RJPHP FARMA.2020.1 (Full Issue)
RJPHP FARMA.2020.1 (Full Issue)
RJPHP FARMA.2020.1 (Full Issue)
Editor-in-Chief
PHARMACEUTICAL
Dumitru LUPULEASA, Prof. Pharm., PhD
“Carol Davila” U.M.Ph., Bucharest, Romania
President of the Romanian Society of Pharmaceutical Sciences
Deputy Editors-in-Chief
Elena DINTE, Assoc. Prof. Pharm., PhD
“Iuliu Hatieganu” U.M.Ph., Cluj-Napoca, Romania
Liviu RUS, Lecturer Pharm., PhD
“Iuliu Hatieganu” U.M.Ph., Cluj-Napoca, Romania
Ioan TOMUTA, Prof. Pharm., PhD
PRACTICE
“Iuliu Hatieganu” U.M.Ph., Cluj-Napoca, Romania
Romanian Journal of
Senior Editor
Constantin IONESCU-TIRGOVISTE, Acad., MD, PhD
“Carol Davila” U.M.Ph., Bucharest, Romania
Managing Editor
Mihai-Cristian POPESCU, MD
College of Pharmacists in Romania
EDITORIAL BOARD
Robert ANCUCEANU, Prof. Pharm., PhD – Bucharest, Romania
Victoria ARAMA, Prof., MD, PhD – Bucharest, Romania
Ionela BELU, Assoc Prof. Pharm., PhD – Craiova, Romania
Emanoil CEAUSU, Prof., MD, PhD – Bucharest, Romania
Adriana CIURBA, Prof. Pharm., PhD – Targu Mures, Romania
ASSOCIATION MEDICALE ROUMAINE
ROMANIAN MEDICAL ASSOCIATION Carmen CRISTESCU, Prof. Pharm., PhD – Timisoara, Romania
Elena DINTE, Assoc. Prof. Pharm., PhD – Cluj-Napoca, Romania
Cristina Elena DINU-PIRVU, Prof. Pharm., PhD – Bucharest,
Romania
Doina DRAGANESCU, Prof. Pharm., PhD – Bucharest, Romania
Daniel GRIGORIE, Prof., MD, PhD – Bucharest, Romania
Mircea HIRJAU, Assoc. Prof. Pharm., PhD – Bucharest, Romania
Dorin IONESCU, Assoc. Prof., MD, PhD – Bucharest, Romania
Romanian Journal of Constantin IONESCU-TIRGOVISTE, Acad., MD, PhD – Bucharest,
PHARMACEUTICAL PRACTICE Romania
Peer Reviewed Journal Dumitru LUPULEASA, Prof. Pharm., PhD – Bucharest, Romania
Vol. XIII, No. 1(50), 2020 Dalia Simona MIRON, Assoc. Prof., Pharm., PhD – Bucharest,
ISSN 2066-5563 | e-ISSN 2069-6671 Romania
ISSN-L 2066-5563 Simona NEGRES, Prof. Pharm., MD, PhD – Bucharest, Romania
DOI: 10.37897/RJPhP
Florica NICOLESCU, Prof. Pharm., PhD – Bucharest, Romania
Official Website: https://FARMA.com.ro
Lacramioara OCHIUZ, Prof. Pharm., PhD – Iasi, Romania
† Ludovic PAUN, Prof., MD, PhD – Bucharest, Romania
Publisher: AMALTEA MEDICAL
PUBLISHING HOUSE Iuliana POPOVICI, Prof. Pharm., PhD – Iasi, Romania
EDITORIAL BOARD (continued)
Gabriel Ioan PRADA, Prof., MD, PhD – Bucharest, Romania
Flavian Stefan RADULESCU, Assoc. Prof. Pharm., PhD – Bucharest, Romania
Liviu RUS, Lecturer Pharm., PhD – Cluj-Napoca, Romania
Gabriel SARAMET, Prof. Pharm., PhD – Bucharest, Romania
Valentina SOROCEANU, Prof. Pharm., PhD – Bucharest, Romania
Maria-Gabriela SULIMAN, Pharm. Pr., PhD – Bucharest, Romania
Ioan TOMUTA, Prof. Pharm., PhD – Cluj-Napoca, Romania
Camil VARI, Prof. Pharm., PhD – Targu Mures, Romania
Lavinia VLAIA, Assoc. Prof. Pharm., PhD – Timisoara, Romania
Vincentiu VLAIA, Assoc. Prof. Pharm., PhD – Timisoara, Romania
Ana-Maria VLADAREANU, Prof., MD, PhD – Bucharest, Romania
Laurian VLASE, Prof. Pharm., PhD – Cluj-Napoca, Romania
Laura VICAS, Prof. Pharm., PhD – Oradea, Romania
https://RJMP.com.ro
CONTENTS | CUPRINS
NUTRITION | NUTRIŢIE
Fruits – essential foods___________________________________________________________________________ 13
Fructele – alimente esenţiale
Tatiana Rosca, Maria-Gabriela Suliman
AT PRESENT | ACTUALITATE
Collaboration between pharmacist and family doctor in the Netherlands___________________________________ 18
Colaborarea dintre farmacist şi medicul de familie în Ţările de Jos
Marinela Olăroiu
HISTORY OF MEDICINE
1900, mai 15, Bucureşti – 120 ani amplă retrospectivă la sala „Dalles”,
de la naşterea prof. univ. dr. Artur I. în acelaşi an [14].
Kreindler (†1988, Bucureşti)
1920, apr. 14, Sadagura, jud.
După ce a absolvit liceul „Gh.
Cernăuţi – 100 ani de la naşterea
Lazăr“, a urmat cursurile Facultăţii
dr. Ştefan-Gheorghe Bucevschi
de Medicină din Bucureşti (1919-
(†1999, apr. 26, Bârlad)
1925), obţinând titlul de doctor cu
teza „Tonusul vegetativ şi probele Absolvent al Liceului „Aron
sale farmacologice”; stagii de Pumnul“ din Cernăuţi; licenţiat al
specializare la Paris (1926-1927); Facultăţii de Medicină din Cluj
asistent (1927-1940); şef de lucrări (1944); a fost incorporat şi a luat
(1944-1947); conf. univ. (1947- parte la campaniile din Vest
1948) la Clinica de neurologie a (1944-1945); medic la Sibiu
Facultăţii de Medicină din (1945-1950) şi apoi la Bârlad din
Bucureşti; medic primar neurolog 1950; a scris circa 300 de studii şi
(1931) şi docent universitar în articole medicale, în parte publicate
neurologie (1932); profesor la în diferite ziare şi reviste; specializat
şcoala de medicină pentru evrei în obstetrică-ginecologie; în paralel,
(1942-1944) şi profesor universitar a desfăşurat o susţinută activitate
la Clinica de neurologie a I.M.F. scriitoricească (redactor la revista
Bucureşti (1948-1970); director al „Coordonate bârlădene“; a
Institutului de Neurologie al îndrumat cenaclul literar „Ferestre
Academiei; membru titular al spre lumină“; a scris piese de teatru
Academiei Române (1948) şi al („Opriţi-l pe Dik Waring“, „Fiare şi
Academiei de Ştiinţe Medicale oameni”, „Transplantul“, “Vagonul
(1969); „Om de ştiinţă emerit” de clasa I“, „Vâlvătaia”, „Turbinca lui
(1962); membru a numeroase Ivan“, „Întoarcerea lui Tomiţă“), ce
Societăţi de neurologie din lume; a s-au jucat pe scenele bârlădene; a
fost unul dintre cei mai renumiţi lăsat în manuscris câteva volume de
corifei ai şcolii româneşti de proză: „Istoria romanţată a
neurologie, fondată de prof. Gh. Bucovinei“, „Cuţitul de aur“,
Marinescu [13]. „Minciuna“, fragmente din ultima
lucrare istorico-literară au fost
1910, mai 19, Craiova – 110 ani de publicate în Almanahul cernăuţean
la naşterea pictorului, biolog şi „Ţara Fagilor“ [15;16].
medic Ion Ţuculescu (†1962, iulie
27, Bucureşti) 1925, apr. 21, Topalu, jud.
Constanţa – 95 ani de la naşterea
Medic şi licenţiat în ştiinţele naturii
col. dr. Nicolae Necula (†1998,
(1939), a început să picteze în
mai 9)
paralel cu studiile sale ştiinţifice.
Lucrările realizate până către 1947 A urmat Facultatea de Medicină
se înscriu ca realist-expresioniste Generală din Cluj, pe care a
sau realism popular, apoi, spre absolvit-o în 1950; şef de secţie Boli
sfârşitul vieţii, către abstracţionism, contagioase în Spitalele militare din
având şi o etapă originală închinată Cluj, Craiova, Constanţa.
totemurilor populare.
În anul 1990, se pensionează cu
În 1965, s-a publicat postum gradul de colonel şi se încadrează la
lucrarea ştiinţifică „Biodinamica Facultatea de Medicină din
FIGURA 10. Dr. Ion Ţuculescu, lacului Techirghiol“ a medicului- Constanţa ca profesor asociat la
Autoportret
pictor, căruia i-a fost organizată şi o Disciplina de Istoria Medicinei
BIBLIOGRAFIE
Rezumat
Ar putea fructele să reducă inflamaţia în organism, să susţină sistemul imunitar şi pe cel hormonal, stimuleze detoxi-
fierea şi să moduleze microbiomul? La aceste întrebări, răspunsul poate fi sintetizat astfel: fructul este un aliment esenţi-
al deoarece corpul consumă minimum de energie pentru a-l digera şi obţine o rentabilitate maximă.
Cuvinte cheie: fructe, inflamaţie, sistem imun, sistem hormonal, detoxifiere, microbiom
Abstract
What could fruits do? Reduce the inflammation in the organism, support the immune system, the hormonal system and
detoxificatio, modulate the microbiome? The answer to these questions can be summarized as follows: the fruit is an es-
sential food because the body consumes a minimal amount of energy to digest it and achieves maximum return.
Keywords: fruits, inflammation, immune system, hormonal system, detoxification, microbiome
PRUNELE NEGRE
Conţin 4.873 de antioxidanţi,
potrivit unui studiu publicat în
Jurnalul de chimie agricolă și
alimentară. Prunele pot ajuta, de
asemenea, la creșterea rezistenţei
osoase.
CIREŞELE
Reprezintă cea mai bună sursă de
melatonină antioxidantă.
Melatonina protejează pielea
împotriva radiaţiilor ultraviolete și
stimulează creșterea celulelor pielii,
reglează ciclul somn-veghe,
mărește producţia de citokine.
Cireșele conţin şi vitamina C, care
este necesară pentru a construi
colagenul – „schela“ naturală a
pielii și factor determinant în
FIGURA 1. Sucurile din fructe furnizează polifenoli, oligozaharide şi fibre, inducând un prevenirea ridurilor.
efect asemănător prebioticului (4)
S-a făcut următorul experiment: 20 au fost parţial inversate în ziua 17. diversitatea și funcţia comunităţilor
de adulţi sănătoși au consumat Concluzia a fost că o dietă de 3 zile microbiene prezente în și pe
doar sucuri de legume/fructe timp pe bază de suc a modificat ţesuturile plantelor.
de 3 zile, urmate de 14 zile de dietă microbiota intestinală, asociată cu Microorganismele sunt o parte
obișnuită. În ziua a 4-a, s-a observat pierderea în greutate, creșterea integrantă a compoziţiei fructelor și
o scădere semnificativă a greutăţii vasodilatatorului NO și scăderea legumelor și se găsesc ca epifite la
și a indicelui de masă corporală oxidării lipidelor (4). suprafaţă sau ca endofite în
(p = 2,0E-05), care a fost menţinută ţesuturi. Studiile despre
Se discută însă și despre un
până în ziua 17 (p = 3,0E-04). În ziua microbiomul fructelor au
microbiom al fructelor care este, de
a 4-a, proporţia Firmicutes și a potenţialul de a furniza cunoștinţe
asemenea, foarte important.
proteobacteriilor din filon a scăzut care vor conduce la o schimbare
Tehnologiile avansate de
semnificativ, iar Bacteroidetes și fundamentală a paradigmei în
secvenţiere ADN au sporit
cianobacteriile au fost crescute modul în care gândim strategiile de
capacitatea de a caracteriza
comparativ cu valoarea de bază și
BIBLIOGRAFIE
1. Fahey JW, Zalcmann AT, Talalay P. The Chemical Diversity and Distribution of Glucosinolates and
Isothiocyanates Among Plants. Phytochemistry. 2001;56(1):5-51.
2. Ryan KK, Seeley RJ. Physiology. Food as a Hormone. Science. 2013 Feb 22;339(6122):918-9.
3. Murray IA, Perdew GH. Ligand activation of the Ah receptor contributes to gastrointestinal
homeostasis. Curr Opin Toxicol. 2017;2:15-23.
4. Henning SM, Yang J, Shao P et al. Health benefit of vegetable/fruit juice-based diet: Role of
microbiome. Sci Rep 2017;7:2167.
5. Danesi F, Ferguson LR. Could Pomegranate Juice Help in the Control of Inflammatory Diseases?
Nutrients. 2017; 9(9):958.
6. Ercolini D, Fogliano V. Food Design To Feed the Human Gut Microbiota. J. Agric. Food Chem.
2018;66:3754-8.
7. Setchell KDR, Clerici KDR. Equol: History, Chemistry, and Formation. J. Nutr. 2010;
140(7):1355S-1362S.
8. Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, Tuohy K. Gut Microbiota Functions:
Metabolism of Nutrients and Other Food Components. Eur J Nutr. 2018;57(1):1-24.
9. Drobya S, Wisniewski M. The fruit microbiome: A new frontier for postharvest biocontrol and
postharvest biology. Postharvest Biology and Technology 2018;140:107-112.
Collaboration between
pharmacist and family
doctor in the Netherlands
Colaborarea dintre farmacist şi
medicul de familie în Ţările de Jos
Dr. Marinela Olăroiu
medic medicină de familie, geriatrie-gerontologie, doctor în ştiinţe
medicale, secretar SOAZE/RACE (Research and Advice în Care of Elderly),
Redactor șef „Revista română de medicina familiei“
Rezumat
Colaborarea dintre profesioniştii din sănătate contribuie la îmbunătăţirea şi menţinerea la un înalt nivel a calităţii
serviciilor din sănătate. În prima linie, medicul de familie şi farmacistul au în comun autonomia organizării propriei ac-
tivităţi şi faptul că au dezvoltat modele de colaborare şi de integrare a activităţilor pentru a lucra împreună în folosul
pacienţilor.
Conlucrarea dintre medicii de familie şi farmacişti se poate face în grupuri de lucru, proiecte, într-un cadru organizat,
structurat, sau informal, ad-hoc ori de câte ori este nevoie. Temele abordate se referă la prescrierea medicamentelor şi eli-
berarea reţetelor, evitarea şi limitarea incidentelor, a efectelor adverse şi a polifarmaciei sau la instruirea pacienţilor, limi-
tarea costurilor, evaluarea de medicamente noi.
În Ţările de Jos există o lungă tradiţie şi diferite modalităţi de colaborare între medicul de familie şi farmacist cu scopul
de a satisface nevoile medicale în continuă creştere şi, mai ales, în continuă schimbare ale pacienţilor.
Cuvinte cheie: medic de familie, farmacist, lucru în echipă, grup de lucru, asistenţă medicală primară
Abstract
Collaboration between health professionals contributes to improving and maintaining a high level of quality of health
services. In the first line, the family doctor and the pharmacist have in common the autonomy of organizing their own
activity and the fact that they have developed models of collaboration and integration of activities to work together for the
benefit of patients.
Collaboration between family doctors and pharmacists can be done in working groups, projects, in an organized, struc-
tured or informal setting whenever needed. Topics covered include prescribing and issuing medical recipes, avoiding and
limiting incidents, side effects and polypharmacy or training the patients, limiting costs and evaluating new drugs.
In the Netherlands there is a long tradition and different ways of collaboration between the family doctor and the phar-
macist in order to meet the growing and especially changing medical needs of patients.
Keywords: family doctor, pharmacist, teamwork, working group, primary care
comunicarea dintre ei. Astfel, târziu în aceeaşi zi sau în zilele mai departe la farmacie folosind un
farmaciştii sună mai des medicii de următoare de la recepţia sistem informatic de legătură.
familie, un sfert dintre ei sună zilnic cabinetului/grupului de practică. De
3. Informarea pacientului despre
şi 40% dintre ei sună săptămânal, asemenea, poate opta să îi fie modul de acţiune şi efectele
faţă de 15% şi 31% în cazul trimise acasă medicamentele prin secundare ale medicamentelor.
medicilor de familie. poştă, curier. Instrucţiunile sunt elaborate
Schimburile de informaţii dintre
2. Prelungirea prescripţiilor în cazul împreună de farmacişti şi de
cele două părţi se fac în ultimii ani
bolilor cronice. Aproape în fiecare medicii de familie şi sunt oferite în
din ce în ce mai des prin alte
cabinet/grup de practică de scris sau verbal, adesea telefonic şi
mijloace de comunicare digitale,
medicina familiei pacienţii pot reluate de câte ori este nevoie.
prin sisteme de comunicare
solicita telefonic repetarea
standardizate, cu circuit închis.
prescripţiilor medicale, comunicând CONCLUZII
direct unui operator sau Colaborarea medic de familie –
B. Colaborarea la nivel de servicii
înregistrând un mesaj care conţine farmacist este esenţială în buna
legate de prescrierea şi eliberarea
numele şi data naşterii pacientului, funcţionare a sistemului de
medicamentelor
denumirea medicamentului, doza asistenţă medicală şi un element de
Majoritatea cabinetelor de
zilnică şi pentru ce perioadă de bază al serviciilor personalizate.
medicină a familiei oferă pacienţilor
timp. Dacă solicitarea este Atât medicul, cât şi farmacistul
mai multe tipuri de servicii în
efectuată înainte de o anumită oră trebuie să cunoască în orice
colaborare cu farmaciile din
a dimineţii (de exemplu, ora 11 moment medicamentele pe care le
apropiere referitor la prescrierea şi
a.m.), medicamentele pot fi ridicate întrebuinţează pacientul.
eliberarea de medicamente sau
de la cabinet/grup de practică în
instruirea pacienţilor. Iată câteva În acest context, schimbul de
exemple: aceeaşi zi după ora 16 p.m., dacă
informaţii şi menţinerea deschisă a
1. Trimiterea prescripţiilor online la nu, începând de a doua zi. În
canalelor de comunicare dintre ei
farmacia la care este arondat acordarea acestui serviciu, un rol
este de mare importanţă în
pacientul sau cu care colaborează important îl are aşa-numita
prevenirea efectelor adverse ale
cabinetul. În acest fel, pacientul nu „asistentă a medicului“, care se
medicamentelor, polifarmaciei şi
se mai deplasează la farmacie şi ocupă de verificarea informaţiilor
incidentelor legate prescriere şi
poate ridica medicamentele mai primite telefonic şi retrimiterea lor
modul de administrare.
BIBLIOGRAFIE
1. NIVEL Raport. Samenwerking tussen huisarts en openbaar apotheker: stând van zaken en
mogelijkheden voor de toekomst. ISBN 978-94-6122-376-0. 2016 NIVEL, Postbus 1568, 3500
BN Utrecht, pp. 10,16,20,36,49.
2. Cambach W, Essink R. De Kwaliteti van het FTO overleg în beeld. [FTOpll 2011]. [The quality of
the pharmacotherapeutic consultations oulined]. Utrecht: Instituut voor Verantwoord
Medicijngebruik (IVM);2012.Dec.
3. NHG-Standpunt Toekomstvisie Huisartsenzorg ‘’Farmacotherapiebeleid in de huisartsenzorg’’.
Utrecht: Colofon; 2006.
4. Canadian Medical Education Directives for Specialists. Available from: https://www.nspoh.nl/
canmeds / [Accessed 30th April 2020].
Agenţia Naţională a
Medicamentului şi a Lansarea sistemului
Dispozitivelor Medicale din
România prezintă în cele ce consolidat de monitorizare
urmează traducerea în limba
română a comunicatului de a disponibilității
presă al Agenţiei Europene a
Medicamentului (European medicamentelor utilizate
Medicines Agency = EMA)
referitor la lansarea sistemului pentru tratarea infecției
consolidat de monitorizare a
disponibilității medicamentelor COVID-19
utilizate pentru tratarea
infecției COVID-19.
EMA, 21 aprilie 2020
EMA, împreună cu industria toate situațiile actuale și anticipate Sistemul a fost înființat de către
farmaceutică și statele membre ale de deficit de medicamente utilizate Grupul de Coordonare Executivă a
UE, a lansat sistemul său consolidat la pacienții cu infecția COVID-19, cu UE pe probleme de deficit de
de monitorizare rapidă în sprijinul privire la medicamentele autorizate medicamente cauzat de
prevenirii și diminuării problemelor prin procedură atât centralizată, cât evenimente majore, care asigură
de aprovizionare cu medicamente și națională. conducere strategică pentru acțiuni
esențiale utilizate pentru tratarea Noul mecanism va permite o mai urgente și coordonate privind lipsa
pacienților cu infecția COVID-19. bună supraveghere a problemelor de medicamente în UE în contextul
curente de aprovizionare precum și pandemic actual provocat de
Conform prevederilor acestui infecția COVID-19. EMA îi revine
un schimb mai rapid de informații
sistem, fiecare companie între autoritățile de reglementare rolul de coordonare a informațiilor
farmaceutică stabilește un punct din UE și industria farmaceutică, în primite de la companiile
unic de contact (punct unic de scopul atenuării și prevenirii farmaceutice cu privire la situațiile
contact la nivel de industrie - deficitelor de medicamente de deficit de aprovizionare și de
i-SPOC) care va raporta către EMA utilizate pe perioada situației de comunicare a acestora către Grupul
și autoritățile competente naționale urgență de sănătate COVID-19. de Coordonare Executivă a UE, care
Agenţia Naţională a
Medicamentului şi a Evidențierea de
Dispozitivelor Medicale din
România prezintă în cele ce către autoritățile de
reglementare din întreaga
urmează traducerea în limba
română a comunicatului de
presă al Agenţiei Europene a
Medicamentului (European
Medicines Agency = EMA)
lume a necesității de
referitor la evidențierea de
către autoritățile de
dovezi solide cu privire
reglementare din întreaga
lume a necesității de dovezi la tratamentele utilizate
pentru combaterea
solide cu privire la
tratamentele utilizate pentru
infecției COVID-19
combaterea infecției
COVID-19.
EMA, 9 aprilie 2020
Autoritățile internaționale de Medicamentului, sub egida Coaliției pentru investigație clinică sau
reglementare au publicat astăzi un Internaționale a Autorităților de medicamente adaptate care ar
raport care evidențiază opiniile și Reglementare din domeniul prezenta profilul de siguranță și
argumentele acestora cu privire la Medicamentului (International eficacitate necesar pentru
dezvoltarea unor potențiale terapii Coalition of Medicines Regulatory administrare în tratamentul
împotriva infecției COVID-19, Authorities = ICMRA). COVID-19 constituie cea mai rapidă
efectuarea de studii clinice și modalitate de acțiune în beneficiul
programe de utilizare compasională În momentul de față, niciun
pacienților. Autoritățile de
a unor medicamente (tratament de medicament nu prezintă încă reglementare au convenit că
ultima instanta). Raportul prezintă eficacitate demonstrată în tratarea studiile controlate randomizate
rezultatele unui workshop referitor infecției COVID-19. Participanții la multicentrice sunt cea mai bună
la dezvoltarea de medicamente workshop au subliniat faptul că metodă de generare a datelor
pentru tratarea infecției COVID-19, strângerea de dovezi solide pentru necesare pentru dezvoltarea rapidă
organizat de Agenţia Europeană a stabilirea acelor medicamente a unor potențiale tratamente a
"Currently there are no targeted the virus and assess how much of drug leads that would have to go
therapeutics or effective treatment each compound is required to stop through this process from scratch."
options for COVID-19," Professor the enzyme from working or to kill
After the enzyme's structure was
Guddat said. the virus.
made public, the team received
"If the amount is small, then we
"In order to rapidly discover lead more than 300 requests for more
have a promising compound for
compounds for clinical use, we information, even before the paper
further studies."
initiated a program of high- was published.
throughput drug screening, both in After assaying thousands of drugs, "To provide an analogy, we've
laboratories and also using the researchers found of the six that provided scientists with a fishing
latest computer software to predict appear to be effective in inhibiting pole, the line and the exact bait,
how different drugs bind to the the enzyme, one is of particular and have in only one month caught
virus. interest. some fish," Professor Guddat said.
Professor Guddat said the project "We're particularly looking at "Now it's up to us and the other
targeted the main COVID-19 virus several leads that have been fisherman - our fellow scientists
enzyme, known as the main subjected to clinical trials including globally - to take full advantage of
protease or Mpro, which plays a for the prevention and treatment of this breakthrough."
pivotal role in mediating viral various disorders such as
"With continued and up-scaled
replication. cardiovascular diseases, arthritis,
efforts we are optimistic that new
stroke, atherosclerosis and cancer,"
"This makes it an attractive drug candidates can enter the COVID-19
Professor Guddat said.
target for this virus, and as people drug discovery pipeline in the near
don't naturally have this enzyme, "Compounds that are already along future."
compounds that target it are likely the pipeline to drug discovery are
to have low toxicity. preferred, as they can be further
tested as antivirals at an
"We add the drugs directly to the
accelerated rate compared to new
enzyme or to cell cultures growing
Reference
Zhenming Jin, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, Xiaofeng Li, Leike Zhang, Chao Peng, Yinkai Duan, Jing Yu,
Lin Wang, Kailin Yang, Fengjiang Liu, Rendi Jiang, Xinglou Yang, Tian You, Xiaoce Liu, Xiuna Yang, Fang Bai, Hong Liu, Xiang Liu, Luke W Guddat,
Wenqing Xu, Gengfu Xiao, Chengfeng Qin, Zhengli Shi, Hualiang Jiang, Zihe Rao, Haitao Yang. Structure of Mpro from COVID-19 virus and discovery of
its inhibitors. Nature, 2020. doi: 10.1038/s41586-020-2223-y.
Potential harms of
chloroquine,
hydroxychloroquine and
azithromycin for treating
COVID-19
"Physicians and patients should be • Interactions with other drugs The review summarizes the poor
aware of several rare but • Metabolic variability (some quality of evidence suggesting that
potentially life-threatening adverse people metabolize these treatments might be
effects of chloroquine and chloroquine and beneficial in patients with
hydroxychloroquine," says Dr. David hydroxychloroquine poorly COVID-19 and cautions that it is
Juurlink, Division of Clinical and a small percentage possible that these treatments
Pharmacology and Toxicology, metabolize them rapidly, could worsen the disease.
Sunnybrook Health Sciences which affects the response
to treatment) "Despite optimism (in some, even
Centre, and a senior scientist at
• Overdose (chloroquine and enthusiasm) for the potential of
ICES.
hydroxychloroquine are chloroquine or hydroxychloroquine
The review provides an overview of highly toxic in overdose and in the treatment of COVID-19, little
potential harms associated with can cause seizures, coma and consideration has been given to the
these drugs as well as their cardiac arrest) possibility that the drugs might
management based on the best • Drug shortages (patients with negatively influence the course of
available evidence. autoimmune disorders such disease," says Dr. Juurlink. "This is
as rheumatoid arthritis, lupus why we need a better evidence
Potential adverse effects include
and other chronic diseases, base before routinely using these
• Cardiac arrhythmias
who take hydroxychloroquine drugs to treat patients with
• Hypoglycemia
to treat these conditions COVID-19."
• Neuropsychiatric effects,
could have problems
such as agitation, confusion,
accessing this drug)
hallucinations and paranoia
Reference
David N Juurlink. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in
the management of SARS-CoV-2 infection. CMAJ 2020. doi: 10.1503/cmaj.200528.
"The solution is to find an optimal team describes the REMAP-CAP on the fly as plates come back
tradeoff between doing something platform in a manuscript published scraped clean or barely touched,
now, such as prescribing a drug in the Annals of the American until hitting on the combination
off-label, or waiting until traditional Thoracic Society (AnnalsATS). that sells best.
clinical trials are complete," said REMAP (randomized, embedded, The UPMC-REMAP-COVID19 trial,
Derek Angus, M.D., M.P.H., multi-factorial, adaptive platform) built on the backbone of the
professor and chair, Department of allows researchers to rapidly test REMAP-CAP platform, will be
Critical Care Medicine at Pitt and multiple treatment approaches particularly powerful because it is
UPMC. "We've developed a way to simultaneously at a lower cost and being integrated with the electronic
do that with an adaptive clinical with fewer patients than traditional health record system at UPMC,
trial model that relies on a type of clinical trials. The REMAP design, noted Angus. "In a pandemic,
artificial intelligence known as first described by Angus in 2015 in doctors will not have the time to
reinforcement learning to identify the Journal of the American debate the pros and cons of every
the best, evidence-backed therapy Medical Association (JAMA), is a possible clinical trial. By building
for COVID-19 much faster than flexible version of what are called this one-stop solution at the
using the traditional scientific "adaptive platform trials." point-of-care, we are rolling out an
approach." "Adaptive platform trials are rapidly approach that can assure that every
Before COVID-19 emerged, Angus being endorsed by the U.S. Food patient admitted with COVID-19, if
and a wide range of international and Drug Administration, the Bill & they choose to, can be enrolled in
collaborators had developed a Melinda Gates Foundation and the program."
platform, called REMAP-Community others as a long-needed revolution
"We must throw out old ways of
Acquired Pneumonia (REMAP-CAP), in clinical trials," said Angus, who
thinking and fuse clinical care and
designed to find optimal holds the Mitchell P. Fink Endowed
clinical research into one extremely
treatments for severe pneumonia Chair at Pitt.
efficient system," said Angus, who
both in non-pandemic and He compares the REMAP approach authored a recent viewpoint in
pandemic settings. When COVID-19 to a chef offering a prix fixe menu JAMA advocating for the "learning
began circulating, REMAP-CAP was with appetizer, main course and while doing" approach. "This is an
rapidly adapted, as per its intent, to dessert. The chef may try various unprecedented pandemic and we
incorporate additional treatment combinations, serving sizes and need an unprecedented response."
regimens specifically targeting the options, sometimes leaving out the
UPMC-REMAP-COVID19 will open
SARS-CoV-2 virus. The international appetizer or dessert, and adjusting
across UPMC's 40-hospital system Furthermore, because the UPMC- country to participate in this trial.
and begin with multiple treatments REMAP-COVID19 platform is As more institutions join, the model
tested simultaneously in different connected to the worldwide learns faster."
combinations - including REMAP-CAP, the trial learns from
If one of the treatments shows
hydroxychloroquine, steroids and the entire international experience.
early signs of performing better
medications called REMAP-CAP is enrolling patients
than the others, patients are
immunomodulators that alter the with COVID-19 in North America,
automatically enrolled more often
responsiveness of the immune Europe, Australia and New Zealand,
into that treatment option.
system. If new drugs need to be and expanding rapidly.
Physicians can be assured that they
tested, they are simply rolled into
"The trial design uses a machine- are always betting on the winning
the platform as study amendments,
learning model that incorporates horse in the moment, and poorly
rather than tested in separate
data from patients enrolled across performing options are quickly
free-standing trials. All participants
the world to continuously learn discontinued.
will receive the current standard of
which therapies and combinations
care, and most also will receive "This allows us to always rapidly
of therapies are performing best,"
one, two or three of the identify which treatment works
explained AnnalsATS co-author
experimental treatment options. best, while keeping the number of
Scott Berry, Ph.D., president and
This means that, at launch, only patients needed to achieve
senior statistical scientist of Berry
12.5% of participants will be strictly statistical significance low," said
Consultants, who worked with
assigned to the placebo arm of the Angus. "It also means we get the
Angus and his colleagues to build
trial and, within weeks, researchers best treatment to the most patients
the statistical model. "Last week,
expect that about 99% of patients right out of the gate."
the Chief Medical Officer of the
will be receiving one or more active
United Kingdom's National Health
therapies specifically targeting
Service urged every hospital in the
COVID-19.
Reference
Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, van Bentum-Puijk W, Bhimani Z, Bonten M,
Broglio K, Brunkhorst F, Cheng AC, Chiche JD, De Jong M, Detry M, Goossens H, Gordon A, Green C,
Higgins AM, Hullegie SJ, Kruger P, Lamontagne F, Litton E, Marshall J, McGlothlin A, McGuinness S,
Mouncey P, Murthy S, Nichol A, O’Neill GK, Parke R, Parker J, Rohde G, Rowan K, Turner A, Young P,
Derde L, McArthur C, Webb SA. The Randomized Embedded Multifactorial Adaptive Platform for
Community-acquired Pneumonia (REMAP-CAP) Study: Rationale and Design. Ann Am Thorac Soc.
2020 Apr 8. doi: 10.1513/AnnalsATS.202003-192SD
research team will rely on courier commonly used at scale in low- days, as this is the current
and virtual or phone meetings with resource settings. This means it estimated incubation period for
participants. could be easily scaleable not just in COVID-19.
Canada, but internationally, if we
This type of a study is called a ring "If this strategy works, it could be a
are able to demonstrate its
trial design and was an effective major turning point in our global
effectiveness in the prevention of
method of using vaccines to effort to stop a virus where, as we
COVID-19," says Dr. Chan, who is
eradicate smallpox and test have seen, the outcomes can be
also an infectious diseases
treatments for Ebola. devastating," says Dr. Tan. "We are
physician at Sunnybrook Health
hopeful that our work will bring us
"Kaletra is a drug that the HIV Sciences Centre.
closer to understanding how to
community has been using globally
Participants randomized to receive slow or contain the spread of
for two decades, and has also been
the study drug will take it for 14 COVID-19."
Reference
This research is funded by the Canadian Institutes of Health Research and the St. Michael’s
Hospital Foundation. For the purposes of this trial, the medication, Kaletra, has been donated
in-kind by AbbVie, a biopharmaceutical company. The CIHR Centre for REACH in HIV/AIDS is also
supporting this work.
Vitamin D linked to
low virus death rate
Previous observational studies have Europe, due to the consumption of "A previous study found that 75%
reported an association between cod liver oil and vitamin D of people in institutions, such as
low levels of vitamin D and supplements, and possibly less sun hospitals and care homes, were
susceptibility to acute respiratory avoidance. Scandinavian nations severely deficient in vitamin D. We
tract infections. Vitamin D are among the countries with the suggest it would be advisable to
modulates the response of white lowest number of COVID-19 cases perform dedicated studies looking
blood cells, preventing them from and mortality rates per head of at vitamin D levels in COVID-19
releasing too many inflammatory population in Europe. patients with different degrees of
cytokines. The COVID-19 virus is disease severity."
Dr Lee Smith, Reader in Physical
known to cause an excess of
Activity and Public Health at Anglia Mr Petre Cristian Ilie, lead urologist
pro-inflammatory cytokines.
Ruskin University, said: "We found a of Queen Elizabeth Hospital King's
Italy and Spain have both significant crude relationship Lynn NHS Foundation Trust, said:
experienced high COVID-19 between average vitamin D levels "Our study does have limitations
mortality rates, and the new study and the number COVID-19 cases, however, not least because the
shows that both countries have and particularly COVID-19 mortality number of cases in each country is
lower average vitamin D levels than rates, per head of population across affected by the number of tests
most northern European countries. the 20 European countries. performed, as well as the different
This is partly because people in measures taken by each country to
"Vitamin D has been shown to
southern Europe, particularly the prevent the spread of infection.
protect against acute respiratory
elderly, avoid strong sun, while skin Finally, and importantly, one must
infections, and older adults, the
pigmentation also reduces natural remember correlation does not
group most deficient in vitamin D,
vitamin D synthesis. necessarily mean causation."
are also the ones most seriously
The highest average levels of affected by COVID-19.
vitamin D are found in northern
Reference
Petre Cristian Ilie, Simina Stefanescu, Lee Smith. The role of vitamin D in the prevention of
coronavirus disease 2019 infection and mortality. Aging Clinical and Experimental Research, 2020.
doi: 10.1007/s40520-020-01570-8.
ARDS is often caused by a serious were treated only with interferons and prevent both the body's own
viral or bacterial infection. Type I was 10.6 percent, but the addition and administered interferon from
interferons alpha and beta (IFNs) of glucocorticoids increased the fighting against the disease.
are signalling proteins produced by death rate to 39.7 percent.
"This is probably the most
the human body and they are
important observation for saving
needed in fighting off viral Glucocorticoids human lives that I have made in my
infections. For this reason, IFNs inhibit interferon career. After we overcame the
have been used successfully in
signalling and immense disappointment caused
treating ARDS in early-phase clinical
increase mortality by the results of the INTEREST trial,
trials. However, in a recently
we became sure that there had to
published later-phase clinical trial At the MediCity Research
be an explanation - and now we
(INTEREST), this effect was no Laboratory of the University of
have found it", says Professor Sirpa
longer observed. The trial was Turku, Finland, the research groups
Jalkanen.
carried out as an international of Academician, Professor Sirpa
study covering 300 patients at Jalkanen and Academy Research The findings are extremely
different medical centres. Fellow Maija Hollmén investigated important especially during the
what caused this abrupt increase in current pandemic, as the COVID-19
A closer analysis revealed that most
death rates. disease incapacitates the body's IFN
patients who participated in the
production. WHO has already
study had received glucocorticoids The researchers demonstrated with
forbidden the use of glucocorticoids
in addition to IFN beta, which cell and tissue cultures that
in treating COVID-19.
proved to be exceedingly harmful. glucocorticoids inhibit IFN signalling
The death rate of patients who
Reference
Juho Jalkanen, Ville Pettilä, Teppo Huttunen, Maija Hollmén, Sirpa Jalkanen. Glucocorticoids inhibit
type I IFN beta signaling and the upregulation of CD73 in human lung. Intensive Care Med, 2020.
doi: 10.1007/s00134-020-06086-3.
The study began on Feb. 21, 2020 analysis with NIAID. NIAID quickly significant and are based on an
and enrolled 1,063 participants in made the primary results of the analysis of 1059 participants (538
10 countries in 58 days. Patients study public due to the implications who received remdesivir and 521
provided informed consent to for both patients currently in the who received placebo). Clinicians
participate in the trial and were study and for public health. The tracked patients' clinical status daily
randomly assigned to receive local report published today in The New using an eight-point ordinal scale
standard care and a 10-day course England Journal of Medicine ranging from fully recovered to
of the antiviral remdesivir describes the preliminary results of death. Investigators also compared
intravenously, developed by Gilead the trial. clinical status between the study
Sciences, Inc., or local standard care arms on day 15 and found that the
The report notes that patients who
and a placebo. The trial was odds of improvement in the ordinal
received remdesivir had a shorter
double-blind, meaning neither scale were higher in the remdesivir
time to recovery than those who
investigators nor participants knew arm than in the placebo arm. Trial
received placebo. The study
who was receiving remdesivir or results also suggested a survival
defined recovery as being
placebo. benefit, with a 14-day mortality
discharged from the hospital or
The trial closed to enrollment on rate of 7.1% for the group receiving
being medically stable enough to
April 19, 2020. On April 27, 2020 remdesivir versus 11.9% for the
be discharged from the hospital.
(while participant follow-up was placebo group; however, the
The median time to recovery was
still ongoing), an independent data difference in mortality was not
11 days for patients treated with
and safety monitoring board statistically significant.
remdesivir compared with 15 days
overseeing the trial reviewed data for those who received placebo. Ultimately, the findings support
and shared their preliminary The findings are statistically remdesivir as the standard therapy
for patients hospitalized with arm indicates the need to evaluate began a clinical trial (known as
COVID-19 and requiring antivirals with other therapeutic ACTT 2) evaluating remdesivir in
supplemental oxygen therapy, agents to continue to improve combination with the anti-
according to the authors. However, clinical outcomes for patients with inflammatory drug baricitinib
they note that the mortality rate of COVID-19. On May 8, 2020, NIAID compared with remdesivir alone.
7.1% at 14 days in the remdesivir
Reference
John H Beigel, Kay M Tomashek, Lori E Dodd, Aneesh K Mehta, Barry S Zingman, Andre C Kalil,
Elizabeth Hohmann, Helen Y Chu, Annie Luetkemeyer, Susan Kline, Diego Lopez de Castilla,
Robert W Finberg, Kerry Dierberg, Victor Tapson, Lanny Hsieh, Thomas F Patterson, Roger Paredes,
Daniel A Sweeney, William R Short, Giota Touloumi, David Chien Lye, Norio Ohmagari,
Myoung-don Oh, Guillermo M Ruiz-Palacios, Thomas Benfield, Gerd Fätkenheuer, Mark G
Kortepeter, Robert L Atmar, C Buddy Creech, Jens Lundgren, Abdel G Babiker, Sarah Pett,
James D Neaton, Timothy H Burgess, Tyler Bonnett, Michelle Green, Mat Makowski, Anu Osinusi,
Seema Nayak, H Clifford Lane for the ACTT-1 Study Group Members. Remdesivir for the Treatment
of COVID-19 - Preliminary Report. The New England Journal of Medicine, 2020. doi: 10.1056/
NEJMoa2007764.
After evaluation please give as one of the following recommendations regarding the publication of the
manuscript:
1. Accept as it is. The manuscript makes a significant and unique contribution to current knowledge, the
research design and the results are appropriate, clearly presented, and describes the methodology is
presented with sufficient details to be verifiable. The English language is appropriate and understandable.
2. Accept after minor revisions. The manuscript could be acceptable for publication, but need either benefit
from specific changes to improve overall quality of presentation or corrections regarding some minor
methodological errors, or the English language must be verified by a proficiency speaker. Reviewers
should clearly and specifically mention areas were the manuscript need improvement.
3. Reconsider after major revisions. The article has some merit in, but it fails to meet the all requirements
for publication as scientific paper. The manuscript needs a serios improvement in order to be accepted.
Reviewers should clearly and specifically mention areas were the manuscript need improvement and, if
possible, provide references to substantiate the comments made.
4. Reject. The article has serious flaws, makes no original contribution, has inadequate research design, has
not enough experimental date to draw de conclusions or data doesn’t scientifically sound or are not
robust enough, the conclusions are not supported by the results. The manuscript was not prepared and
presented according with guide for authors.
2. Major drawback
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