ujflw19b	2020	The cause of transformation is usually unknown; in rare cases, especially in flock outbreaks in sheep, it can be linked to exposure to the bovine leukemia virus, which has occurred experimentally and as a result of the administration of whole blood Anaplasma vaccines. C. perfringens type C in older sheep causes the disease known as "struck." Affected animals usually are found dead or with signs of toxemia. The course of the disease is usually very short (0.5-12 hours), so sudden or spontaneous death is a common clinical sign across affected small ruminant species. Additional evidence of systemic toxemia (metabolic acidosis, azotemia, and increases in liver and muscle enzymes) also may be seen; however, diagnosis of black disease is based on characteristic history (endemic liver fluke areas), clinical signs, and postmortem findings and testing.
cord-023528-z9rc0ubj	2009	First, restriction of the thorax or the abdomen can result in impaired ventilation, which can occur easily when one restrains a foal and may result in spuriously abnormal arterial blood gas values (see the discussion on arterial blood gas evaluation, Respiratory Diseases Associated with Hypoxemia in the Neonate). Hypoxic ischemic encephalopathy (HIE), currently referred to as neonatal encephalopathy in the human literature, is one systemic manifestation of a broader syndrome of perinatal asphyxia syndrome (PAS), and management of foals with signs consistent with a diagnosis of HIE requires the clinician to examine other body systems fully and to provide therapy directed at treating other involved systems. Therapy for the various manifestations of hypoxiaischemia involves control of seizures, general cerebral support, correction of metabolic abnormalities, maintenance of normal arterial blood gas values, maintenance of tissue perfusion, maintenance of renal function, treatment of gastrointestinal dysfunction, prevention and recognition and early treatment of secondary infections, and general supportive care.
cord-023913-pnjhi8cu	2011	So while there has been no shortage of effort paid to improving Medicare, the one common theme in all of the recent initiatives is that dental care has been conspicuously 1 A new study by Hedlund, Jeffcoat, Genco and Tanna funded by CIGNA of patients with Type II diabetes and periodontal disease found that medical costs of patients who received maintenance therapy were $2483.51 per year lower than patients who did not. Examples of integrated care models do exist, such as that presented by (Heuer 2007 ) involving school-linked and school-based clinics with an "innovative health infrastructure." According to Heuer, "Neighborhood Outreach Action for Health (NOAH)" is staffed by two nurse practitioners and a part-time physician to provide "primary medical services to more than 3,200 uninsured patients each year" in Scottsdale, Arizona.
cord-026009-rdhuc2n2	2009	This chapter provides information needed to diagnose and treat the most frequently encountered problems of mice, rats, gerbils, hamsters, guinea pigs, and chinchillas. • Diagnosis is based on clinical signs, history, visualization of parasite, skin scrape, and cellophane tape test. • Clinical signs in adults are caused by secondary bacterial infections and are similar to those in MRM. Common primary or secondary pathogens causing respiratory signs in mice are Streptococcus pneumoniae, Corynebacterium kutscheri, Pasteurella pneumontropica, Pseudomonas aeruginosa, and Klebsiella pneumoniae. • Mouse poliomyelitis/encephalomyelitis, also known as Theiler disease, causes clinical signs in 1 in 10,000 infected mice. • In contrast to mice, Sendai virus rarely causes clinical signs in rats. • Pneumonia in guinea pigs usually is caused by infection with S. • Diagnosis of scurvy is based on clinical signs, the exclusion of other causes of diarrhea, and response to vitamin C therapy (see Table 177 -10).
cord-026031-hnf5vayd	2009	Fresh whole blood Coagulopathy with active hemorrhage (disseminated intravascular coagulation, thrombocytopenia; massive acute hemorrhage; no stored blood available) Stored whole blood Massive acute or ongoing hemorrhage; hypovolemic shock caused by hemorrhage that is unresponsive to conventional crystalloid and colloid fluid therapy; unavailability of equipment required to prepare blood components Packed red blood cells Nonregenerative anemia, immune-mediated hemolytic anemia, correction of anemia before surgery, acute or chronic blood loss Fresh frozen plasma Factor depletion associated with active hemorrhage (congenital: von Willebrand''s factor, hemophilia A, hemophilia B; acquired: vitamin K antagonist, rodenticide intoxication, DIC); acute or chronic hypoproteinemia (burns, wound exudates, body cavity effusion; hepatic, renal, or gastrointestinal loss); colostrum replacement in neonates Frozen plasma Acute plasma or protein loss; chronic hypoproteinemia; (contains stable colostrum replacement in neonates; hemophilia B and clotting factors) selected clotting factor deficiencies Platelet-rich plasma* Thrombocytopenia with active hemorrhage (immune-mediated thrombocytopenia, DIC); platelet function abnormality (congenital: thrombasthenia in Bassett hounds; acquired: NSAIDs, other drugs) Cryoprecipitate
cord-029332-yn603pvb	2020	Included are cases of Brugada type I pattern positivization (1) in the context of fever, one of the most common presenting symptoms of the disease (2); electrical ventricular storm (3); transient atrioventricular block in the absence of myocarditis (4); sinus node dysfunction requiring pacemaker implantation (5) ; and finally a provocative report on the use of amiodarone as a possible treatment for COVID-19 (6) . In addition to cases of direct myocardial injury, some with pathological evidence, we also present 2 cases of takotsubo cardiomyopathy (16, 17) Two cases highlight the special circumstances faced by patients with left ventricular assist devices (18, 19) , which include the inability to tolerate prone positioning to augment respiratory support because of the mechanical equipment and the hypothesis that mechanical circulatory support may provide a type of protection against the most serious hemodynamic consequences of severe acute respiratory syndrome coronavirus-2 infection.
cord-029547-9ei1ram3	2020	According to the Diagnosis and Treatment Program of Novel Coronavirus Pneumonia, only a suspected case has one of the pieces of evidence of etiology or serology, such as positive nucleic acid, confirmation of gene sequencing, and virus specific antibody, to be confirmed to be COVID-19 patient, 55 and the suspected cases were identified by a comprehensive analysis of epidemiological history and clinical manifestations. 64 There have been tens of clinical trials to confirm the safety and efficiency of chloroquine in treating COVID-19 patients, and its mechanism can be described as interfering with the glycosylation of ACE2 or alkalizing the phagolysosome to inhibit viral replication, 65, 66 which prevents the SARS-Cov-2 entering the host cells. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial
cord-031188-btrc3k4c	2020	However, the education and training for pharmacists provided in the country are not sufficient enough for optimum patient care and for delivering clinical pharmacy services. International collaborations in terms of faculty and student exchanges, preceptor training, and accreditation by international organizations such as Accreditation Council for Pharmacy Education (ACPE), establishment of need-based curriculum, incorporating clinical pharmacy department under the organizational structure of hospitals, etc., may be the right approaches to improve the current status of clinical pharmacy education in the country. 7, 8 Clinical pharmacy service is provided by the pharmacist who possesses specialized advanced education and training and works in collaboration with other health care professionals. Awareness among other health care professionals and hospital management on the importance of clinical pharmacy services should be the starting point of change to achieve excellence in clinical pharmacy practice in Nepal.
cord-034340-3ksfpaf7	2020	Objectives: The current study was undertaken to evaluate sociodemographic and sociocultural features, parent behavior, the gestation and breastfeeding period, nutritional status of early childhood in our patients with JIA, and to determine their relationship with disease activity, damage index, remission time, and relapse rate. Methods: In the present study were included data 170 JIA(55 boys and 115 girls)aged from 2 to 17 years,who received scheduled vaccination before the age of 2 years and before JIA onset against measles,parotitis,diphtheria and rubella.Incomplete vaccination means the reduced number of vaccine to age.In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA.JIA categories were:oligoarthritis -73,polyarthritis -61,systemic-16 and enthesitisrelated arthritis-20.Data presented with median and 25%>75% Results: Incomplete vaccination against MMR was in 50 (42%)diphtheria in 85 (50%) of the JIA patients.
cord-253295-82ydczid	2020	Patient workup uses present illness history with reference to past medical history, review of other organ systems for other abnormalities, review of family history, physical examination, radiographic studies, clinical laboratory studies (for example, peripheral blood or CSF specimens), and anatomic pathology laboratory studies (for example, tissue biopsy or pleural fluid cytology specimens). Obviously, arrival at the correct diagnosis is a function of the examining physician and pathologist (fund of knowledge, experience, alertness), the prevalence of the disease in question in the particular patient (age, race, sex, site), and the sensitivity/ specificity of the screening tests used (physical exam, vital signs, blood solutes, tissue stains, genetic assays). However, understanding the molecular and cellular pathogenesis of a disease allows development of screening methods to determine risk for clinically unaffected individuals, as well as mechanistic approaches to specific therapy.
cord-255139-hswef5ky	2018	This article provides a display table laying out the differential diagnosis of common acute toxicologic versus nontoxicologic illnesses in small animals. Upon presentation of an acutely ill animal, a veterinary professional must consider poisoning as a potential cause among the differentials. Before obtaining a complete case history, the first goal should be to stabilize the patient and preserve life of the acutely ill animal irrespective of the cause. A majority of clinical cases on presentation are treated supportively as only a very few specific antidotes are available or needed for treating specific poisonings. Other samples for toxicology testing in a diagnostic laboratory include whole blood for heavy metal analysis (lead), blood cholinesterases (organophosphate poisoning), and presence of pesticides (anticoagulant rodenticides). Table 1 outlines some important toxicologic versus nontoxicologic rule-outs based on clinical abnormalities one must consider in an acutely ill animal. An acutely ill animal with sudden onset of clinical effects may often have multiple major clinical signs/abnormalities present.
cord-255140-3dwqqgv1	2013	Although some experts state that the risk of a largescale bioterrorist attack is low, 7 in a more recent analysis, US Senators Graham and Talent quote their conclusion form the Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism in 2010, which stated "unless the world community acts decisively and with great urgency, it is more likely than not that a [biologic] weapon of mass destruction will be used in a terrorist attack somewhere in the world by the end of 2013." 8 Anthrax in particular remains such a concern, because of both the lethality of the agent and also the potential availability given the number of governments that produced weaponized anthrax in the past. The mode of deployment as a biological weapon in the past has often been through infected vectors 22 ; however, a modern bioterrorist would most like deploy the agent via aerosolization and it could present as: primary pneumonic tularemia (inhalation), oculoglandular tularemia (eye contact), ulceroglandular (broken skin contact), or oropharyngeal (mucous membrane contact without deep inhalation).
cord-255746-ir73lpi8	2020	CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. While several reports on tocilizumab treatment in COVID-19 patients now exist, data pertaining specifically to tocilizumab use in a large cohort of critically ill patients on invasive ventilation is lacking (11, 12) . Thus, in this report, we describe the 21-day outcomes of mechanically ventilated patients with severe COVID-19 who received tocilizumab as part of their management strategy. Our report of tocilizumab in patients exclusively receiving invasive mechanical ventilation demonstrates a 21-day mortality of 21% and clinical improvement at day 21 in 58% of patients with severe disease. Preliminary data from the placebo-controlled trial of remdesivir, which subsequently led to its emergency use authorization by the FDA for treatment of severe COVID-19, do not demonstrate differences in recovery or mortality rates between the remdesivir and placebo groups among patients on invasive ventilation (21) .
cord-258029-gyvg7ffa	2020	title: Favipiravir-based regimen for coronavirus disease 2019 pneumonia for a 47-day-old male newborn A 47-day-old, asymptomatic male newborn of coronavirus disease 2019 infected mother tested positive for coronavirus disease 2019 by reverse transcription polymerase chain reaction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing coronavirus disease 2019 (COVID19) , which emerged in Wuhan, Hubei Province, China, in mid-December 2019 to become pandemic disease. A 47-day-old, male newborn was asymptomatic but had household contact with his COVID-19 infected mother. A favipiravir-based regimen may be the drug of choice for COVID-19 pneumonia in the newborn, safe and tolerable in short-term use, but more evidence is needed to assess the effects of long-term treatment. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China
cord-258049-l55mx4lp	2015	We performed a prospective, multicenter, multiyear study [10] [11] [12] to examine the typical inpatient clinical course of and to develop hospital discharge guidelines for children age <2 years hospitalized with bronchiolitis. A child was considered clinically improved on the earliest date he/she met all of the following criteria: (1) none or mild retractions and improved or stable retractions compared with the previous inpatient day; (2) daily estimated average respiratory rate (RR) <60 breaths per minute for age <6 months, <55 breaths/minute for age 6 to 11 months, and <45 breaths/minute for age 12 months with a decreasing or stable trend over the course of the current day; (3) daily estimated average RAO2 saturation 90%, lowest RAO2 saturation 88% 21 ; and (4) not receiving intravenous (IV) fluids or for children receiving IV fluids a clinician report of the child maintaining oral hydration.
cord-258281-gxwk8jq9	2020	Based on recently published literature and official documents, this review provides an introduction to the pathogenesis, pathology, and clinical features of COVID-19 and has focused on the current researches on clinical features, pregnancy outcomes and placental histopathological analysis from pregnant women infected with SARS-CoV-2 in comparison with SARS-CoV and MERS-CoV. Although there is no unequivocal evidence to support the fetal infection by intrauterine vertical transmission of SARS, MERS and SARS-CoV-2 so far, more and more articles began to report maternal deaths due to COVID-19. There were no cases of vertical transmission identified among pregnant women infected with SARS 44-49 so far, but SARS during pregnancy is associated with high incidences of spontaneous miscarriage, preterm delivery, intrauterine growth restriction, endotracheal intubation and admission to the neonatal intensive care unit [44] [45] [46] . This is a review on pregnant women infected by SARS-CoV-2, SARS, and MERS, including their pathogenesis, clinical manifestations and pregnancy outcomes. Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy: report of two cases & review of the literature
cord-260993-udajtsmm	2020	Meta-regression analysis was employed using OpenMeta Analyst software, taking into consideration the following study characteristics; sample size, mean age of patients, percentage of males, city of the hospital, publication date, and quality score. We applied TSA on mortality rate available among all eligible articles of COVID-19 patients with a mild and severe exhibition and indicated that the cumulative Z-curve transverses the monitoring boundaries before reaching the required sample size and achieving considerable significant and so no further studies are necessary (Figure 2 ). Our meta-analysis including 3428 subjects from 20 retrospective studies explored the potential relationship between liver injury and the severity of COVID-19 disease. 32 A recent study reported that the liver injury observed in COVID-19 patients might be caused by lopinavir, which is used as an antiviral for the treatment of SARS-CoV-2 infection. In this meta-analysis, we comprehensively analyzed liver dysfunction in accordance with the severity of clinical outcomes in COVID-19 patients.
cord-262784-r9gq2oan	2020	title: Clinical Characteristics and Reasons for Differences in Duration From Symptom Onset to Release From Quarantine Among Patients With COVID-19 in Liaocheng, China Methods: We analyzed retrospective data regarding general characteristics, epidemiologic history, underlying chronic diseases, clinical symptoms and complications, chest computed tomography findings, biochemical monitoring, disease severity, treatments, and outcomes among 37 adult patients with COVID-19. Patient diagnosis, release from quarantine, and disease severity among all cases were determined according to the "Protocol for the Diagnosis and Treatment of Novel Coronavirus Pneumonia" issued by the National Health Commission of the People''s Republic of China and the National Administration of Traditional Chinese Medicine (8, 9) . The present study retrospectively analyzed the general characteristics, epidemiological history, chronic underlying diseases, clinical symptoms, complications, chest computed tomography (CT) findings, biochemical features, disease severity, treatment plans, and outcomes of 37 patients.
cord-262843-i0cy7467	2008	Patients with acute pharyngo-tonsillitis were evaluated for causative pathogens and were assessed clinical symptoms and pharyngo-tonsillar finding by a clinical scoring system. CONCLUSION: The current study strongly suggested that the clinical scoring system reflected disease severity well and would be very useful for evaluating clinical course and decision making for the antimicrobial treatment of acute pharyngo-tonisllitis. An appropriate scoring system was also developed and applied for evaluating severities and clinical course of acute pharyngo-tonsillitis. In the current study, we defined causative pathogens and the severity of acute pharyngotonsillitis by a clinical scoring system in adult patients. In this study, the frequencies of viruses in adult acute pharyngo-tonsillitis were lower rather than those reported in children, when we applied PCR/RT-PCR to identify four important viruses such as RS virus, adenovirus, influenza virus, and hMPV from pharyngeal swab.
cord-263936-8yud5o6c	2020	While reduced clinical imaging volume and mandates to maintain physical distancing presented new challenges to traditional medical education during this period, new opportunities developed to support our division in providing high-quality training for residents and fellows. The Accreditation Council for Graduate Medical Education (ACGME) Core Competencies for Diagnostic Radiology helped guide division leadership in restructuring and reframing breast imaging education during this time of drastic change and persistent uncertainty. Here, we reflect on the educational challenges and opportunities faced by our academic breast imaging division during the height of the COVID-19 pandemic across each of the ACGME Core Competencies. Prior to the pandemic, all fellows participated in daily team huddles held in the diagnostic imaging clinic at 8:00 AM, which were attended in-person by all in-house personnel that day including assistants, technologists, and practice managers.
cord-266469-n484zqq1	2020	title: Lung base CT findings in COVID-19 adult patients presenting with acute abdominal complaints: case series from a major New York City health system Data is rapidly emerging given the novel nature of this devastating disease, with a paucity of published reports investigating abdominal presenting symptoms and subsequent CT imaging findings in COVID-19 patients. The purpose of our study is to describe the demographic, clinical, biological, and lung base CT findings in COVID-19 patients presenting with acute abdominal complaints, either in isolation or in combination with respiratory complaints. In this study, we described demographic, clinical, biological, and lung base CT findings in a population of COVID-19 patients who presented to our Health System with acute abdominal complaints, either in isolation or in combination with respiratory complaints. In conclusion, we report demographic, clinical, biological, and lung base CT findings in a group of patients presenting to our Health System with acute abdominal complaints who were found to have COVID-19.
cord-266730-mio282vy	2020	We statistically analyzed the clinical symptoms and laboratory results of COVID‐19 patients and explained the discharge rate and fatality rate with a single‐arm meta‐analysis. The results of the random effects model meta-analysis showed that the fatality rate of the COVID-19 patients was 5% (95% CI 15, 27 found that the fatality rate of patients with viral pneumonia increased when they had a basic disease and mixed bacterial infection, which was consistent with the results of our study. Epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside Wuhan, China Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia COVID-19 patients'' clinical characteristics, discharge rate, and fatality rate of meta-analysis
cord-267608-0odu8lus	2020	Accordingly taking the advantage of interim analysis based on novel biomarker approach for detecting the pathogenesis-specific molecular alteration(s), an adaptive clinical study can select the drug-sensitive sub-population from patients with initially targeted disease or an alternative indication, to continue the investigation for an optimized therapeutic efficacy [7] . While human bioequivalence study is increasingly contributing to evaluation of emerging formulation and bio-similar agents besides chemical generics [4] , several adaptive trial designs have been capable of translating the scientific breakthroughs into novel therapeutic benefits with shorter processing time and lower financial costs, to address the unmet clinical needs [3, 19] . Of note, to preserve the strength of clear defining efficacy and safety of tested drugs, the innovative designs of clinical study are substantially overlapped with classic trial protocols of three phases which still serve as the mainstream approach of clinical investigation [3, 7] .
cord-272727-a5ngjuyz	2020	Specifically, we propose a comprehensive data-driven approach to understand the clinical characteristics of COVID-19, predict its mortality, forecast its evolution, and ultimately alleviate its impact. Each column reports 128 cohort-level statistics on demographics (e.g., average age, gen-129 der breakdown), comorbidities (e.g., prevalence of diabetes, 130 hypertension), symptoms (e.g., prevalence of fever, cough), 131 treatments (e.g., prevalence of antibiotics, intubation), lab 132 values (e.g., average lymphocyte count), and clinical outcomes 133 (e.g., average hospital length of stay, mortality rate). The models with lab values provide 309 algorithmic screening tools that can deliver COVID-19 risk 310 predictions using common clinical features. These findings 333 are also in agreement with clinical reports: an elevated CRP 334 generally indicates an early sign of infection and implies lung 335 lesions from COVID-19 (27), elevated levels of leukocytes 336 suggest cytokine release syndrome caused by SARS-CoV-2 337 virus (28), and lowered levels of serum calcium signal higher 338 rate of organ injury and septic shock (29) .
cord-273973-3uxg97tu	2019	Always consider previous microbiological data and local epidemiology with regards to empiric antibiotics CAP should include empiric coverage for atypicals along with community-associated organisms HAP and VAP should include broad gram-positive coverage, especially MRSA, along with broad gram-negative coverage, including ESBLs and CREs if warranted Influenza is the only virus with approved treatment, oseltamavir; therefore, this should be started empirically if there is a concern Antifungals should not be started empirically, even in lung transplant recipients; however, fungal infections should be worked up thoroughly pathogen, source control, and adjustment of immunosuppression is the hallmark of treatment. Always consider previous microbiological data along with local epidemiology with regards to empiric antibiotic decisions Asymptomatic bacteriuria should only be treated in renal transplant patients during the first month posttransplantation Antimicrobials should be tailored to the causative agent, with durations that generally range from 7 to 21 days depending on the clinical context Fluconazole is the treatment of choice for cystitis and pyelonephritis if Candida is the causative organism
cord-274283-ukhgs6z1	2020	INTRODUCTION: Numerous case series have reported on the baseline characteristics and in-hospital mortality of patients with COVID-19, however, these studies included patients localized in a specific geographic region. Numerous case series have reported on the baseline characteristics and in-hospital mortality of patients with COVID-19, however, these studies included patients localized in a specific geographic region. Numerous case series have reported on the baseline characteristics and inhospital mortality of patients with COVID-19, however, these studies included patients localized in a specific geographic region [3] [4] [5] [6] [7] [8] . We included studies that had more than ten adult patients ([ 18 years), and reported clinical characteristics of patients diagnosed with laboratory-confirmed COVID-19, along with all-cause mortality as one of the outcomes. Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): early report from the United States Clinical Characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: a single-centered, retrospective study
cord-274481-k1dp1ilv	2020	Summary of the evidence: the systematic review identified three comparative clinical trials with available data on the effects of hydroxychloroquine (HCQ) in COVID-19 patients: two open randomized clinical trials (29, 30) in a patient population with mild to moderate disease, and one cohort study. Recommendation 2 -we suggest against the routine use the hydroxychloroquine or chloroquine plus azithromycin combination for treatment of COVID-19 patients (weak recommendation; Level of Evidence very low). Recommendation 4 -We suggest the use of empirical oseltamivir treatment in patients with Severe Acute Respiratory Syndrome (SARS) or flu-like syndrome with risk factors for complications when a diagnosis of influenza cannot be ruled out (weak recommendation; Level of Evidence very low). Summary of the evidence -two randomized clinical trials assessed the use of lopinavir/ritonavir in COVID-19 patients.
cord-274802-7ioiwsd8	2020	Proteomic and transcriptomic studies on bronchoalveolar lavage (BAL) samples from COVID-19 patients have also revealed considerable insights into the expression of SARS-CoV-2 receptors, co-receptors, immune responses, as well as risk factors for severe disease e.g. age and co-morbidities. Furthermore, treatment with a recombinant C5a antibody on 2 male COVID-19 patients aged 54 and 67 years showed significant benefit in suppressing complement hyperactivation, which contributes to the excessive immune response causing aggravated inflammatory lung injury, a hallmark of SARS-CoV-2 pathogenesis and lethality (242) . Consistent with endothelial injury, the significantly elevated levels of von Willebrand factor found in the patient with severe COVID-19 has led to the idea that the infection of the ACE2 expressing endothelium by SARS-CoV-2 induces injury and activates the complement , which sets up a feedback loop that maintains a state of inflammation (243, (268) (269) (270) . Initial clinical studies in China involving 100 SARS-CoV-2 infected patients, who were treated with Chloroquine, showed amelioration of pneumonia, shortened disease progression, increased resolution of lung lesions on CT, and a better virus-negative conversion (313, 314) .
cord-276255-0ofsa40u	2020	OBJECTIVE: This study aimed to explore the impact of the COVID‐19 pandemic on hospital‐based clinical pharmacists working in Malaysia and the implications on how clinical pharmacy is perceived as a health care service. Clinical pharmacists in Malaysia are pharmacists who have been assigned to work in the hospital wards, where they provide pharmaceutical care to patients and support the health care team with information and guidance for the effective use of medicines. This study aims to explore the impact of the COVID-19 pandemic on hospital-based clinical pharmacists in Malaysia and the implications on how clinical pharmacy is perceived as a health care service. The coding and subsequent analysis of the findings of this study led to the development of 3 main themes: ''Reassignment and other changes in clinical pharmacist roles'', ''Adapting clinical pharmacy services to COVID-19'', and ''The need for clinical pharmacists in the ward''.
cord-276495-q22jnkn2	2020	This type of immunological memory or epigenetic programming to a pre-activated state allows the generation of a sustained and more effective non-specific response, even after years, although in the protocols of these studies, the innate immunity was evaluated after 3 months (2). Various clinical trials are underway to evaluate trained immunity through BCG vaccination in healthy volunteers under the coordination of Dr. Mihail Netea (Radboud University Medical Center, Nijmegen, the Netherlands). To our knowledge, there are no published articles or clinical evidences that show that BCG immunization protects against SARS-CoV-2 in Brazil. The journal The Lancet, in May 2020, published the results of an observational, longitudinal, and retrospective clinical study based on medical records of COVID-19 patient cohorts treated across 6 countries and 671 hospitals, with different technical capabilities and diverse drug protocols (13) .
cord-276740-4wwo9tho	2020	The present article summarizes the results from the 3rd annual psychotherapy award program designed to highlight the valuable contributions made in eleven different categories. It seems important to highlight the contributions being made by psychotherapists each year, recognizing heroes within the field of mental health providers, who work quietly to help improve the lives of their patients. In terms of measures used in the research, psychological assessment in clinical settings often relies on a combination of self-report questionnaires, structured diagnostic interviews, and possibly other sources such as informant reports or observational measures, often completed on several occasions over the course of therapy (Overholser 2014b ). This award highlights the value of a comprehensive approach to psychotherapy, highlighting the contribution made through a published article that encourages an integrative approach to psychological treatments. The present award highlights some useful ideas and innovative strategies that can help clinicians to incorporate contemporary technology to improve their clinical services.
cord-277528-t0tglg0a	2020	title: Clinical placements for undergraduate diagnostic radiography students amidst the COVID-19 pandemic in Singapore: Preparation, challenges and strategies for safe resumption Coordinated preparation plans and strategies between the university and hospitals were needed to safely resume clinical placements within national and hospitals'' risk control measures against COVID-19 transmission. It is important to put into context how SIT and SGH prepared the students for the 57 challenges and designed strategies for safe resumption of clinical placements. This 80 communique was developed for all SIT Health and Social Science (HSS) students in 81 preparation for their clinical placement resumption and had all elements of risk control 82 measures for students'' compliance. SIT and SGH have collaborated in 304 many aspects of clinical placements, namely managing students'' well-being, meeting 305 learning outcomes and adhering to national and HCIs'' risk control measures through the use 306
cord-279255-v861kk0i	2020	Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID19) , emerged in late 2019, and it has posed a global health threat, causing an ongoing pandemic in many countries and territories (1) . Health workers worldwide are currently making efforts to control further disease outbreaks caused by the novel CoV (originally named 2019-nCoV), which was first identified in Wuhan City, Hubei Province, China, on 12 December 2019.
cord-279559-mob8dbcr	2020	In the context of Covid‐19, key issues include providing support to clinical trials in low‐ and middle‐income countries, without taking needed resources away from other critical clinical and public health needs; designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; supporting studies designed to improve outcomes in high‐risk environments, such as nursing homes and group homes for the developmentally disabled; and ensuring that the medical products resulting from research are made available throughout the world at an affordable price. 6 The global community must commit to supporting clinical trials in LMICs that contribute to the development of locally relevant interventions, while also ensuring that these efforts do not take resources away from other critical clinical and public health needs. 10 These and other strategies to overcome racial disparities in research will be particularly important in Covid-19 clinical trials, given that the disease is infecting and killing African Americans at a disproportionately high rate.
cord-280093-w71e0ex9	2020	BACKGROUND: Clinical trial monitoring is an essential activity for quality assurance (QA) to ensure the protection of human rights and the reliability and transparency of the data collection process. Monitoring in the context of a clinical trial entails many types of systematic activity to ensure that the study is conducted and data are acquired according to the planned protocol in compliance with Good Clinical Practice (GCP) and relevant legislation. The main roles of a monitor are defined by GCP, and are classified according to the principal purpose of monitoring as follows: first, they must ensure protection of human rights during the trial by checking that all study participants have provided written informed consent; second, they must ensure that the data collected are accurate and complete by checking the source documents; and third, they must confirm whether or not the study is conducted Essential documents for evaluation of trial conduct and the quality of the study data according to ICH-GCP 2 need to be updated and kept secure in the research institution and sponsor site in a timely manner.
cord-280431-tuzdng4h	2008	The triggers for this rapid growth have not only been recent technological developments in terms of personal computer power, but primarily clinical educators believing in the potential of simulation training approaches to help others effectively acquire life-saving skills in a safe and controlled environment. At the same time, I assumed responsibility for the development of the University of Hertfordshire''s Intensive Care and Emergency Simulation Center concentrating primarily on delivering simulation-based training to nursing and paramedical students and evaluating the teaching effectiveness of this approach [6] . Similarly, you can greatly contribute to the success of your center''s simulation programs by effectively communicating with other educators to refine scenarios provided to your participants, develop the simulation environment and new props. You might be able to use your skills and technical knowledge to further develop their ideas and improve aspects of the simulation training experience of participants.
cord-281391-0qkku2jd	2020	COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, was first identified in the Hubei Province of China in late 2019. Because of these findings, chloroquine and hydroxychloroquine were used as early therapies in the treatment of COVID-19, and its use was further propagated by a small, retrospective, biased study from France with 36 patients which showed decrease in viral burden, and improved outcomes in patients treated with hydroxychloroquine [17] . A retrospective study from the Veterans Affairs, looked at hospitalized patients who received hydroxychloroquine and showed no evidence that use of hydroxychloroquine reduced the risk of progression of disease including mechanical ventilation and death [20] . Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial
cord-282131-wap7lo05	2020	Since the outbreak of the COVID-19 epidemic in December 2019, the "Diagnosis and Treatment Scheme for Coronavirus Disease (Trial Version 5)" [6] recommended that suspected cases with pulmonary imaging characteristics be included for the first time in "clinical diagnosis" in Hubei Province. The "Diagnosis and Treatment Scheme for Coronavirus Disease (Trial Version 4)" stipulates that [22] JRID198_proof ■ 26 April 2020 ■ 3/ 8 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 a patient who meets any one of the epidemiological history criteria and any two of the clinical manifestations can be included in suspected cases, and that an etiological test then be conducted.
cord-282202-q2q4vies	2020	DESIGN: A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics). "Learning is difficult in the midst of an emergency" [7] , but our ability to deliver timely, high-impact clinical research, relevant to patients and populations, is critical across the academic spectrum [8] , from "bench to bedside to big data", whether basic biology, repurposed and novel therapeutic approaches, vaccines or modelling. Our aims were to: (i) model potential impact of the pandemic on clinical academic capacity in England relating to COVID-19; and (ii) develop evidence-based recommendations to inform the optimal scientific response to COVID-19.
cord-282261-wcmc5mh6	2020	The COVID-19 crisis affects every aspect of clinical trial research engagement including: recruitment and retention; ability to ensure participant safety while engaged in experimental interventions; study procedures, including consideration of remote assessments, impact on populations with health disparities, and generalizability of future results; outcome measures, including biomarker assessment; impact on the clinical trial workforce, including attrition; impact on dissemination of results and scientific collaborations, which move the clinical trial infrastructure forward; current and future funding allocations; and regulatory considerations in regards to management of altered study conduct and change of outcome measures (Fig. 1) . The purpose of this article is to highlight the impact of disasters such as the COVID-19 pandemic on geriatric clinical trials research and propose approaches for the scientific community to continue pushing forward. The vulnerability of older adults to COVID-19 is a critical reminder for the need to prepare for disasters during clinical trial design.
cord-282298-8tcw3cll	2012	The clinical achievements mainly include the following three: innovating methodology of disease-syndrome combination, excavating the classical theory in traditional Chinese medicine (TCM), preventing and curing refractory diseases. The development ideas and strategies of integrative medicine for future mainly include (a) standing on frontier field of international medicine and improving the capability of preventing and curing refractory diseases; (b) moving prevention and control strategy forward and improving the curative effect of common and frequent disease; (c) excavating the classical theory of TCM and broadening the treatment system of modern medicine; (d) improving the innovation level of new high effective drugs on the basis of classical prescriptions and herbs in TCM; (e) rerecognizing the theory of formula corresponding to syndrome in TCM and enhancing the level of clinical research evidence based on evidence-based medicine.
cord-283202-5fq1wxz8	2009	This article reviews the clinical signs, pathophysiology, diagnosis, treatment and prognosis of four important systemic diseases with neurological consequences: feline infectious peritonitis, toxoplasmosis, hypertension and hepatic encephalopathy. A presumptive diagnosis is based on a combination of clinical signs, evidence of recent or active infection (gained via serology for immunoglobulins or immune complexes, or PCR), exclusion of other disease processes, and response to therapy. Consequently, affected cats often demonstrate signs relating to renal disease or hyperthyroidism, given the high prevalence of hypertension with these disorders. Hepatic encephalopathy is the clinical syndrome of abnormal neurological function caused by portosystemic shunting, with or without intrinsic liver disease. Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats Non-invasive blood pressure measurements in cats: clinical significance of hypertension associated with chronic renal failure
cord-283545-vu8lt3w6	2011	Although guinea pigs are sensitive and susceptible to the development of lesions from a wide range of viruses, bacteria, protozoa, and parasites, only a small number of organisms cause natural infection and only a portion of that group cause clinical disease. Although guinea pigs are sensitive and susceptible to the development of lesions from a wide range of viruses, bacteria, protozoa, and parasites, only a small number of organisms cause natural infection and only a portion of that group cause clinical disease. The efficacy of canine, porcine, human, and autogenous Bordetella vaccines and bacterins has been evaluated by several individuals; reports suggest that these vaccines do not completely protect guinea pigs from infection, but a decrease in the incidence and severity of clinical disease has been noted in experimentally challenged animals (Matherne et al., 1987; Stephenson et al., 1989) .
cord-283779-mudwcypl	2020	The chronic increase in inflammatory cytokines, augmented by COVID-19 infection, may explain the higher tendency for "the cascade leading to pulmonary fibrosis and insufficiency and activation of clotting" and poorer clinical prognosis, especially in multimorbid older persons (4) . In case of persistent fever, higher than 37.5°C for a time longer than 3 days and peripheral oxygen level lower than 95% after starting therapy, we should consider and proceed to hospitalization especially in multimorbid older patients with cardiac, respiratory diseases and diabetes. First, patients at risk for poor outcomes and higher mortality following infection with SARS-CoV-2, namely older adults and multimorbid individuals, should be checked for malnutrition through screening and assessment. Older patients infected by COVID-19 often experience atypical and less severe symptoms in older persons, side-effects of the drugs and require specific nutritional and motor treatment for avoiding disability and death.
cord-287607-d3k26aar	2020	Ongoing ''Stay at Home'' orders and institutional policies mandating ''Work from Home'' for non-essential employees, which includes most research personnel, have impacted the ability to implement and conduct clinical studies. At the same time, plans were implemented to continue collection of data to achieve endpoints, safely enroll and follow participants in studies offering potential benefit, and quickly implement new COVID-19 clinical trials. These efforts were directed at the identification of the following areas that would require modification: minimization of direct patient care for routine study activities, logistics of research staff working from home, and study-specific protocol deviations, enrollment pauses, and remote site monitoring visits (Figure 3) . Sponsors were highly responsive, providing amendments to allow for study adjustments, including suspension of enrollment when appropriate for a specific study, protocol modifications to allow for remote follow up and designed for participant safety as well as to assure that data collection to achieve endpoints could be collected, and implementation of remote monitoring, etc.
cord-289520-i6pv90s9	2020	RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. Outbreaks, especially of novel agents, create a pressing need to collect data on clinical characterization, treatment, and validation of new diagnostics to inform rapid public health response. We compared our findings to the 2018 systematic review on SARS and MERS to determine which questions have already been addressed, what information is lacking, and provide recommendations for data sharing and clinical study designs to be conducted during the current outbreak. These observational studies are practical in the fast-paced outbreak setting, as they are easier than randomised controlled The First Few X (FFX) WHO Protocol https://www.who.int/publications-detail/the-first-few-x-(ffx)-cases-and-contact-investigation-protocol-for-2019-novel-coronavirus-(2019-ncov)-infection) What are the risk factors for death or severe illness?
cord-293151-g3758oes	2015	This provides the necessary background to discuss the spontaneous diseases, including infectious and neoplastic conditions, prevalent in purpose bred as well as random source dogs used in biomedical research. Several factors that increase pressure at the site and/or affect the integrity of the skin will predispose an individual to develop pressure sores, including poor hygiene, self-trauma, low-protein diet, preexisting tissue damage, muscle wasting, inadequate bedding, and ill-fitting coaptation devices (Swaim and Angarano, 1990) . Chronic or recurrent corneal ulcers may also be associated with infection or hereditary causes in some breeds of dogs; however, these would be rare in the laboratory setting. Research Complications Treatment of early-stage or low-grade mammary tumors may be rewarding, allowing dogs to continue on study.
cord-296692-t5p09le8	2020	In December of 2019 cases of an unknown viral pneumonia were reported from Wuhan, Hubei, China Although much uncertainty remains, regarding the natural history and demographics of COVID19 , the virus appears to primarily cause infection in adults over 51 with case fatality rates increasing dramatically with age [5] . There are, however, emerging case reports of pregnant mothers who test positive for COVID-19 infection and who remain either completely asymptomatic [23] and or manifest mild symptoms in the subsequent 24 hours following delivery. Although clinical evidence is lacking, the case numbers to date of COVID-19 in pregnancy remain very low [32] and case reports of two neonates who tested positive for SARS-CoV-2 shortly after birth lends some credence to the concern. Vertical transmission of coronavirus disease 19 (COVID-19) from infected pregnant mothers to neonates: A review An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: Maternal coronavirus infections and pregnancy outcomes
cord-298899-lkrmg5qr	2020	To fill the research gaps mentioned above, this review article systematically summarizes global findings on the natural history, clinical spectrum, transmission patterns, laboratory findings, CT results, and risk factors of the COVID-19. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical course and potential predicting factors of pneumonia of adult patients with coronavirus disease 2019 (COVID-19): a retrospective observational analysis of 193 confirmed cases in Thailand Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan Epidemiology, risk factors and clinical course of SARS-CoV-2 infected patients in a Swiss university hospital: an observational retrospective study
cord-299082-s8bm40vy	2020	5, 6, 9, 10, [12] [13] [14] [15] Several investigators have reported cardiac function and structural abnormalities in patients with SARS-CoV-2 infection, including acute heart failure (HF), 3,10,16 takotsubo syndrome, 17 ,18 viral myocarditis, 19 and acute myocardial infarction. In addition to exacerbating the previous cardiomyopathy and conduction disorders, inducing arrhythmia events, SARS-CoV-2 may also induce electrophysiological abnormalities in patients with no previous history of heart disease under a variety of mechanisms. Clinical features and mechanism of heart injury in patients suffered from severe acute respiratory syndrome. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19)
cord-300325-f3eomugb	2020	Scientific literature and media outlets constantly highlight the work of nurses and doctors on the frontline, but this article will specifically focus on the role of the clinical pharmacist during the coronavirus pandemic emphasizing the extraordinary work done to ensure safe effective therapy was provided to optimize health outcomes in hospitalized patients (5) (6) (7) (8) . In cases where adequate supply could not be obtained in a timely manner, clinical pharmacists used the established communication channels with their clinical teams to implement preemptive shortage management strategies that avoided therapeutic interruptions, optimized patient care, and mitigated stress for other frontline staff. To ensure rapid system-wide implementation of strategies such as the use of alternative analgosedation for an entire unit, clinical pharmacists established direct email communication chains with the Chair of the Medicine and Critical Care departments, who included these recommendations in their daily briefings to hospitalists and advanced practice practitioners in those areas.
cord-304479-uxp1kg86	2020	Finally, recently, a case report study from Japan shows that orally inhaled ciclesonide alleviates the local inflammation in the lung of patients with COVID-19 pneumonia and inhibits the propagation of the virus by antiviral activity [60] . In the same way, a recent case-report study showed that the adoptive transfer therapy of human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) to a Chinese female patient afflicted with acute COVID19 syndromes improved her laboratory tests and CT images [69] . In vitro evidence of activity against SARS-CoV-2 in infected Vero E6 cells reported with high concentrations of the drug [104, 105, 142] FPV significantly improved the latency to relief for pyrexia and cough [99] FPV in patients with COVID-19 led to decrease of viral load and significant improvement in chest imaging compared with the control arm [98] 
cord-306351-ka6asw3m	2020	Several trials of Remdesivir treatment on few patients in the United States have shown early promising benefits in cases with severe pneumonia [33, 34] . On the other hand, data emerging from other ongoing Chinese trials have demonstrated that CQ phosphate is superior to a control treatment in the following areas: pneumonia exacerbation inhibition, imaging findings improvement, virus negative conversion promoting, and disease course shortening [62] . For example, clinical data from reliable randomized controlled studies are still missing, and data published to date lacks homogeneity in terms of recommended dose concentration, treatment duration, and severity of patient illness [58] . Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China
cord-308284-r546ypur	2020	Several potential regulatory scenarios may exist and co-exist during an epidemic: for example, (a) de-novo candidates requiring rapid development and regulatory assessment (b) de-novo products requiring assessment when the typical package of clinical efficacy data may not be available, (c) approval of de novo or repurposed products for "emergency" use only in specific populations (d) for compassionate use in specific (e.g., "named") individuals of an unauthorized medicine (e) conditional or accelerated authorization before the completion of efficacy studies or, (f) use of a licensed product outside of its approved use (e.g., for another indication, dosage regimen, or population). Conditional term-limited approval 22 FDA''s Expanded Access (EA) is a program designed for patients with an immediately life-threatening disease to access a product that has clinical trial data (putatively showing an acceptable benefit-risk profile)-but does not yet have marketing authorization.
cord-308421-22rcptor	2020	ECRO will aim to provide the views of ESMO on clinical research procedures based on the feedback from clinical investigators, under complete adherence to the Declaration of Helsinki, the GCP guidelines and any other applicable legal regulations, while at the same time showing profound respect for all the stakeholders involved in clinical research. ECRO will aim to provide the views of ESMO on clinical research procedures based on the feedback from clinical investigators, under complete adherence to the Declaration of Helsinki, the GCP guidelines and any other applicable legal regulations, while at the same time showing profound respect for all the stakeholders involved in clinical research. While adherence to the Declaration of Helsinki, GCP guidelines and local regulations remains unquestionable, many experienced investigators believe that their overinterpretation and misinterpretation by Clinical Research Organisations (CROs), and their substitution by their own internal Standard Operating Procedures have significantly increased the administrative burden.
cord-309080-1r8t8yxv	2020	Like nursing, midwifery and many allied health education programmes, clinical training is an important cornerstone of radiographer education -equipping students to safely and competently transit into complex healthcare environments 6, 7 . However, as all the overseas students were selffinanced, the potential of additional emotional and psychological challenges had to be considered 12 One of the ways of support for the clinical educators came in the form of encouragement from notes of appreciation and gifts from the public, and the hospital senior managements to all frontline heroes -showing how much their efforts were valued through these gestures of care and appreciation. Indeed, these characteristics of Generation Z students will certainly affect how clinical educators provide education in the COVID-19 pandemic. With the new ratio, clinical educators were able to provide the students with more guidance, frequent immediate feedback and encouragement to learn from their mistakes -meeting the Generation Z students'' learner perspectives [36] [37] .
cord-310027-846vp7ii	2020	METHODS: We did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process. We extracted the following information from registered studies: registration number, registration date, registration title, primary sponsor, funding source, study type, study phase, study objectives, study design, length of the study, intervention, countries of recruitment and research settings, recruiting status, allocation, sample size, participant age, gender, masking, the time and method of sharing individual participant data (IPD), data management committee. Among the 943 interventional studies, 416 studies (44.1%) explored the effectiveness and/or safety of drugs commonly used in preventing and treating COVID-19, such as hydroxychloroquine (HCQ), chloroquine (CQ), immunotherapy (including stem cell therapy, monoclonal antibody, immunoregulation), lopinavir/ritonavir, glucocorticoids, interferon, targeted therapy (Baricitinib, Ruxolitinib, Imatinib), favipiravir, and Remdesivir.
cord-310150-j1mvr9r9	2020	title: Identification of common and severe COVID-19: the value of CT texture analysis and correlation with clinical characteristics These features were then used to construct a radiomics texture model to discriminate the severe patients using multivariate logistic regression method. (4) The Spearman correlation analysis showed that most textural and clinical features had above-moderate correlations with disease severity (> 0.4). Both the clinical model and radiomics signature showed good performance in discriminating patients with common and severe COVID-19. Both the clinical and radiomics models showed good stability, indicating that the texture analysis was valuable for discriminating common and severe COVID-19 patients, and that the results were not due to overfitting. The strong correlation was found between inflammatory score and partial wavelet transform features and region size matrix GLSZM features (> 0.7), indicating that these image features are closely related to disease severity and can be used for clinical type classification of the COVID-19 patients.
cord-310205-j57x9ke6	2007	A major task of the primary care physician is to identify those patients with acute pharyngitis who require specific antimicrobial therapy and to avoid unnecessary and potentially deleterious treatment in the great majority who suffer from a benign, self-limited, usually viral infection. In the minority of patients who are severely ill or toxic at presentation and in whom clinical and epidemiologic evidence leads to a high index of suspicion, oral antimicrobial therapy may be initiated while awaiting the results of the throat culture. Treatment of GAS pharyngitis is recommended to prevent acute rheumatic fever, prevent suppurative complications [28] , shorten the clinical course (although only modestly) [28] , and reduce transmission of the infection in family and school units. Within days to weeks after initial infection with HIV type 1, 50% to 90% of patients develop a constellation of symptoms known as the ''''acute retroviral syndrome.'''' Fever, sore throat, lymphadenopathy, maculopapular rash, myalgia, arthralgias, and mucocutaneous ulcerations are the landmarks of the syndrome [58] [59] [60] [61] .
cord-311806-3zy5kgo5	2020	One crucial role of a physician who is an expert on rare disorders is to recognize the cardinal features related to the syndrome and to be aware of potential complications in order to plan a personalized care plan so as to monitor signs and symptoms, prevent secondary complications, and support interconnections with local healthcare providers. This section refers to how lack of experience about clinical management of specific genetic conditions may affect patient''s outcome even Angelo Selicorni and Giuseppe Zampino contributed equally to this study. Valentina Giorgio acquired clinical data on Case 1 (first patient), reviewed, and revised the manuscript. Mauro Celli acquired clinical data on Case 2, reviewed, and revised the manuscript. Angelo Selicorni acquired clinical data on Case 1 (second patient), reviewed, and revised the manuscript.
cord-312677-rwznqiib	2020	Sixty-six publications and 111 clinical trials were recognized as eligible, reporting the efficacy of the immunomodulatory agents, including corticosteroids, hydroxychloroquine, passive and cytokine-targeted therapies, mesenchymal stem cells, and blood-purification therapy, in COVID-19 patients. Various studies have focused on the efficacy of the immunomodulatory agents including corticosteroids, hydroxychloroquine or chloroquine, cytokine-targeted therapies (e.g., anakinra, siltuximab, or tocilizumab), passive immunotherapy (convalescent plasma and intravenous immunoglobulin), mesenchymal stem cells, and bloodpurification therapy, mostly as adjuvant therapy for treatment of the patients with severe COVID-19 and partly have reported promising outcomes. Included clinical studies with 1-63 participants have shown that both antagonists, specially TCZ, are effective in reducing the mortality rate specially in the severely ill patients, improving the symptoms including fever resolution, oxygenation and resolved CT scans, reducing the inflammation markers (ferritin, CRP, and D-dimer), weaning from the ICU hospitalization and ventilation, and dampening the risk of disease progression to ARDS by mitigating the cytokine storm in the NCP patients [60, 62] , as applied for CRS controlling in the CAR-T therapy [90] .
cord-315598-qwh72inx	2020	De otorgarse un Consentimiento Informado amplio, éste debería ser única y exclusivamente para los procesos asociados con COVID-19".(71) AMCI ® Se recomienda considerar la transición del cuidado intensivo al cuidado paliativo en todo paciente con sospecha o diagnóstico de COVID-19 sin mejoría a pesar de las intervenciones óptimas, con empeoramiento progresivo de su pronóstico vital y ante un evidente deterioro; aplicando medidas generales en control de síntomas ( Manejo de secreciones -Tratamiento del dolor -Tratamiento de la disnea -Sedación paliativa), así como apoyo espiritual, siempre acompañando al paciente y nunca abandonarlo en el final de la vida. En cuanto hace referencia a la situación actual de pandemia por SARS-CoV-2 y compromiso pulmonar; Wu y cols, en Marzo de 2.020 realizaron un estudio retrospectivo de 201 pacientes con COVID-19 en China; para aquellos pacientes que desarrollaron SDRA, el tratamiento con metilprednisolona estuvo asociado con una disminución del riesgo de muerte (23/50 [46%] con esteroides vs 21/34 [62%] sin esteroides; HR, 0.38 [IC 95%, 0.20-0.72]), con las limitaciones de los estudios retrospectivo, de un solo centro, con un limitado número de pacientes (400).
cord-315730-fzgxuak7	2020	Owing to their efficacy against viruses (mostly demonstrated in vitro) including influenza, HIV, coronavirus OC43, and SARS-CoV, a large number of clinical trials (>230) have been registered worldwide using chloroquine/hydroxychloroquine alone, or in combination with other drugs (e.g. azithromycin) for the treatment of COVID-19. At the time of writing, the RECOVERY trial (clinical trial identifier NCT04381936) which is the largest randomised control trial so far conducted for the treatment of COVID, has stopped recruiting to the hydroxychloroquine arm (1542 patients compared with 3132 on standard care) because of no beneficial effect either in terms of mortality or hospital stay (P. Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial
cord-316029-z708c3ex	2020	This review will offer key clinical pharmacology considerations for developing small molecules for the treatment of COVID-19 based on the major disease complications that impact drug absorption, distribution, metabolism, and elimination (ADME). Of major concern is sepsis, defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." 12 In 1 study, septic shock, which is distinguished by persistent hypotension, elevated serum lactate levels, and increased mortality, was a complication in about 6% of severely ill COVID-19 patients. For water-soluble investigational therapies that are intended for administration in the severely ill COVID-19 population, thought should be given to targeting serum drug concentrations and the drug''s exposure-response profile when determining if increased doses would be beneficial for patients receiving intravenous fluids. 21 The clinical impact of these potential changes in free drug fractions on investigational therapies that are highly proteinbound is an important consideration when empirically selecting doses for critically ill COVID-19 patients.
cord-316432-xemz7zn9	2020	METHODS: Pubmed, Embase, Scopus, Cochrane, and Scholar databases were searched from inception to July 1, 2020, to identify studies reporting the current treatment process and medications (e.g. hydroxychloroquine, antiviral therapy, convalescent plasma, and immunomodulatory agents) for COVID-19. Zhong et al., provided a systematic review and meta-analysis including the therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) mainly besides COVID-19 and assessed their safety and efficacy profiles [31] . All types of studies i.e. randomized controlled trials (RCTs), prospective or retrospective cohort studies, and the case series that investigated clinical outcomes and/or viral clearance among adult patients were included to conduct this study. In agreement with previous researches, our meta-analysis results showed that the administration of immunomodulatory agents (especially tocilizumab and anakinra) significantly decreased the mortality rate and ameliorate clinical symptoms in patients with COVID-19 [113, 114] . Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis
cord-316647-jj8anf5g	2020	RESULTS: A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Statement 8 Convalescent plasma therapy should probably be used for severe and critically ill patients with COVID-19 (Grade 2+, weak recommendation). However, critically ill patients with COVID-19 have a longer mechanical ventilation time, and daily sedatives interruption is not suggested for patients receiving deep sedation in order to reduce lung damage during early stage of severe ARDS. Light sedation is suggested for severe COVID-19 patients receiving HFNC oxygen therapy and non-invasive mechanical ventilation, and also for critically ill patients in the recovering stage (expert opinion). Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial
cord-316886-qzka2dqm	2020	This paper provides a series of reflections of an academic socio-ethicist''s (LM) and a senior clinician''s (MW) experiences of making the case for the introduction of Clinical Ethics Support Services (CESS) within a National Health Service (NHS) Trust. The paper will outline the journey of the academic being approached by the clinician to consider setting up a CESS at the Trust, to being faced with the daunting task of completing a business case, to working collaboratively with clinical colleagues to prepare a proposal to the Trust Executive Board. The literature confirmed that healthcare staff need reflective spaces within institutions in which to explore and communicate values and ethical obligations as they undergird goals of patient care (Hamric and Wocial 2016) and the CESS could play a role in creating and designing these spaces, and ensuring they remain "open, accessible and active" (Walker 1993, p.
cord-317952-4oa9hfb4	2020	ACE2 was highly expressed on lung alveolar epithelial cells and small intestinal epithelial cells, consistent with potential routes of viral transmission of SARS-CoV-2, as both respiratory and gastrointestinal systems share interfaces with the external environment. ACE2 expression in the lungs and SARS-CoV-2 viral load have been suggested to increase with age, which might provide an explanation to the higher disease severity observed in older patients with COVID-19 [35] . Both SARS-CoV-2 infection, directly mediated by ACE2 expression and activity, and superimposed disease triggers may be responsible for the observed pathological findings. Additionally, another study reported purpura and livedo racemosa in several severely affected COVID-19 patients with small vessel thrombosis with co-localization of complement and SARS-CoV-2 spike proteins on histopathology [148] .This indicates direct viral infection of the small skin vessels. Circulating plasma concentrations of ACE2 in men and women with heart failure and effects of renin-angiotensin-aldosterone-inhibitors: Potential implications for coronavirus SARS-CoV-2 infected patients
cord-318209-llucxztc	2020	A phase-1 clinical trial investigating autologous BM-derived mononuclear cell (BM-MNC) infusion in pediatric TBI patients indicated that Fig. 1 Main pathological conditions requiring acute emergency care that can benefit from stem cell therapies or extracellular vesicle therapies in the future harvesting and infusion of stem cells is safe in children with no infusion related toxicity or death [30] . The regenerative potential of various types of stem cells, with different sources, dosages, delivery routes, application times and end-points has been investigated in preclinical animal models and human clinical trials with the expectation that these cells would successfully engraft into the damaged brain tissue, differentiate into functional neuronal and vascular system cells and promote full recovery after stroke. A recently published systematic review of 76 studies testing stem cells in rodent ischemic stroke models and 4 randomized human clinical trials encompassing ischemic stroke patients treated with autologous stem cells with at least one year follow-up period demonstrated that stem cell therapies show beneficial effects in terms of behavior and histological outcomes in rodents.
cord-319805-b6ypt5d0	2020	We systematically searched electronic databases including MEDLINE (accessed by PubMed), EMBASE and Cochrane Library for identification of all available observational studies that reported on laboratory-confirmed COVID-19 patients aged ≥18 years with information given on disease severity and past history of CVD. Multivariable logistic regression was performed to explore the predictive value of history of CVD for severity outcomes of COVID-19 including clinical severity according to the classification by the National Health Commission guidelines on the Diagnosis and Treatment of COVID-19, in-hospital death and necessity of intensive care [10]. When considering only published data from Chinese cohorts in pooled analysis (n = 1805), history of CVD was also associated with increased risk of severity of COVID-19 (RR 2.39, 95% CI 1.94-2.94; p < 0.0001) with similar results on sensitivity analyses for study-specific severity outcomes (clinical parameters: RR 1.83, 95% CI 1.28-2.63; p = 0.001; necessity of intensive care: RR 2.9, 95% CI 1.61-5.24; p < 0.0001 and in-hospital death: RR 2.14, 95% CI 1.7-2.7; p < 0.0001).
cord-319933-yp9ofhi8	2013	An experimental study with cell culture-adapted hepatitis Avirus in guinea pigs challenged by oral or intraperitoneal routes did not result in clinical disease, increase in liver enzymes, or seroconversion. 32 NHPs including marmosets, cotton-top tamarins, and rhesus macaques infected with Norwalk virus can be monitored for the extent of viral shedding; however, no clinical disease is observed in these models. 66, 67 Intracerebral and intranasal routes of infection resulted in a fatal disease that was highly dependent on dose, while intradermal and subcutaneous inoculations caused only 50% fatality in mice regardless of the amount of virus. A mouse-adapted (MA) strain of Dengue virus 2 introduced into AG129 mice developed vascular leak syndrome similar to the severe disease seen in humans. [138] [139] [140] [141] [142] [143] [144] Inoculation of WNV into NHPs intracerebrally resulted in the development of either encephalitis, febrile disease, or an asymptomatic infection, depending on the virus strain and dose.
cord-323940-ubazgvov	2020	Recently, pharmacogenomics (the effects of a single genetic marker) and pharmacogenetics (the collective influence of variability across the genome to modulate an individual''s drug response) have received great attention for their abilities to provide a new way to select drugs for personalized therapy (optimal dosing for maximizing drug efficacy or minimizing the risk of toxicity). 35 Search terms were "Covid-19", "novel coronavirus", "SARS-CoV2", "pharmacogenetics", "treatment/s", "adverse side effects", "therapy", "lung", "ocular", "pulmonary infection", "drugs", "drug response", "virus", "candidate drugs", "potential inhibitors", "protease inhibitors", "personalized medicine", "individual therapy", "pneumonia", "ACE", "heparin", "vasculitis", "conjunctivitis", "rhinitis", "hematological complication" and "main metabolic routes", either alone or in combination. Drugs in use as routine therapy or in clinical trials for Covid-19 include steroids and antiviral and biological humanized neutralizing antibodies against some proinflammatory cytokines, such as IL1, IL6, IFN, and TNFα, in addition to supportive measures and symptomatic treatment, according to the severity of the disease.
cord-324388-onc441uw	2020	Notwithstanding the low-risk nature of participation in most regional anesthesia clinical trials, subject recruitment on the same day as surgery is often prohibited by local research ethics boards (REB) due to their concerns regarding patient autonomy and perceptions of patient vulnerability immediately before surgery that could impact the voluntary nature and the rigor of the informed consent process.
cord-324607-rpwccvqi	2020	Among the noteworthy successes of vaccine trials, and the commendable efforts to implement clinical treatment trials during Ebola outbreaks, we should also focus on strengthening the collection and curation of epidemiological and observational data that can improve the conception and design of clinical research. Table 1 identifies some key domains that could contribute to a core minimal dataset that informs clinical trial design for each priority pathogen. While these data have their most important benefits in improving patient management (through better recognition of disease complications and informing supportive care) and public health control, patient-based data are also used to determine key parameters for clinical trials, such as the inclusion criteria, the nature and rate of clinically relevant outcomes, and potential confounders. A systematic review and meta-analysis of patient data from the west Africa (2013-16) Ebola virus disease epidemic
cord-325559-di8lljoi	2020	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced disease (COVID-19) is a planetary emergency that is urging many research groups to redirect their efforts and to channel their experience towards understanding its pathogenesis. These human epitopes, in turn, can be recognized by circulating antibodies made against crossreactive microbial antigens; these antibodies behave like autoantibodies, causing the destruction of the stressed cells, representing a typical example of pathology caused by molecular mimicry and manifested as autoimmunity [30] . We hypothesize that, at the basis of the generalized activation of the immune system, there are molecular mimicry phenomena: the antibodies produced against the virus could turn into autoantibodies against crossreactive proteins expressed on human cells, causing autoimmunity with cell destruction. We hypothesize that, at the basis of the generalized activation of the immune system, there are molecular mimicry phenomena: the antibodies produced against the virus could turn into autoantibodies against crossreactive proteins expressed on human cells, causing autoimmunity with cell destruction.
cord-326331-g4o3forj	2020	METHODS: A survey-based study focused on randomized controlled trials (RCTs) and single-arm studies for acute ischemic stroke and cerebral aneurysms was developed by a group of senior neurointerventionalists and sent to sites identified through the clinical trials website (https://clinicaltrials.gov/), study sponsors, and physician investigators. The Food and Drug Administration (FDA) published its guidance on the ''Conduct Of Clinical Trials Of Medical Products During COVID19 Pandemic'' for the industry, investigators, and institutional review boards in March 2020 and updated these on April 2, 2020 (https://www. These were identified by the writing group and fell into four categories: general disruption caused by trial suspensions and missed opportunities of enrollment, compromised trial quality due to inability of timely clinical and imaging follow-up, inability to enroll neurologically debilitated patients because legally authorized representatives were not at hand for face to face consent and dated remote consent procedures did not apply and, finally, personal effect of compensation or working conditions on study staff.
cord-327738-i400ynjp	2020	We discuss here the ethics of clinical trial care within the surgical specialties and the the pros and cons of participation in clinical trial during the COVID-19 pandemic, with a specific focus on surgical oncology and vascular surgery. The current need for social distancing and limitations of health care resources has shifted priorities appropriately, but completely halting clinical trials would hinder dramatically the delopment of novel treatment sand leave patients currently enrolled in these trials without access to potentially life-saving medications. Before continuing to enroll patients in surgical trials, we believe that surgeons must carefully consider the type of trial, the institutional status with respect to scarce resources, and the potential risk/benefit ratio to patients and health care workers involved. Medically-necessary, time-sensitive procedures: A scoring system to ethically and efficiently manage resource scarcity and provider risk during the COVID-19 pandemic
cord-331268-kzy33hdb	1996	Abnormalities in the cerebral hemispheres are frequently periventricular in distribution and only occasionally correlate with specific symptoms or signs.6,7 The accumulation of lesions in the frontal lobes is associated with a decline in memory.8 In addition, a change in the number of lesions on cranial MR images correlates with a change in overall clinical status as measured with standard scales.g Observations made with MRI are having a marked impact on both our basic knowledge of MS and on therapeutic trialsJo MRI studies will provide considerable insight into the natural history of the disease and will be an excellent independent variable in future clinical trials. Signs and symptoms that commonly occur as MS progresses include vertigo, tremor, incoordination, increasing spasticity, depression, mood swings, cognitive abnormalities, impotence or other sexual dysfunction, weakness, Lhermitte''s sign, gait abnormalities, constipation, urinary incontinence, optic nerve pallor, fatigue, quadriparesis, dysarthria, loss of upper extremity coordination, and dysesthetic pain (Table 1) .
cord-331557-8axi74nn	2004	When PCR is used to detect DNA in clinical specimens, microarrays can then be used to identify the amplified products by hybridization to an array that is composed of pathogen-specific probes. Kits are available for the detection and quantification of DNA and RNA in clinical samples, and the technique has been specifically developed to enable the follow-up of patients with HIV and hepatitis C infections (Amplitech AME Bioscience; Bayer Diagnostics; Roche Diagnostics). Mass-spectrometry analysis of base-specific fragmentation patterns of PCRamplified DNA has recently been studied as a technique for the rapid identification of bacterial isolates and for the detection of specific 16S rRNA gene fragments that are amplified from complex environmental samples 35 . These automated microarrays will be suitable both for mass screening of sera in epidemiology studies and in blood banks, and for diagnostics that are carried out on single serum samples in clinical microbiology laboratories.
cord-332078-vl309ss7	2020	Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-19) in a Fangcang Hospital Analysis of epidemiological and clinical features in older patients with Corona Virus Disease 2019 (COVID-19) out of Wuhan A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China
cord-333285-0s6dnm9i	2020	title: Navigating Nonessential Research Trials During COVID19: The Push We Needed For Using Digital Technology To Increase Access For Rural Participants? 1, 2 Thus, despite increased need for effective disease management and health promotion strategies, rural residents are frequently underrepresented in these clinical trials. 3 Second, some rural areas experience systemic barriers to remote clinical trial implementation, such as limited access to Internetenabled mobile devices and requisite bandwidth capacity. When nonessential research activities restart, investigators need to carefully reconsider simply returning to the status quo of solely traditional in-person approaches and develop strategies for implementing protocols, including sample collection, remotely. For example, universities could collaborate with satellite Internet cooperatives to increase access to rural broadband that would support a wide range of public health and clinical care initiatives beyond clinical trial research that would benefit rural areas. Recruitment and participation in clinical trials: socio-demographic, rural/urban, and health care access predictors.
cord-333340-ekok0mp5	2020	PURPOSE OF REVIEW: Major technologic advances in two main areas of molecular infectious disease diagnostics have resulted in accelerated adoption or ordering, outpacing implementation, and clinical utility studies. More studies are needed to assess their prospective impacts on patient management and antimicrobial stewardship efforts as the future state of infectious disease diagnostics will see continued expansion of these technologic advances. This review will highlight recent studies developing and applying emerging molecular infectious disease technologies and touch on limited published data on clinical utility and stewardship approaches. Ideally, we would evaluate all of these approaches via randomized controlled trials comparing patient outcomes between conventional microbiologic testing and testing including a syndromic panel; however, very limited studies addressing this have been published [8] . One of the only randomized controlled trials also found no difference in antibiotic usage, including duration, between adults tested via syndromic panel at the point-of-care compared to patients receiving conventional testing in a hospital emergency department and inpatient unit [15] .
cord-333581-icp0xwhx	2020	Articles were selected if they reported data on COVID-19 patients with respect to gastrointestinal symptoms (diarrhea, abdominal pain, and nausea/vomiting) or laboratory findings (serum AST, ALT, or TB). Our meta-analysis demonstrated significant correlations between gastrointestinal parameters (diarrhea, elevated serum ALT, AST and TB) and severe disease outcomes, i.e., respiratory distress, ICU admission, and/or death. • We performed a comprehensive systematic review and meta-analysis of the available literature through May 31 st , 2020 to assess these manifestations with respect to disease severity • Our results indicate that diarrhea, abnormal ALT, AST and TB were associated with severe disease (intensive care unit admission, respiratory distress, and/or mortality) • Based on the current study results, patients with these manifestations should be stratified as highrisk and managed appropriately Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series
cord-334433-oudvxb4d	2020	Responses to mitigate the effects of the pandemichave included: 1) thedevelopment of strategies to support research programs during unforeseen economic loss, 2)establishment of institutionalguidelines for clinical trials, 3)measures to ensure a healthy clinical research team, 4) useof innovative technologies to maintain access to clinical trials, 5) amendment of protocols to avoid costly trial closures, and 6) the strategic reopening of suspended clinical trials. Efforts to modify protocols in order to comply with the emergency public health response and the guidelines established by the FDA and IRBareencouraged.Investigators need to prioritize collection of data, focusing on the primary endpoint and important secondary endpoints to remain in compliance.Clinical protocols should be reexamined thoroughly and amendments should be made to reduce superfluous clinical visits.While many protocol changes typically required an amendment and lengthy review process, to avoid costly delays, reviews of amendments at our institution are being waived or expedited if the adjustment pertains to patient safety in the setting of COVID-19.
cord-334773-yw2qgv13	2020	This concern has been further confirmed by the results of a cohort study among 85 fatal cases of COVID-19 in Wuhan, hence defining DM as a potentially harmful comorbidity predisposing to worse clinical course or death once SARS-CoV-2 infection occurred [49] . Different hypothesis should be considered for explaining this clinical phenomenon, including glucose control at baseline and during the infection course, pathophysiology and immune system response in SARS-CoV-2 infected patients with T2D, diabetes-related comorbidities and concomitant medications. In conclusion, diabetic patients especially elderly individuals and those with worse baseline glucose control may exhibit immune system dysregulation that predispose them to a less effective response against SARS-CoV-2 and to a dysfunctional inflammation that requires to be carefully monitored in confirmed cases of COVID-19, for preventing or avoiding a harmful progression of the disease. Immune response and systemic inflammation play a crucial role in SARS-CoV-2 infection, particularly in case of severe clinical course of the disease.
cord-336554-n8n5ii5k	2020	Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. Outbreaks of novel emerging infections such as coronavirus disease 2019 (COVID19) have unique challenges in front of the health professionals to select appropriate therapeutics/pharmacological treatments in the clinical setup with very little time available for the new drug discovery [3] . Currently, with the lack of effective agents against SARS-CoV2 as well as public-health emergency, WHO has identified some therapies which doctors and researchers believe are the most promising, such as a combination of two HIV drugs (lopinavir and ritonavir), anti-malarial drugs (chloroquine and hydroxychloroquine), and an experimental antiviral compound remdesivir. Ribavirin at a dose rate of 500 mg 2-3 times/day in combination with other drugs such as lopinavir/ritonavir or interferon (IFN)-α through intravenous route for not more than 10 days made the SARS-CoV2 infected patients more resistant to respiratory distress syndrome as well as death [41] .
cord-336563-hwemigk7	2020	Given the rapidity of emerging literature, IDSA identified the need to develop living, frequently updated evidence-based guidelines to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19. Two RCTs of patients with confirmed COVID-19 with mild pneumonia (e.g., positive CT scan without oxygen requirement) or non-severe infection admitted to the hospital treated with hydroxychloroquine (HCQ) reported on mortality at 14 days, clinical progression (radiological progression on CT scan), clinical improvement, failure of virologic clearance (PCR), and adverse events (both) [11, 12] (Table 1 ). In addition, we identified four publications describing three trials of combination treatment with HCQ plus azithromycin (AZ) among hospitalized patients with COVID-19 reporting on the outcomes of mortality, failure of virologic clearance (assessed with PCR test), and adverse events (i.e., significant QT prolongation leading to treatment discontinuation) [13] [14] [15] [16] (Table 2) .
cord-340028-6oicmeam	2020	Here we compare the expected benefit of treatments for elderly populations (60 years and older) that are currently in development, including standard preventative strategies such as vaccines and antivirals targeting SARS-CoV-2, and the potential added benefit of speculative geroprotective strategies such as rapalogs, NAD+ boosters, senolytics, and stem cell treatment. People >60 years of age with chronic medical conditions, such as type 2 diabetes or cardiovascular disease, direct immunosuppression from HIV, posttransplant or biologic treatment, pregnant individuals, or those with BMI>40, are believed to be at higher risk for influenza infection due to a weakened immune response [31] . As discussed in this paper, small clinical studies have shown that several geroprotective and senoremediative interventions, such as treatment with AGING sirolimus and rapalogs, can induce immunopotentiation, increase resistance to infection, and reduce disease severity in the elderly, without severe side effects.
cord-340415-6fte7krp	2020	In the face of high health care demand during the peak of a pandemic, safe management of low risk patients in the community will likely be essential to preserve hospital capacity for the more severely ill. This position is endorsed by the Australasian Society for Infectious Diseases interim guidelines for the clinical management of COVID-19 in adults, 20 guidelines for the clinical care of people with COVID-19, 19 which state that even where conditional recommendations for use of disease modifying agents are made, whenever possible these should be administered in the context of randomised trials with appropriate ethical approval. 37, 38 However, given the current lack of evidence of clinical benefit and reports of significant limitations of supply of hydroxychloroquine for patients with rheumatological conditions, in March 2020, the Pharmaceutical Society of Australia and the Australasian Society for Infectious Diseases called for immediate cessation of prescribing and dispensing of hydroxychloroquine for indications relating to COVID-19, outside use in approved clinical trials. Specific antiviral therapy in the clinical management of acute respiratory infection with SARS-CoV-2 (COVID-19).
cord-340656-ltd6ueoi	2020	title: The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries Furthermore, with few included studies (30 in the largest and most recent [12] ), the range of symptoms were limited and the estimates of prevalence are likely to be upwardly biased because only unwell patients (largely those admitted to hospital) were tested in the early phase of the outbreak. We excluded case reports, articles which failed to disaggregate symptoms in adult and paediatric cohorts, studies of patients with prior respiratory infections (e.g. tuberculosis) or co-infections with other viruses (e.g. similar viruses SARS-CoV-1 or HCoV-EMC/2012, etc) and articles which we are unable to translate to English in a timely fashion. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms
cord-341801-n11ilz6l	2020	title: Wearable technology and live video conferencing: The development of an affordable virtual teaching platform to enhance clinical skills education during the COVID-19 pandemic As a result, the University of Toronto''s medical school has pivoted to teaching clinical skills using online modules and pre-recorded e122 videos of physicians taking patient histories and performing physical examinations. In this commentary, we identify an affordable and user-friendly device-accessory pairing compatible with live VC technology that can be adapted for use throughout medical or other healthcare education programs. Tutors who already own smartphones can easily couple them with institution-provided chest straps and Zoom © accounts to resume group teaching of clinical skills. We have demonstrated that the use of a chestmounted smartphone with Zoom © VC technology is an interactive, accessible, cost-effective, and feasible e124 adaptation for virtual clinical skills teaching in real time. Limitations in virtual clinical skills education for medical students during COVID-19
cord-342756-rgm9ffpk	2020	Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment.
cord-343715-y594iewi	2020	Patients infected with this new coronavirus present with a variety of symptoms, which range from asymptomatic disease to mild and moderate symptoms (mild pneumonia), severe symptoms (dyspnoea, hypoxia, or > 50% lung involvement on imaging) and symptoms of critical illness (acute respiratory distress syndrome, respiratory failure, shock or multiorgan system dysfunction). A large retrospective observational study from China showed that among 214 hospitalized patients with confirmed SARS-CoV-2 infection, 36.4% had neurological manifestations [114] . The correlation of disease severity with neurological symptoms was confirmed by another retrospective study from France, reporting a prevalence of 84% of neurological manifestations in 58 hospitalized patients with acute respiratory distress syndrome (ARDS) due to COVID-19 [115] . Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series
cord-344705-co0nk7pt	2020	We here discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision‐relevant clinical trials. Many small stand-alone trials and observational studies of single-agent interventions are currently running or in planning; many of these will likely not deliver robust results that could support regulatory and patient-level treatment decisions. We here discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision-relevant clinical trials. Now is the time to ensure that the window of opportunity will not shut, both for patients in need of treatment and for researchers to conduct clinical trials that deliver.
cord-345371-pjbviagq	2020	The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. Here, we review the recently published literature on the pharmacological treatments used so far and/or undergoing evaluation in clinical trials, with focus on the biochemical mechanisms of action of repurposed or investigational drugs, classified as agents directly targeting the virus ( Figure 1 and Table 1 ) and those used to treat the respiratory distress and inflammation associated with the cytokine release syndrome ( Figure 2 and Table 2 ).
cord-346539-kxnrf5g5	2020	This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. The first cases of the coronavirus disease 2019 (COVID19) , caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), were reported in China in December 2019 1 and rapidly led to pandemic. 40, 41 A seroconversion study in COVID-19 patients has found and association between disease severity and SARS-CoV-2-specific IgA levels. Mesenchymal stem cell therapy may potentiate the low IFN-I and -III levels and moderate IFN-stimulated gene response reported in SARS-CoV-2-infected ferrets and COVID-19 patients. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial
cord-347189-i9rzo3j0	2020	The COVID-19 pandemic suggests that it is possible to alleviate redundancy in clinical trials, and while preserving the rigour of a study, can offer a new, less burdened and more inclusive vision of clinical research for the scientific community of tomorrow. Data from China reported that patients with cancer who are infected with COVID-19 are at 3.5 times the risk of requiring mechanical ventilation or intensive care unit (ICU) admission, compared with the general population. 4 Although conversion to telemedicine has maintained the continuity of care for many patients, the COVID-19 pandemic has massively disrupted clinical research and many cancer centres halted clinical trial activities including patient recruitment. COVID-19 has pointed out that sometimes, high level of bureaucracy in research rules place unnecessary burdens on patients and clinicians and it suggests that it is time to alleviate bureaucracy and introduce some practical changes into research organisation that will possibly promote patient access to trials and reduce the costs of the clinical research.
cord-348137-dzmbfp2g	2020	Using data from Shenzhen, China, where all cases were monitored in hospital and symptom profiles and clinical and lab results were available starting from early stages of clinical course, we characterized clinical progression of COVID-19 cases and determined important predictors for faster clinical progression to key clinical events and longer use of medical resources. We estimate time from symptom onset to key clinical events, such as first clinical diagnosis, progression to severe clinical stages, development of acute respiratory distress syndrome (ARDS), admission to the critical care unit (ICU), and discharge. The primary endpoints in this study include patients'' time from symptom onset to clinical progression beyond the moderate stage, ICU admission, invasive ventilator use, and discharge. . https://doi.org/10.1101/2020.04.22.20076190 doi: medRxiv preprint Table 3 : The association of demographic characteristics, baseline comorbidity, initial symptoms, and initial lab results with rate of clinical progression to severe stage, acute respiratory distress syndrome, and ICU admission .
cord-348244-1py0k53e	2020	We describe the principles of central statistical monitoring, provide examples of its use, and argue that it could help drive down the cost of randomized clinical trials, especially investigator-led trials, whilst improving their quality. Yet, there is no evidence showing that extensive data monitoring has any major impact on the quality of clinical-trial data, and none of the randomized studies assessing more intensive versus less intensive monitoring has shown any difference in terms of clinically relevant treatment outcomes [18] [19] [20] [21] [22] . Both types of trials may benefit from central statistical monitoring of the data; industry-sponsored trials to target centers that are detected as having potential data quality issues, which may require an on-site audit, and investigatorled trials as the primary method for checking data quality. An evidence-based study of the cost for data monitoring in clinical trials A statistical approach to central monitoring of data quality in clinical trials
cord-349210-8t4a5qqo	2020	Immunomodulatory biological therapies are being evaluated in clinical trials for the management of the systemic inflammatory response and pulmonary complications in patients with advanced stages of COVID‐19. A randomized, open-label, controlled trial for the efficacy and safety of adalimumab in patients with elevated TNF-α levels in the critical stages of severe COVID-19 is ongoing in Shanghai, China, with the main outcome of time to clinical improvement. A Phase 2 trial of the efficacy and safety of infliximab was initiated to evaluate whether early institution of TNF-α inhibitor therapy in patients with severe COVID-19 infections could prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality at a 5 mg/kg IV single dose. extrinsic factors ( Route of administration: As described before, the immunomodulatory therapeutic proteins currently in clinical trials for the treatment of COVID-19 mostly are directed towards patients with moderate and severe stages of the disease.
cord-350571-6tapkjb6	2017	Possible solutions might be to use shared communication tools like Internet based communication programs and to introduce the patient as a participant at the IMRs. Please specify your abstract type: Research abstract Background and objective: International good pharmacy practice guidelines describe how pharmacists should counsel the patients about their medicines, offer additional services where needed, and intervene at drug related problems. Please specify your abstract type: Descriptive abstract (for projects) Background and objective: In order to improve the medication reconciliation and to implement training programs for the medical team in an associated to general hospital nursing (ASNH) home we measured the discrepancies between pharmacy registered treatments (PRT) and medical prescriptions (MP), and we analysed potentially inappropriate prescriptions according to ''''American Geriatrics Society 2015 Beers Criteria'''' and ''''STOPP-START 2014 criteria.
cord-350793-bftztg0e	2018	Review results show that most published algorithms: (a) are designed for one specific type of CCU; (b) are validated on data harvested only from one Original Equipment Manufacturer (OEM) monitor; (c) generate Signal Quality Indicators (SQI) that are not yet formalised for useful integration in clinical workflows; (d) operate either in standalone mode or coupled with CED or PD applications; (e) are rarely evaluated in real-time; and (f) are not implemented in clinical practice. In conclusion, it is recommended that AD algorithms conform to generic input and output interfaces with commonly defined data: (1) type; (2) frequency; (3) length; and (4) SQIs. This shall promote (a) reusability of algorithms across different CCU domains; (b) evaluation on different OEM monitor data; (c) fair comparison through formalised SQIs; (d) meaningful integration with other AD, CED and PD algorithms; and (e) real-time implementation in clinical workflows.
cord-352177-05sku8a8	2020	To additionally explain patient willingness to participate in new-drug studies or research associated with pharmaceutical companies or with public institutions, further models used the same predictive variables as for the first model, plus distrustgroup-membership as an additional explanatory variable. Our study aimed at evaluating variables associated with patient willingness to participate in different categories of clinical trials and at identifying a potential recruitment bias in clinical trials related to patient distrust in the pharmaceutical industry and healthcare systems. Several studies have previously evaluated such rates and highlighted that altruism, hope for personal benefit, contribution to advances in science as well as financial benefit are the main reasons for agreeing to participate, whereas fear of adverse events, impossibility to cope with the logistic constraints accompanying participation, poor knowledge about or negative perception of clinical trials and distrust in pharmaceutical industry are potential barriers [20] [21] [22] [23] . Distrust in pharmaceutical companies is associated with a specific patient profile and with refusal to participate in pre-marketing industry-sponsored drug trials.
cord-353330-j00jj2og	2004	It may be happenstance that their tenures were contemporaneous with reasonably defined advances and achievements in the field: "Managing Editor" Appleton (1955) (1956) (1957) (1958) (1959) (1960) (1961) (1962) (1963) (1964) (1965) (1966) (1967) (1968) (1969) with the period establishing the discipline as we know it today and with the automation of classical chemistry procedures; "Executive Editor" King (1970 King ( -1990 coincided with advances in immunoassay, computer-assisted techniques, and new instrumentation; and our current adjectiveless "Editor" Bruns (1991-) has been coeval with applications of molecular biology and evidence-based medicine. AACC establishes a bimonthly scientific journal-Clinical Chemistry-"to raise the level at which chemistry is practiced in the clinical laboratory; to stimulate the development of new methods for use in the clinical laboratory; to encourage those engaged in this field to pursue advanced studies so as more effectively to render service to the public; and to create and maintain a forum where clinical chemists may exchange ideas and information concerning their scientific, technical and professional problems." The first volume comprises some 430 pages.
cord-353528-8a3f5hxu	2020	Although the mechanism of action in human patients is not well elucidated, results from pre-clinical studies of Alofisel indicate that induction of indoleamine 2,3-dioxygenase (IDO) in the presence of inflammatory factors such as interferon- (IFN-) is critical for the therapeutic effect of MSCs. This is because the enzymatic activity of IDO can inhibit T cell function and proliferation and increase the number of regulatory T cells, leading to an increase in anti-inflammatory cytokines [e.g., interleukin-10 (IL-10)] and decrease in pro-inflammatory cytokines [e.g., IFN- and tumor necrosis factor- (TNF-)] (14) . (64) reported that MSCs genetically engineered to express thioredoxin-1 (Trx1)-a powerful antioxidant, transcription factor, and growth factor regulator-improved cardiac function following MI in a rat model compared to unmodified MSCs. Although preclinical Priming MSCs with small molecules is a simple and promising approach to induce the secretion of immunomodulatory and regenerative molecules, but the effect of small molecules only lasts a few hours to a few days.
cord-353887-f4yd7guj	2020	Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients. In this review, we referred COVID-19 associated cytokine storm as the patients who are severely ill along with a high concentration of pro-inflammatory cytokines. The innate and adaptive immune responses activated by SARS-CoV-2 infection lead to uncontrolled inflammatory responses and ultimately cause the cytokine storm (14) . MERS-CoV infects the cells mentioned above to induce delayed (but increased) levels of pro-inflammatory cytokines (e.g., IL-2) and chemokines (e.g., CCL2, CCL3) (27, 30) . Although SARS-CoV is abortive in macrophages and DCs, the virus induces an increase in levels of pro-inflammatory cytokines and chemokines (31, 32) . A comment and a meta-analysis, which mainly bases on the evidence of SARS and MERS (64, 65) , stated that corticosteroid would increase mortality and delayed clearance of viral in coronavirus infection diseases.
cord-354216-4khdcjed	2020	Abstract Background Multiple gastrointestinal (GI) symptoms including diarrhea, nausea/vomiting, and abdominal pain, as well liver enzyme abnormalities have been variably reported in patients with COVID-19. The AGA) Institute Clinical Guideline Committee and Clinical Practice Updates Committee performed a systematic review and meta-analysis of international data on GI and liver manifestations of COVID-19. 4 More recent data from a cohort of 5700 hospitalized patients with COVID-19 within a large healthcare system in New York City revealed common comorbidities including hypertension (56.6%), obesity (41.7%), and diabetes (33.8%), and reported that 373 (14.2%) of patients required treatment in the intensive care unit, and 320 (12.2%) received invasive mechanical ventilation, in whom the mortality was 88.1% (282/320)]. Also, many of the studies in this analysis did not report on how many patients had underlying liver disease and if these patients were at an elevated risk of having increased LFTs in the setting of COVID-19 infection.