The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest public health challenge to the biomedical community of the last century. Despite multiple public health mea- sures,1-3 there remains an urgent need for pharmacologic therapies to treat infected patients, minimize mortality, and decrease pres- sures on intensive care units and health systems and optimally, they should also decrease subsequent transmission.
Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea ...Utai Sukviwatsirikul
Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea in children: a randomized double-blind placebo-controlled
trial
M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
Accepted for publication 24 November 2004
February 9, 2018
In the past several years, the United States has struggled to respond to viral outbreaks, such as Ebola and Zika. There is now an awareness of the need to rapidly develop vaccines and treatments for epidemics that can quickly spread from country to country. But questions remain as how to best conduct clinical trials and development of vaccines in the context of an epidemic or outbreak.
At this panel discussion, two health policy experts examined the appropriate conduct of clinical trials during public health emergencies.
Learn more at: http://petrieflom.law.harvard.edu/events/details/clinical-trials-during-public-health-emergencies
Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea ...Utai Sukviwatsirikul
Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea in children: a randomized double-blind placebo-controlled
trial
M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
Accepted for publication 24 November 2004
February 9, 2018
In the past several years, the United States has struggled to respond to viral outbreaks, such as Ebola and Zika. There is now an awareness of the need to rapidly develop vaccines and treatments for epidemics that can quickly spread from country to country. But questions remain as how to best conduct clinical trials and development of vaccines in the context of an epidemic or outbreak.
At this panel discussion, two health policy experts examined the appropriate conduct of clinical trials during public health emergencies.
Learn more at: http://petrieflom.law.harvard.edu/events/details/clinical-trials-during-public-health-emergencies
Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
This article is a preprint and has not been peer-reviewed.
Twitter: @MattisVollan
Etiologia de la celulitis y Predicción clínica de la enfermedad Estreptocócic...Alex Castañeda-Sabogal
Etiologia de la celulitis. Estudio prospectivo y predicción clínica de la infeccion por Estreptococcus basado en la frecuencia encontrada de las especies de estreptococo
Un estudio sobre las caracteristicas del tratamiento sde la TB XDR en sudafrica y el pronostico de vida de los pacientes segun las estrategias terapeuticas
The Emergence of Baricitinib: A Story of Tortoises Versus HaresJustin Stebbing
Baricitinib is a once-daily orally administered JAK1/2 inhibitor, which inhibits the signaling of many cytokines and has been approved for the treatment of moderate to severe rheumatoid arthritis (RA) based on long-term randomized dosing against both placebo and standard of care, notably tumor necrosis factor (TNF)- alpha blockade. Its use for the treatment of coronavirus disease 2019 (COVID-19) was originally suggested after a search of the extensive BenevolentAI knowledge graph for approved drugs that could be used in this pandemic An advantage of approved drugs is that they have a known safety profile and can therefore be rapidly approved in fast-moving pandemics.
Assignment on Covid 19 | Tutors India.pptxTutors India
Tutors india thesis and dissertation writing help guarantees that your dissertation is confidential, and so you do not have to worry about it.
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World: https://www.tutorsindia.com
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Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
This article is a preprint and has not been peer-reviewed.
Twitter: @MattisVollan
Etiologia de la celulitis y Predicción clínica de la enfermedad Estreptocócic...Alex Castañeda-Sabogal
Etiologia de la celulitis. Estudio prospectivo y predicción clínica de la infeccion por Estreptococcus basado en la frecuencia encontrada de las especies de estreptococo
Un estudio sobre las caracteristicas del tratamiento sde la TB XDR en sudafrica y el pronostico de vida de los pacientes segun las estrategias terapeuticas
The Emergence of Baricitinib: A Story of Tortoises Versus HaresJustin Stebbing
Baricitinib is a once-daily orally administered JAK1/2 inhibitor, which inhibits the signaling of many cytokines and has been approved for the treatment of moderate to severe rheumatoid arthritis (RA) based on long-term randomized dosing against both placebo and standard of care, notably tumor necrosis factor (TNF)- alpha blockade. Its use for the treatment of coronavirus disease 2019 (COVID-19) was originally suggested after a search of the extensive BenevolentAI knowledge graph for approved drugs that could be used in this pandemic An advantage of approved drugs is that they have a known safety profile and can therefore be rapidly approved in fast-moving pandemics.
Assignment on Covid 19 | Tutors India.pptxTutors India
Tutors india thesis and dissertation writing help guarantees that your dissertation is confidential, and so you do not have to worry about it.
For #Enquiry:
World: https://www.tutorsindia.com
UK: https://www.tutorsindia.com/uk
UAE: https://tutorsindia.com/ae/
Australia:https://www.tutorsindia.com/au/
Newzealand: https://www.tutorsindia.com/nz/
(UK): +44-1143520021
Mail: info@tutorsindia.com
Mail: info@tutorsuk.co.uk
(Whatsapp): +91-8754446690
Treatment of COVID-19; old tricks for new challengesLuisaSarlat
Coronavirus disease (COVID-19), which appeared in December 2019, presents a global challenge, particularly in the rapid increase of critically ill patients with pneumonia and absence of definitive treatment. To date, over 81,000 cases have been confirmed, with over 2700 deaths. The mortality appears to be around 2%; early published data indicate 25.9% with SARS-CoV-2 pneumonia required ICU admission and 20.1% developed acute respiratory distress syndrome
Convalescent Plasma as a COVID-19 TreatmentEMMAIntl
I think I can speak for most people when I say that viable treatments and vaccines are desperately needed at this point to overcome the COVID-19 global pandemic. Not only that COVID-19 has taken so many lives across the globe, the societal, public health and financial ramifications will be with us for years to come...
Clinical Research Centre (CRC) Perak (Hospital Ipoh, Hospital Taiping, Hospital Seri Manjung) has just released their new Network Bulletin. This edition focused on COVID-19 Vaccine Trial and COVID-19 Research Priorities.
Population-based resistance of Mycobacterium tuberculosis
isolates to pyrazinamide and fl uoroquinolones: results from
a multicountry surveillance project
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
What is the best drug for COVID-19? The need for randomized controlled trials.
1. Viewpoint
What Is the Best Drug to Treat
COVID-19? The Need for
Randomized Controlled Trials
Silvia Ottaviani1 and Justin Stebbing1,*
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
is currently the biggest public health challenge to the biomedical
community of the last century. Despite multiple public health mea-
sures,1-3
there remains an urgent need for pharmacologic therapies
to treat infected patients, minimize mortality, and decrease pres-
sures on intensive care units and health systems and optimally,
they should also decrease subsequent transmission.
At the time of writing this Viewpoint,
there are no licensed drugs to treat
COVID-19, and a search on https://
www.clinicaltrials.gov using ‘‘COVID-
19’’ as the input term yielded 657
studies. Drug-based interventions
currently fall into categories including
off label use, which includes repurposed
drugs,4,5
and newer entities, but both
categories should be given in the
context of clinical trials. In Wuhan, China,
then the epicenter of the pandemic, Cao
et al.,6
under heroic circumstances, con-
ducted a randomized, controlled, open-
label trial involving 199 hospitalized
patients with confirmed SARS-CoV-2
infection, including as an entry criteria
oxygen saturation (SaO2) of 94% or less
on air (ChiCTR2000029308). Patients
were randomly assigned 1:1 to receive
either lopinavir–ritonavir (400 mg and
100 mg, respectively) twice daily for
14 days, or standard care alone. The pri-
mary end point was the time to clinical
improvement, defined as the time from
randomization to either an improvement
of two points on a seven-category
ordinal scale or discharge from the hos-
pital, whichever came first.6
Even though
their study showed no benefits with
lopinavir–ritonavir treatment beyond
standard care, this is exactly the sort of
study that best informs our treatment
options.
Following this, we were surprised to see
that the New England Journal of Medi-
cine published a single-arm study on 61
patients who received at least one dose
of remdesevir, again with similar entry
criteria of SaO2 < 94% on air.7
Unlike
the randomized trial by Cao et al., there
was no accompanying editorial, but
there was a subsequent open letter
discussing remdesevir studies from
the CEO and Chairman of Gilead
(https://www.gilead.com/stories/articles/
an-open-letter-from-our-chairman-and-
ceo). One presumes that the patients in
the remdesevir single-arm study, and
several included in an earlier Lancet pa-
per,8
were recruited in perhaps easier
conditions than those in Wuhan earlier
this year.
Randomized trials are designed to pre-
cisely answer questions regarding
toxicity and efficacy beyond standard
of care and in the absence of an effec-
tive therapy, it remains entirely reason-
able and ethical at this point to perform
a trial versus placebo. They are much
more informative than single-arm
studies which result in claims, perhaps
borne from hope and/or desperation,
that drugs work,9
and such claims
include those from physicians stating
very high cure rates. Clearly, recruiting
patients recently diagnosed will have
‘‘cure rates’’ usually in the high 90%
range, unless one focuses on recruiting
hospitalized patients and/or the
elderly, frail, those with co-morbidities,
or a high body mass index, to name a
few examples.
A well-known French microbiologist on
social media has promoted the use of
chloroquine to treat or prevent
COVID-19. The FDA has approved it,
although at the time of writing they ha-
ven’t explained the rationale behind
the approval, and as a consequence,
patients, institutions and the worried
public have demanded immediate
chloroquine for all. The resulting rush
on chloroquine has led to severe short-
ages of the drug, and patients taking
regular chloroquine or hydroxychloro-
quine for lupus or other systemic dis-
eases had to stop their treatment due
to a lack of supply. This drug has well
known, often serious, toxicities;10
we
note one small study that was stopped
due to potential cardiac complications
(https://www.nytimes.com/2020/04/12/
health/chloroquine-coronavirus-trump.
html), and we suggest it should only be
taken in the context of a randomized or
other clinical study. This is not to sug-
gest single-arm studies are not helpful:
they inform subsequent trials including
dosage, duration, and appropriate
endpoints. For example, we have
observed11
that use of baricitinib for
10 days is associated with viral rebound
in nasopharyngeal swabs in rapidly
recovered and discharged patients
and thus have recommended longer
use in the large randomized studies in
which it is included; we suggest again
that comparisons between different
therapies or placebo are likely to yield
more informative results than random-
ized studies comparing 10 days of
1Department of Surgery and Cancer, Imperial
College, London W12 0NN, UK
*Correspondence: j.stebbing@imperial.ac.uk
https://doi.org/10.1016/j.medj.2020.04.002
Med 1, 1–2, November 1, 2020 ª 2020 Elsevier Inc. 1
ll
Please cite this article in press as: Ottaviani and Stebbing, What Is the Best Drug to Treat COVID-19? The Need for Randomized Controlled
Trials, Med (2020), https://doi.org/10.1016/j.medj.2020.04.002
2. intravenous remdesevir with 5 days
(https://benevolent.ai/news/potential-
treatment-for-covid-19-identified-by-
benevolentai-using-artificial-intelligence-
enters-clinical-testing and https://
investor.lilly.com/news-releases/news-
release-details/lilly-begins-clinical-testing-
therapies-covid-19).
With this in mind, we thoroughly
congratulate the authors from Guangz-
hou, China, who successfully random-
ized 86 individuals with mild-to-
moderate COVID-19 in a 2:2:1 design
to lopinavir/ritonavir, arbidol (a broad-
spectrum viral infusion inhibitor12
), or
placebo (NCT04252885)13
. Because
they included only mild-to-moderate pa-
tients, the pre-defined primary endpoint
was the conversion at day 21 of positive-
to-negative PCR tests for SARS-CoV-2
from nasopharyngeal swabs. The
real-time reverse-transcriptase PCR (RT-
PCR) method used was indeed appro-
priate as it was performed simulta-
neously on two target genes, ORF1ab
and N, and positive and negative con-
trols were used at each batch. Negative
conversion required two separate real
time RT-PCR tests separated by 24 h,
and the entry criteria for the definition
of mild-to-moderate including the
absence of pneumonia are entirely
appropriate. Baseline criteria between
the three groups were well-matched (a
criticism of one of the hydroxychloro-
quine randomized studies is this was
not the case14
) and follow up was appro-
priate. Their data helpfully shows there
was no difference between any of the
groups in the primary endpoint.
In the continuing search for safe and
effective new therapies to treat
patients with COVID-19, we require
well-conducted ethical studies including
prospective, randomized, placebo-
controlled clinical studies such as this.
Although many drugs have predicted
in vitro activity against the virus, the pro-
posal that such drugs might provide
more benefit than harm is not appro-
priate with no evidence base supporting
efficacy in any patients infected with
SARS-CoV-2. A preprint reporting results
from a randomized trial of the anti-viral
favipravir versus arbidol in 240 adults
has shown no difference in clinical recov-
ery at 7 days, but cough and pyrexia were
improved on favipravir.15
These authors
and Li et al. shouldbe applaudedfortheir
efforts to add a useful randomized trial to
the literature, albeit one that is negative.
It is critical to publish such studies. Inter-
national multicenter trials, such as Dis-
covery (NCT04315948) and Solidarity
(EudraCT number 2020-000982-18), will
randomize patients with COVID-19 to
receive different drugs in adaptive study
designs. Such initiatives will provide the
best and most relevant data to guide
management of patients with COVID-19.
Whether antiviral, immunomodulatory,
or antimalarial drugs could be effective
in changing the disease course in pa-
tients with either mild or severe
COVID-19 remains unknown. When pa-
tients take these off-label and recover it
is not known whether the drug was
helpful in the disease course without
randomization. Similarly, when patients
deteriorate, we do not know if they
should be continued or considered clin-
ically ineffective and stopped. Assess-
ing viral loads by PCR on nasopharyn-
geal swabs, as performed in the trial
here, will help clarify the roles of these
medicines going forward.
DECLARATION OF INTERESTS
J.S. declares his conflicts of interest
at https://www.nature.com/onc/editors
(none are relevant here).
1. Colbourn, T. (2020). COVID-19: extending or
relaxing distancing control measures. Lancet
Public Health 5, e236–e237.
2. Cowling, B.J., Ali, S.T., Ng, T.W.Y., Tsang,
T.K., Li, J.C.M., Fong, M.W., Liao, Q., Kwan,
M.Y., Lee, S.L., Chiu, S.S., et al. (2020). Impact
assessment of non-pharmaceutical
interventions against coronavirus disease
2019 and influenza in Hong Kong: an
observational study. Lancet Public Health 5,
e279–e288.
3. Prem, K., Liu, Y., Russell, T.W., Kucharski, A.J.,
Eggo, R.M., Davies, N., Jit, M., and Klepac, P.;
Centre for the Mathematical Modelling of
Infectious Diseases COVID-19 Working
Group (2020). The effect of control strategies
to reduce social mixing on outcomes of the
COVID-19 epidemic in Wuhan, China: a
modelling study. Lancet Public Health 5,
e261–e270.
4. Richardson, P., Griffin, I., Tucker, C., Smith,
D., Oechsle, O., Phelan, A., Rawling, M.,
Savory, E., and Stebbing, J. (2020). Baricitinib
as potential treatment for 2019-nCoV acute
respiratory disease. Lancet 395, e30–e31.
5. Stebbing, J., Phelan, A., Griffin, I., Tucker, C.,
Oechsle, O., Smith, D., and Richardson, P.
(2020). COVID-19: combining antiviral and
anti-inflammatory treatments. Lancet Infect.
Dis. 20, 400–402.
6. Cao, B., Wang, Y., Wen, D., Liu, W., Wang, J.,
Fan, G., Ruan, L., Song, B., Cai, Y., Wei, M.,
et al. (2020). A Trial of Lopinavir-Ritonavir in
Adults Hospitalized with Severe Covid-19.
N. Engl. J. Med. 382, 1787–1799.
7. Grein, J., Ohmagari, N., Shin, D., Diaz, G.,
Asperges, E., Castagna, A., Feldt, T., Green,
G., Green, M.L., Lescure, F.X., et al. (2020).
Compassionate Use of Remdesivir for
Patients with Severe Covid-19. N. Engl. J.
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2 Med 1, 1–2, November 1, 2020
Please cite this article in press as: Ottaviani and Stebbing, What Is the Best Drug to Treat COVID-19? The Need for Randomized Controlled
Trials, Med (2020), https://doi.org/10.1016/j.medj.2020.04.002
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