VAN DOAN, BUI VAN DAN, NGUYEN HOANG ANH: Comparasion of 3 imputation methods for identifying drugs-induced Stevens-Johnson syndrome and toxic epidermal necrolysis by retrospective anal[r]
(1)(2)TAP CHI DITOC HOC ISSN 0866 - 7861 6/2017 (So 494 NAM 57)
MUC LUC NGHIEN CLPU - K Y THUAT
MAI N G U Y E N N G O C T R A C , N G U Y E N P H U O N G D U N G , DO TH! H O N G TOOL Khuyen cao ve nghien cuu tiromg tac thuoc in vitro va in
vivo qua trinh phat then thuoc mai
N G U Y E N K H A C DONG, T R A N T H U THUY, O A O T H U T R A N G ,
NGUYEN VAN DOAN BUI VAN DAN, NGUYEN HOANG ANH: SO sanh phirang phap quy ket hoi chiing Stevens-Johnson va hoai tu-thuwig bi nhiem doc gay bdi thuoc co so dO lieu bao cao
ADR cua Viet Nam PHAM VAN TAT, VAN TH| MY HUE: Thiet ke va doan hoat tinh
gay doc t§ bao ung thu- bieu mo ciia dan chat 2-arylquinazolin-4-on so
dung mo hinh QSAR 11 NGUYEN TH! CAM VI, TRiNH QUYNH DIEU, TRAN PHI HOANG YEN,
THAI KHAC MINH, TRAN THANH OAO: Khao sat kha nang chong oxi hoa va cai thien tri nho ngSn han cua dan chat benzylaminochalcon
tren chupt nhAt 17 L£ KHAC TUAN, PHAM OiNH DUY: Dieu che gia mang lipid cau true
nano chua miconazol nitrat blng phoong phap vi nhu toong 21 NGUYEN TH! KIM THU MAC DiNH HUNG: Tong hop
p-methan-3,8-diol va thi> nghiem hoat tinh xua mu6i 26 VO BiNH DUONG, NGUYEN XUAN TRUNG, NGO XUAN TRiNH,
PHAM VAN HlEN, NG6 TH| TUYET MAI: Nghien cou djnh logng mangiferin tri mau {Rhizoma Anemarrhenae) bdng sSc ky long
hieu nang cao 29 TRAN HUU GlAP, HA TH! THOA, CAO TH! HUE, NGUYEN TH| TU
OANH, VG TH! KIM OANH, NGUYEN TH! MINH HANG, NGUYEN VAN HUNG, NATALIA S MISHCHENKO, SERGEI A FEDOREEV, LE NGUYEN THANH: Hpp chat flavan va acid beo phan lap to vo than
cay mau cho trai day (Knema pachycarpa de Wilde) 33 NGUYEN THj LAR PHAM THj NGUYET HANG: Nghien cii-u
tac dung oc ch§ so ti'ch tu lipid gay boi acid oleic cua cao chiet to Ganoderma sp\ tang ky sinh va dai hoa te tan tren te
bao HepG2 36 TRAN LE HANG, NGUYEN NHAT LAM, LY MINH HUY, LE NGUYEN
BAO KHANH, TRUONG NGOC TUYEN: Tong hop dan chit halogen
cua acid anthranilic bang phoong phap su dung Oxone® 40 LE TUAN, NGO HONG THAI NGUYEN DINH NGA, HUYNH TH!
NGQC PHUONG: Tong hpp va thu* hoat tinh khang nam cua mot so din chit ((2-benzoylhydrazono) methyl) pyridinium va
((2-pheny-Ihydrazono) methyl) pyridinium 43 VO TH! KIM THU, NGUYEN TH! THAO TRAN, DOAN NGOC NHUAN,
LE NGOC THACH: Thanh phan hoa hoc va mot so hoat tinh sinh hoc
cua tinh dau la 6i Dai Loan 48 NGUYEN THj THU TRANG, 00 THj THUY, PHAM NGOC TUAN ANH:
Tong hpp va danh gia hoat tinh khang khuln cua cac dan chit mdi
salicyloylbenzofuran 51 NGUYEN VAN RU: Tao che phlm insulin pegyl hoa va danh gia mot
so dac tinh cua che phlm de dung y doge 55 NGUYEN TH! KIM THU, BUI THANH TUNG: Oanh gia kha nang Crc
che enzym acetylcholinesterase cua cac phan doan dich chiet bim bim
trlng (Convolvulus pluricaulis Choisy) 59
TRAN ANH VO, DUONG TH! MONG NGOC, NGUYEN TH! THU HANG: Xay dung tieu chuan cho dupe lieu kho qua loai qua nho
(Momordica charantia L var. abreviata Sen) 63
N G U Y E N TH! MAI: Adenosin va hai hpp chit lignan phan lap tu phan
tren mat dlt cua cay gle - Momordica cochinchinensis (Lour.) Spreng 67
N G U Y E N TH! THANH D U Y E N , D A M THANH X U A N : Nghien cuu bao
mang khang dph vi cho pellet pantoprazol 71 NGUYEN VAN LINH, D U ONG TH| HAl YEN, HOANG LE TUAN ANH,
VO MANH HUNG, PHAM THANH KY: Hai hpp chit phenolic glycosid phan lap tu phln tren mat dlt cay tien hac thao (Agrimonia pilosa
Ledeb var. pilosa) 76
TRAN TR|NH CONG, DAM THU HlEN: Nghien cuu he vi nlm tren vj thuoc kha tu (Fmctus Terminaliae) dang luu hanh o mot so hieu thuoc
Dong dupe tren dja ban Ha Npi 78
PHARMACEUTICAL JOURNAL ISSN 0866 - 7861
6/2017 (N° 494 Vol 57) CONTENTS R E S E A R C H - T E C H N I Q U E S
MAI NGUYEN NGOC TRAC, NGUYEN PHUONG DUNG, 00 TH| HONG TU'OI: Recommendations on the in vitro and in vivo research of
drug interaction in development of novel drugs
N G U Y E N K H A C D G N G T R A N T H U T H U Y D A O T H U T R A N G N G U Y E N
VAN DOAN, BUI VAN DAN, NGUYEN HOANG ANH: Comparasion of imputation methods for identifying drugs-induced Stevens-Johnson syndrome and toxic epidermal necrolysis by retrospective analysis of the relevant data from the national pharmacovigilance database in Vietnam PHAM VAN TAT, VAN TH| MY HUE: Structural design and cytotoxic
prediction of new 2-aryl-quinazolin-4-one derivatives against the KB
cell line using QSAR model 11 NGUYEN TH| CAM VI, TRiNH QUYNH DIEU TRAN PHI HOANG
YEN, THAI KHAC MINH, TRAN THANH DAO: Experimental antioxidant and memory-improving property of benzylaminochalcon in
mice 17 LE KHAC TUAN, PHAM O'lNH DUY: Preparation of miconazole nitrate
loaded nanostructured lipid carriers by microemulsion 21 NGUYEN TH! KIM THU, MAC DiNH HUNG: Synthesis and culicifuging
activity of p-methane-3,8-diol 26 VG BiNH DUQNG, NGUYEN XUAN TRUNG, NGO XUAN
TRiNH PHAM VAN HlEN, NGO THj TUYET MAI: An HPLC procedure for quantitative analysis of mangiferin in Rhizoma
Anemarrhenae 29
TRAN HUU GlAP, HA TH! THOA, CAO THI HUE, NGUYEN THI TU OANH, VU THj KIM OANH, NGUYEN TH! MINH HANG, NGUYEN VAN HUNG, NATALIA S MISHCHENKO, SERGEI A FEDOREEV, LE NGUYEN THANH: Flavans and fatty acids isolated from the stem
barks of Knema pachycarpa (de Wilde) 33
NGUYEN TH! LAP, PHAM THj NGUYET HANG: Inhibitory activity of the ethanol extracts from Ganoderma sp\ Scurrula parasitica (L Merr and Asarum maximum (Hemsl.) on the lipid accumulation in the
HepG2 cell line 36 TRAN LE HANG, NGUYEN NHAT LAM, LY MINH HUY, LE NGUYEN
BAO KHANH, TRUO'NG NGQC TUYEN: Synthesis of some halogen
derivatives from anthranilic acid and Oxone® 40 LE TUAN, NGO HONG THAI NGUYEN OINH NGA, HUYNH TH|
NGOC PHUO'NG: Synthesis and evaluation of antifungal activity of some derivatives of ((2-benzoylhydrazono) methyl) pyridinium and
((2-phenylhydrazono) methyl) pyridinium 43 VO TH! KIM THU, NGUYEN TH! THAO TRAN, DOAN NGOC NHUAN,
LE NGOC THACH: Phytochemical composition and some bioactivities of
the leaf oils of the plant Taiwan guava (Psidium guajava L.) 48 NGUYEN TH! THU TRANG, DO THj THUY, PHAM NGOC TUAN ANH:
Synthesis and antibacterial activities of novel 2-salicyloylbenzofuran
derivatives 51 NGUYEN VAN RU: Preparation and characterization of PEGyl insulin by
covalent conjugation with methoxy polyethylene glycol aldehyd (mPEG-CHO) 55 NGUYEN TH! KIM THU, BUI THANH TUNG: Acetylcholinesterase
inhibitory activity of various fractions of extracts from Convolvulus
pluricaulis Choisy 59
TRAN ANH VO, DUONG TH! MONG NGOC NGUYEN TH! THU HANG: Establishment of the quality control standards for the fruits of
Momordica charantia L var. abreviata Ser 63
NGUYEN TH! MAI: Isolation of adenosine and two lignan compounds
from the aerial parts of Momordica cochinchinensis (Lour.) Spreng 67 NGUYEN TH! THANH DUYEN, DAM THANH XUAN: Formulation of
film coated pellets for enteric delayed release capsules of pantoprazole 71 NGUYEN VAN LINH, DUONG TH! HAl YEN, HOANG LE TUAN ANH, VU MANH HUNG, PHAM THANH KY: Isolation and identification of two phenolic glycosides from the aerial parts of Agrimonia pilosa
Ledeb var. pilosa 76
TRAN TR|NH CONG DAM THU HlEN: Fungal contamination of the herbal item Fructus Terminaliae curremtly circulated in traditional
(3)• Nghien cu»u - Ky thuat
interaction studies: Regulatory guidance and an industry and labeling recommendations, February
Perspective", The AAPS Journal, 15(3), 629-645 V p h n g N g u y^n ^ c s ( Q ) ^ p h^p c n g
11 ^ D e p a r t m e n t of Health and Human Services (2012^ h § t h t j n h t k § d a n v^ ^ S j S t „a n- B^0 ^ „6 /
Food and drug administration, Center for Drug Evaluation and 7., „ ,j n A ~ w - r
Research (CDER)", Guidance for industry, drug interaction ^ P° X ' ^ ' ^ Q C ^ P'
studies-study design, data analysis, implications for dosing, H ° Chi Minh
(Ngay nhan bai: 09/12/2016 - Ngay phan bien: 08/03/2017- Ngay duyet dang: 02/06/2017)
r
So sanh phirong phap quy ket hoi chung Stevens-Johnson
mt r
va hoai tu* thirong bi nhiem doc gay bdi thuoc trong co* so* dfr lieu bao cao ADR cua Viet Nam
Nguyen Khac Dung1 % Tran Thu Thiiy1, Dao Thu Trang1
Nguyen Van Doan3, Bui Van Dan3, Nguy en Hoang Anh1*
'Trung tarn Quae gia ve Thong tin thuoc vd Theo cloi phan irng co hai cua thuoc, Tnrang Dai hoc Dugc Ha Not •'Trung tarn Cdnh gidc Dugc khu vuc Midi-Pyrenees, Toulouse, Phdp
'Trung tarn Di irng vd Mien dich him sang, Benh vien Bach Mai 'E-mail: anh90tk@yahoo.com
Summary
In view that though Stevens-Johnson's syndrome and Toxic epidermal necrolysis (SJS/TEN) are serious ADR with high mortality rate is high (up to 25%), the imputability methods for these reactions seemed not so reliable, and occasionally, the clinical expert judgements in some specific cases were quite different; and from 174 reports on severe muco-cutaneous reactions SJS/TEN in national database of pharmacovigilance in the period 2006-2013, 355 ADR-drug pairs were identified, a new imputability method (ADLEN) specified for SJS/TEN (ALDEN) was investigated in comparison with the former WHO and Najanro's methods, to estimate the corresponding causality relationship and calculate the correlation A low correlation was revealed between ADLEN method and WHO and Najanro's methods for the 174 cases in question (0.38 and 0.23, respectively) For estimating SJS/TEN reactions, in comparison with ALDEN method, the specificity of WHO method was low (Sp=36%) and Najanro's method was even absolutely nonspecific (Sp=0%) This suggested the ALDEN method should serve as a powerful tool for assessment of the causalities of drug-induced SJS/TEN not only in pharmacovigilance imputation but also in clinical practice
K e y w o r d s : ALDEN, Pharmacovigilance database, SJS/TEN, Naranjo, WHO method
Dat van de ti> vong trung binh cua loai phan u n g len tdi Hoi Chung Stevens-Johnson va hoai t u t h u g n g - % '2 « Viec chl ro chinh xac nguyen nhan SJS/
bi nhidm doc (SJS/TEN) la n h u n g phan u n g tren da T E N 9i C |P b a c s T d i a u t r! r a d!n h k! P t h > i v a v iPc
nghiem trong, d u g c dac t r u n g b d i ti le t u vong cao va n g u n g s u dung thuoc nghi n g d la nguyen nhan
thuoc d u g c cho la nguyen nhan chinh gay hoi c h u n g k h i d d v i n d uYt r i t i aP t Mc n h Q , n9 t h u°c d i a u t r! c a n t h i a t
nay ^ N h u n g n a m gan day, Trung tarn Q u o c gia ve k h a c- d a c b i a t l a t r o n9 9'f' d o a n Ph a t c d a Ph a n
Thong tin thuoc va T h e o ddi phan u n g co hai cua thuoc urig Tuy nhien, viec chan d o a n nguyen nhan S J S / (Trung tarn D I & A D R Q u o c gia) nhan d u g c n h i i u bao T E N t h u c hanh gap nhieu khd khan nhan cao t u nguyen lien q u a n tdi loai phan u n g (nam vien y te s u dung p h u o n g phap chung cho tat ca cac 2013 ghi nhan bao cao) Viec quy ket chinh xac moi loai phan u n g nhir p h i r o n g phap quy ket nhan qua quan he nhan qua g i u a thuoc nghi n g d va SJS/TEN cua To c h u c Y te the gidi (thang W H O ) hay thang cua gap nhieu t r d ngai d o benh nhan nhieu bao cao Naranjo de d a n h gia loai phan u n g Vi vay, nghien co x u h u d n g si> dung nhieu thuoc dong thdi (dac biet c u u d o g e tien hanh v o i muc tieu: so sanh m u c d o la cac benh nhan cao tuoi) va ban chat cua SJS/TEN la t u o n g dong giua p h u o n g phap A L D E N (Algorithm for
phan u n g qua man m u g n (thdi gian tiem tang Kr luc bat Assessment of Drug Causality in Epidermal Necrolysis
dau s u dung thuoc tdi luc xuat hien phan u n g dac trung - thang chuyen biet danh gia hoi c h u n g S J S / T E N ) v d i d a o dong mot khoang thdi gian dai t u vai tdi p h u o n g phap cua W H O va cua Naranjo quy ket vai t u n )w. SJS/TEN can phai nhan d u g c s u quan tarn moi quan he nhan qua phan u n g tren da nghiem trgng dac biet danh gia Igi ich/nguy c o cua thuoc d o ti le gay bdi thuoc
(4)• Nghien ci>u - Ky thuat
D o i t u ' g n g v a p h u o n g p h a p n g h i e n c u u Doi t u o r i g nghien CLFU
Toan bo bao cao v§ phan u n g tren da nghiem trong C o s o d o lieu (CSDL) bao cao t u nguyen l u u t r u tai Trung tarn D I & A D R Q u o c gia giai doan t u 01/2006 tdi 12/2013
Tieu c h u a n l y a c h o n
Bao cao v d i thuat n g u d u g c mo ta ve S J S / T E N d u g c sang loc C S D L vdi cac thuat n g u mo ta bao gom: "hoi c h u n g Stevens-Johnson", "hoi c h u n g Lyell" hay "hoai ti> t h u g n g bi nhiem doc", hoac bao cao m o ta ton t h u o n g da kieu trot loet /tuot da t u n g mang tren % dien tich c o the hoac loet hoc t o nhien kern ton t h u o n g ngoai da kieu trot loet tren da/mun bong n u d e
Tieu c h u a n loai trip
B a o c a o thieu t h o n g tin v e m o ta p h a n u n g , k h d n g g h i / k h d n g xac dinh d u g c t h u o c nghi n g d , thidu t h o n g tin n g a y bdt dau dieu tri hoac xuat hien p h a n u n g
P h u o n g phap nghien cu»u
D a n h gia moi quan he nhan qua g i u a thuoc nghi n g d d u a tren hoi c u u C S D L bao cao A D R t u nguyen Danh sach cac thuoc nghi n g d va ket qua tham dinh cuoi cung cua chuyen gia theo thang W H O d u g c tn'ch xuat d u a tren bao cao goc luu t r u tai Trung tarn Bao cao A D R goc lien quan d u g c tiep tuc d a n h gia moi quan he nhan qua g i u a thuoc nghi n g d va S J S / T E N theo p h u o n g phap A L D E N va Naranjo Viec danh gia d u g c t h u c hien bdi n h o m nghien c u u c d bac sT lam sang chuyen nganh Di u n g - M i i n dich lam sang T h a n g A L D E N d u g c dinh nghTa la thuat toan chuyen d e d a n h gia cac phan u n g tren da nghiem n h u S J S / T E N d u a tren bo tieu chi: thdi gian tiem tang, s u c d mat cua thudc c o the v a o xuat hien phan u n g , s u n g u n g dung thuoc, tien s u xay phan u n g v d i thuoc hoac phan u n g tai dien tai s u dung thuoc, m u c nguy c o cua thuoc va yeu to benh nguyen khac (bang 1)[ 3-5
Tong diem thu d u g c t u ket qua sau danh gia tieu chi se d u g c quy doi t u o n g u n g v d i mot m u c quy ket thuoc-ADR (bang 2)
Bang 1. Thang danh gia ALDEN danh gia phan (mg SJS/TEN151
Tieu chi Cho diem Quy tac ap dung
Thai gian tiem tang:
Thai gian tir bat dau diing thudc den xuat hien phan ung
Rat co kha nang: +3 Tir den 28 CcKh3 nariij +2 Tir 29 den 56
Cd the: +1 Tir den
Khdng chac chan: -1 Tren 56
Loai tn>: -3 Thuoc dirac bat dau sir dung vao hoac sau xuat hien phan dng Neu trirdc day benh nhan da tang cd phan irng vdi thuoc nay:
Rat cd kha nang: Cd the:
+3 Tu-1 cen +1 Ti> den 56
Sir cd mat cua thuoc ca the vao xuat hien phan ung
Chac chan:
Nghi ngd:
Loai tru:
+0
-3
Thuoc dirge tiep tuc sir dung cho den xuat hien phan ung hoac da dirge ngirng trade xult hien phan dng it han nam Ian thdi gian ban thai
Thuoc da dirge ngirng trirdc xuat hien phan Lrng nhidu han nam Idn thdi gian ban thai Nghi ngd xay tirang tac thuoc hoac thay doi chdc nang gan than lam anh hirdng tdi nong cua thuoc ca the
Thuoc da dugc ngirng trirdc xuat hien phan dng nhieu han nam Ian thdi gian ban thai Khdng nghi ngd xay tirang tac thudc, chirc nang gan than khdng thay doi
Sir ngirng sir dung thuoc
Trung tinh: +0 Ngirng dung thudc hoac khdng rd
Am tinh: -2 Thuoc tiep tuc dirge dung ma phan dng cai thien hoac khdng xay phan ung
Da tdng xay phan ung vdi thuoc hoac phan ung tai dien tai sir dung thuoc
Xdp hang cua thuoc theo nguy ca xay ra phan ung
Daang tinh dac hieu doi vdi
benh va thuoc: +4 SJS/TEN xay dung chinh thuoc Dirang tinh dac hieu ddi vdi
benh hoac thuoc: +
SJS/TEN xay dung thudc taang tg hoac phan ung khac tirang tg xay dung chinh thuoc
Dirong tinh khdng dac hieu: +1 Phan ung khac tirang tg xay sau dung thudc tirang tg Khdng lam/ Khdng rd: +0 Khdng biet tien sir dung thuoc nay/ Khdng dung lai thuoc
Am tinh: -2 Pa dung thuoc ma khdng xay phan irng/ Dung lai thuoc ma khdng xay phan dng Rat lien quan: +3 Thudc thudc danh sach "nguy cacao"
Lien quan: +2 Thuoc thudc danh sach "nguy ca co y nghia"
Thuoc thudc danh sach "chira danh gia duoc nguy co/ hoac da cd ghi nhan xay phan dng vdi thudc theo ket qua mot vai bai bao, bao cao dich t§
Nghi ngd: +1
Khdng nghi ngd: Thuoc thudc danh sach "khdng cd nguy co/
Khdng rd: +0 Cac thudc khac (bao gom ca nhCrng thuoc mdi liru hanh va thuoc gay nhieu) Oiem trung gian = Tong diem tdt ca cac tieu chi tren
Nguyen khac
nhan
Cd the: Trong mot ca bao cao, neu cd it nhat mot thuoc cd diem trung gian > thi trir mot diem tir diem trung gian cua cac thuoc cd diem trung gian <
Tong diem : -12 den 10
(5)• Nghien C C P U - Ky thuat
Bang 2. Bang quy ddi diim- mire danh gia cua thang ALDEN
Tong diem Mux; danh gia Quy uuc mire danh gia
>6 Rat co kha nang
4 - Co kha nang
2 - Co the
0 - Khong chdc chan
<0 Rat khong chac chan
Ket qua tham dinh d u g c phan loai m d c vdi s u t u u n g dong thuat ngO quy ket g i u a thang A L D E N , W H O va Naranjo (bang 3)
Bang 3. Quy ket muc danh gia va gia tri chan doan cua cac phuung phap
Mipcquyket ALDEN NARANJO WHO Gia tri chan doan
Rat co kha nang Chac chan Chac chan
Co kha nang Co the
Co kha nang Co the
Co kha nang Dirong tinh (ADR) Co the
Khong chac chan
Rk khong chdc chdn Khong chdc
Khong chac chan
Chaa phan loai Am tinh (Khong ADR) Khong the phan loai
Ket qua thu d u u c d u p e x u ly va phan tich bang phan m e m thong ke R (phien ban 3.3.1) Moi t u u n g quan giua p h u o n g phap d u p e tinh toan theo p h u o n g phap S p e a r m a n thong qua gia tri rho va gia tri p t u u n g u n g cua cac cap p h u o n g phap He so t u u n g quan rho the hien s u t u o n g dong cua cac p h u o n g phap danh gia doi vdi phan u n g tren da nghiem trpng n h u SJS/TEN Gia tri chan doan cua thang W H O , thang Naranjo va thang A L D E N d u p e xac dinh thong qua cac chi so dp dac hieu, dp nhay, gia tri d u doan d u o n g tinh, gia tri d u doan a m tinh t u o n g u n g
Ket qua nghien cu u
Trong C S D L bao cao A D R t u nguyen giai doan 2006-2013, co 174 bao cao A D R ve SJS/TEN thoa m a n tieu chi l u a chpn va loai t r u , t u o n g u n g vdi 355 cap quy k§t thuoc nghi n g d - A D R Trong 355 cap thuoc-ADR nay, thuoc khang sinh xuat hien nhieu nhat v d i 75 t r u d n g h p p (22,1%), tiep la thuoc giam dau, sot, chdng viem vdi 55 t r u d n g h p p (16,2%), thuoc h u d n g tarn than t r u d n g h p p (13,3%), thudc chong lao 41 t r u d n g h p p (12,1%), thuoc tri gut 20 t r u d n g h p p (5,9%), thuoc co nguon goc d u p e lieu/thuoc y hoc co truyen 14 t r u d n g h p p (4,1%) va cac nhom thuoc lai xuat hien v d i ti le nho (0,3-3,2%) Paracetamol la thuoc d u p e ghi nhan nhieu nhat vdi 38 bao cao, tiep la carbamazepin (26 bao cao), cotrimoxazol (15 bao cao) va allopurinol (12 bao cao) (bang 4) Trong 355 cap quy ket thuoc-ADR, ket qua danh gia moi quan he nhan qua c d s u khac biet dang ke giua p h u o n g phap (hinh 1) So cap quy ket thu6c-ADR s u dung thang A L D E N co quy ket m u c va thap h o n so vdi thang W H O , m u c va lai thap h o n so v d i thang W H O Khi s u dung thang Naranjo, khong co cap quy ket thuoc-A D R d m u c va m u c m u c quy ket phan Ion la mu'C (87%) Ve moi t u o n g quan cua giQ'a ket qua tham dinh bao cao S J S / T E N theo thang A L D E N so vdi W H O va Naranjo kha thap v d i gia tri rho bdng 0,38 va 0,23 t u o n g u n g (hinh 2) D p nhay cua thang Naranjo
t u o n g d u o n g vdi A L D E N nhien hoan toan khong dac hieu danh gia loai phan u n g D p nhay cua W H O so v d i A L D E N d m u c t u o n g d6i nhien dp dac hieu van thap (Sp = % ) (bang 5)
Bang 4. Cac thuoc nghi ngd cac bao cao SJS/TEN (tin suit>1)
Hoatchat So bao cao (%)
N=174 Hoaf chat
So bao cao (%) N= 174 Paracetamol 38 (21,8%) Levomepromazin 3(1,7%) Carbamazepin 26(14,9%) Piracetam 3(1,7%) Cotrimoxazol 16 (9,2%) Serratiopeptidase 3(1,7%) Thuoc nguon g6c
duvc lieu 14(8%) Chymotrypsin 2(1,1%) Allopurinol 12(6,9%) Azithromycin 2(1,1%) Isoniazid (5,2%) Cefadroxil 2(1,1%) Colchicin (4,6%) Chlorpheniramin 2(1,1%) Pyrazinamid (4,6%) Doxycycl - 2(1,1%) Rifampicin (4,6%) Erythromycin 2(1,1%) Amoxicillin 7(4%) Gabapentin 2(1,1%) Ethambutol 7(4%) Glucosamin 2(1,1%) Streptomycin (4%) Multivitamin 2(1,1%) Ciprofloxacin (3,4%) Nevirapin 2(1,1%) Cefuroxim (2,9%) Nifedipin 2(1,1%) Meloxicam (2,9%) Penicillin 2(1,1%) Acid clavulanic (2,3%) Phenobarbital 2(1,1%) Ampicillin (2,3%) Piroxicam 2(1,1%) Ofloxacin (2,3%) Prednisolon 2(1,1%) Vitamin 3B (2,3%) Promethazin 2(1,1%) Cefixim 3(1,7%) Roxythromycin 2(1,1%) Cefotaxim 3(1,7%) Spiramycin 2(1,1%) Cephalexin 3(1,7%) Sulbactam 2(1,1%) Chloramphenicol 3(1,7%) Vitamin C 2(1,1%) Chlorpromazin 3(1,7%) Vitamin PP 2(1,1%)
(6)• Nghien cu>u - Ky thuat
300
Hinh 1. Tile mire quy ket thuoc-ADR thim dinh theo thang
B
4' 1#
•
• » NARANJO 3 WHO
rho= 0.23
VAHOM
4
rtio= 0.38
ALDEN
2
1 u ; ?
• •
••• 1 2 1 4
ALDEN Uechod
1 J ALDEN Method
4
Hinh A - Muc tuung quan giira phuung phap Naranjo so vdi phuung phap ALDEN;
B - Muc tuung quan giue phuung phap WHO so vdi phuung phap ALDEN
Bang 5. Muc tuung quan va gia tri chin doan cua thang WHO va Naranjo so vdi ALDEN
Gia tri chan doan cua cap
phuwng phap WHO-ALDEN Naranjo-ALDEN
Do nhay Se 85,8% 100%
Do dac hieu Sp 36,2% 0,0%
Gia trj da doan daong tinh 59,2 % 51,6% Gia tri da doan am tinh 70,2 % 100% He so taong quan Spearman [rho) 0,38 0,23
Gia tri p < 0,0001 < 0,0001
Ban luan
T u n a m 1976, tren the gidi da co nhieu h u d n g tiep can quy ket moi quan he nhan qua thuoc-A D R , chu yeu d i r g e chia nhom Idn: y kien cua chuyen gia d u a theo tieu chi lam sang, ti§p can theo xac suat va thuat toan M Quyet dinh cua chuyen gia hoac nhan vien y te d u a tren tieu chi lam sang t h u d n g
d u g c ap dung t h u c hanh t h u d n g quy Tuy nhien, y kien cua chuyen gia d mot goc nao d o tiem an nhieu khiem khuyet n h u m a n g d a m tinh chu quan va thieu s u chuan h o a[ ) Dieu co x u h u d n g dan tdi lap
lai t h l p d a n h gia moi lien q u a n thuoc-ADR H o n n u a , tien trinh d u a quyet dinh cua chuyen gia t h u d n g khong d u g c dien giai ro rang, vi the thieu "minh bach" va khong "bdt c h u d c " d u g c [ ] B e n canh do, h u d n g
tiep can xac xuat la hien g a p nhieu kho khan viec ap dung t h u c hanh t h u d n g quy c i n phai d u a theo phan phoi mau ve xac suat Vi vay, p h u o n g phap s u dung thuat toan d u d n g n h u la mot p h u o n g an de dang ap dung nhat t h u c hanh v d i viec cho diem cac tieu c h i va d a n h gia d u a vao ket qua tong diem thu d u g c Khi s u dung thuat toan kieu n h u A L D E N hay Naranjo, s u dong thuan cua cac Ian d a n h gia khac cua cung mot n g u d i d a n h gia hoac g i u a cac n g u d i danh gia khac t u o n g doi cao, nhien ket qua phu thuoc chu yeu vao so d u g c gan cho moi tieu chi, day chinh la yeu to d u a tren kinh nghiem
(7)• Nghien cCru - Ky thuat
Hinh 1. Vie muc quy kit thuoc-ADR thim dinh theo thang
•
4
3 NARAHJO
rfio= 0.23 z
ALDEN o
2
WHO
rho= 0.38 ALDEN
Hinh A - Muc dp tuung quan giua phuung phap Naranjo so v&i phuung phap ALDEN; B - Muc tuung quan giua phuung phap WHO so voi phuung phap ALDEN
Bang 5. Muc tuung quan va gia tri chin doan cua thang WHO va Naranjo so v&i ALDEN
Gia tri chan doan cua cap
phuwg phap WHO-ALDEN Naranjo-ALDEN
06 nhay Se 85,8% 100%
Do (Jac hieu Sp 36,2% 0,0%
Gia tri da doan daong tinh 59,2 % 51,6% Gia tri da doan am tinh 70,2 % 100% He s6 taang quan Spearman (rho) 0,38 0,23
Gia tri p < 0,0001 < 0,0001
Ban luan
T u n a m 1976, tren the gidi da co nhieu h u d n g tiep can quy ket moi quan he nhan qua thuoc-ADR, chu yeu d u g c chia nhom Idn: y kien cua chuyen gia d y a theo tieu chi lam sang, tiep can theo xac suat va thuat toan 16-91 Quyet dinh cua chuyen gia
hoac nhan vien y te d y a tren tieu chi lam sang t h u d n g
d i r g e ap dung t h y c hanh t h i r d n g quy Tuy nhien, y kien cua chuyen gia d mot goc nao tiem an nhieu khiem khuyet nhir m a n g d a m tinh chu quan va thieu s y chuan h o a[ Dieu cd xu h i r d n g dan tdi lap
lai thap danh gia moi lien quan thu6c-ADR H u n n u a , tien trinh dira quyet dinh cua chuyen gia t h i r d n g khong d i r g e dien giai ro rang, vi th§ thieu "minh bach" va khong "bat c h i r d c " d i r g e [ ) Ben canh do, h i r d n g
tiep can xac xuat la hien g a p nhidu kho khan viec ap dung t h u c hanh t h u d n g quy can phai d u a theo phan phoi m i u ve xac suat Vi vay, p h u u n g phap sir dung thuat toan d u d n g n h u la mot p h u u n g an d§ dang ap dung nhat t h u c hanh v d i viec cho diem cac tieu c h i va danh gia d u a vao ket qua tong diem thu d u g c Khi s u dung thuat toan kieu n h u A L D E N hay Naranjo, s u dong thuan cua cac Ian danh gia khac cua cung mot n g u d i danh gia hoac g i u a cac n g u d i danh gia khac t u u n g doi cao, nhien ket qua phu thugc chu y§u vao so d u g c gan cho m6i tieu chi, day chinh la yeu to d u a tren kinh nghiem
(8)• Nghien C C F U - Ky thuat
chuyen m d n Cac p h u u n g phap loai co the ap dung rang rai (muc dich d e danh gia tat ca cac A D R va tat ca cac thuoc) hoac cu the t u n g t r u d n g h u p (tire la a p dung cho A D R cu the va thuoc lien quan t u u n g u n g )
Trong nghien c y u nay, nhom nghien c i m da b u u c dau ap dung thang A L D E N de danh gia phan irng SJS/ T E N C S D L bao cao A D R n h a m v u i muc dich so sanh mi>c t u u n g dong v u i cac p h u u n g phap chung khac Naranjo mac du la p h u u n g phap d u u c ky vgng la mot cdng cu nhay ben de phat hien cac tin hieu canh giac d u u c (khach quan, lap lai cao), nhien thang lai hoan toan khong phu h u p de danh gia SJS/ T E N d o dac hieu cua Naranjo so vui A L D E N bbng T r u u c do, nghien ciru cua Nguyen Thj T h u Thuy va C S n a m 2011 ("So sanh tham dinh moi q u a n he nhan qua phan u n g co hai cua thuoc bao cao t y nguyen ve Trung tarn D I & A D R Q u o c gia b l n g p h u u n g phap cua Naranjo va p h u u n g phap cua To c h d c Y te the giui",
Khoa luan tot nghiep Ducrc sy, Tru&ng Dai hoc Duac Ha Noi) tren bao cao A D R cua Viet N a m (n = 100) cho rdng thang Naranjo va W H O kha t u u n g dong d a n h gia cac bao cao A D R (K =0,52) Tuy nhien ap dung d6i v u i cac bao cao SJS/TEN thl thang W H O co dac hieu cao h u n so v u i Naranjo danh gia cac bao cao S J S / T E N , n h i m g thang Naranjo lai d y doan cac bao cao "khong A D R " tot h u n s u v u i thang W H O (do nhay Se = 100%) Doi v u i danh gia ve phan u n g ngoai da nghiem trong, rd rang la It co s y t u u n g dong g i u a W H O va A L D E N va gan nhir khong co s y t u u n g dong giua thang Naranjo va thang A L D E N Do sir khac c l u true, tieu chuan quy ket va each l i r y n g gia tieu chuan co s y khac biet giCra cac loai phan ting co hai, viec ap dung thang chuyen biet nhir A L D E N se co y nghTa rat Ion t h y c hanh lam sang vi thang d i r y c cong nhan la cb the xac dinh chinh xac thudc gay SJS/TEN va khong can n g t i n g dieu tri vui cac thuoc dieu tri k h a c[ ]
S y khac biet lun nhat cua thang W H O v u i A L D E N tap trung u moi lien he ve mat thui gian (thai gian tiem tang cua SJS/TEN t h u d n g tir tai 28 ngay), dieu gay nhieu doi va gay anh h u d n g tui y kien danh gia chu quan cua chuyen gia l ) Ben canh do, ydu to tai
sir dung thudc khdng d i r y c phep ap dung mire nghiem cua A D R d i n tui it mire quy ket m i r e " c h i c c h i n " ddi vui cac bao cao dung thang W H O S y khac biet lun n h i t giCra thang Naranjo so v u i A L D E N la khdng loai trir d i r y c cac yeu to gay nhieu nhir benh m i c kern, thuoc sir dung dong thui, ngirng thuoc cting luc vui tat cac cac dieu tri dong thui hoac ngirng thuoc m a khdng c d tien then Do ban chat dac thu cua S J S / T E N bao g o m tap h y p cua nhieu trieu c h u n g dac hieu va khdng dac hieu, viec phat hien va phan biet vui cac A D R khac cung dat thach thirc doi v u i n g i r u i bao cao cung nhir chuyen gia tham dinh Dieu c d
the giai thich s y khdng dac hieu ap dung cac thang khdng chuyen biet d a n h gia q u a n he nhan qua cua cac bao cao S J S / T E N
Ket luan
D a y la nghien ciru ddu tien v a n dung thang A L D E N de danh gia cac bao cao S J S / T E N C S D L bao cao A D R cua Viet N a m Nghien ci>u cung chi thang W H O va thang Naranjo c d m i r e t i r u n g dong kha thap so sanh v u i thang A L D E N d a n h gia cac bao cao lien quan tui loai phan ting D o dac hieu cua thang W H O kha thap va thang Najanro hoan toan khdng dac hieu d a n h gia moi quan he nhan qua S J S / T E N gay bui thuoc so sanh v u i thang A L D E N Nghien c u u da bo sung mot p h i r u n g phap mtii chuyen biet h u n de danh gia cac phan ting tren da nghiem trgng nhir SJS/ T E N he thong cac p h i r u n g phap tham dinh A D R hien tai u Viet N a m va h i r u n g den viec can nhac ap dung A L D E N t h y c hanh canh giac d i r y c cung nhir t h y c hanh lam sang
Tai lieu tham khao
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{Ngay nhan bai: 28/12/2016 - Ngay phan bien: 22/03/2017 - Ngay duyet dang: 02/06/2017)