benh nhan da chUng minh kha ning tang^toc eua qua trinh vet thUdng so vdi nhdm ehCftig bang cac xet nghiem vi khuan, te bao hoe va hinh thai hoc. Laser Doppler flowmetry thay sU cai thien dang ke cac vi tuan hoan trong khu vuc vet thuong. PhUdng phap nay giup td chUc hat mpc nhanh va giam 3 den 5 ngay thay bing de ddng vet thUdng [5].
Shulutko (2004) trong mdt nghien eUu khdng co nhdm chUng vdi 65 benh nhan tieu dudng cd ton thuong hoai ti!f d chan dieu tri vdi plasma ndng dp NO tao ra cao hd trp vet thUdng nhanh lanh [61.
Vi sinh v i t sdng tren be mat da ed the gay nen eac benh khac" nhau trong dd cd viem da di Ung.
Daesehlein va ddng nghiep (2009) da dieu tri mdt benh nhin cd tu cau vang ky sinh tren da trong thdi gian 3 phut bang plasma lanh vdi ap sua't (1-5 kV, 1,5 MHz, khi argon) ket qua tieu diet chpn Ipc dong tu cau vang [7]- . . -. ' - Mertens (2009) cung chung minh mpt giam so lUdng tu cau vang xudng mUdi lan trong vong 30 ngay d canh tay ciJa benh nhin viem da di Ung (vdi mdt thiet bl DBD tnJC tiep d mot tan sd eCia 90-700 Hz tai 3-7,8 kV). Hon nOa, cai thien eua ban do va giam ngUa cung duoc ghi nhin [8].
Trong mdt nghien cUu khdng ed nhdm chUng duoc tien hanh tren 48 benh nhan bi hpi chUng chin tieu dudng Fetykov (2009) v i cdng sU bing each sC/ dung mdt ngudn plasma nhiet do thi'p vdi mpl phan Idn cua bUc xa tia cue tim, ddi khi nhanh chong hoan thanh ehCfa benh vet thuong va giam dau trong vong 5 ngay [9].
Isbary (2010) nghien cUu tren 150 benh nhan co vet thuong nhilm triing man tinh dupe dieu tri vdi plasma argon hang ngay tU 2 den 5 phut, da ket luan dieu tri argon plasma lanh la mot ky thuat dieu tn mdi an toan, khdng dau, lam giam luong vi khuan vet thuong man tinh va thuc day qua trinh lien thUdng [10].
So vdi eac bien phap dieu tri da dUpc md ta trUdc day thi phUdng phap cua chung tdi cd mot sd uu diem nhu CO the tien hanh dieu tri ngay mac du Idp thupng bi cua Ion thuong dang bi bong trot ma khong g i y nguy ed nhilm trung nhu khi sd dung corticoid dang bdi. Day la mot phUdng phap dieu tri tai cho nen khong
gay anh hUdng toan thin.
KET LUAN
Sau khi dieu tri thanh cong 1 trudng hdp eczenij the ddng tien, vdi thdi gian dieu tn 2 tuan, benh ntian dUdc dieu tri ngoai Irii, moi lan dieu tri. vdi thdi gian 3c phut, thuong ton giam nhanh cac Uieu chi^g lim sar^
theo cae lan dieu trj. Chung toi cho rang: plasma a ^ lanh la mot hudng dieu trj cd the cho hieu qua cao (IS vdi thuong ton eczema the ddng tien va nen dUdc U^
tuc nghien cUu sau hOn ve cd che lien thudng cung nhu dUde tien h i n h nghien cUu vdi cd m i u Idn hdn.
TAI LIEU THAM KHAO
1. DaVeiga, S. P. (2012), Epidemiology of alopii dermatitis: a review, Allergy Asthma Proc. 33(3), 227-34.
2 Pham van Hien (2011), Tinh hinh cham the tangtf Vien Da lilu tU 1995-2000, Npi san Da lieu. 3.
' 3. Berth-Jones, J (2010), Eczema, Lichenificatioo Prurigo and Erythroderma, Rook's Textbook o Dermatology, Wiley-Blaekweil, 1-51.
4. Shekhter, A. B.. et al. (1998), Experimental ars clinical validation of plasmadynamic therapy of woun*
with nitric oxide. Bulletin of Expenmental Biology an Med/cme. 126(2), 829-834.
5. Lipatov, K. V,, et al. (2002), [Use of gas flowwt nitrogen oxide (NO-therapy) in combined treatment c purulent wounds], Khirurgiia. 2, 41-3. J
6. Shulutko, A. M., Antropova, N. V., and KrlugerM (2004), [NO-therapy in the treatment of purulent an necrotic lesions of lower extremities in diabetic patlente]
Khirurgiia. 12,43-6 ' 7 Daesehlein G, et dl. (2009), Selectin
antistaphylococcal activity of atmospheric pressu:
plasma jet (APPJ) on human skin, Second Intema&iK Conference on Plasma Medicine, San Antonio, Jew USA.
8. Mertens N, et al, (2009), Low Temperature Pta Treatment of Human Tissue, Second IntemaM Conference on Plasma Medicine, San Antonio, Tea
USA, I 9. Fetykov Al, et al (2009), The effectiveness off
plasma treatment of diabetic feet syndrome, compHc*
by purulonecrotic process. Second IntemM Conference on Plasma, San Antonio, Texas, USA.
10. Isbary, G., et al. (2010), A first prospedi randomized controlled trial to decrease bacterid lof using cold atmospheric argon plasma on chronic worn*
inpatients, Br J Dermatol. 163(1), 78-82.
SO LimNG VA CHAT LimNG BAO CAO CAC BIEN CO BAT LOI NGHIEM TRpNG TRONG CAC THUT NGHIEM LAM SANG TIEN HANH TAI VIET NAM TUT 2006 DEN 2013
TOM TAT
Muc tiiu: So luang va chat luang bao cao cac biin CO bit lai nghiem trong duac gOi ve Bo Y te trong cac thCf nghiim lam sang tien hanh tai Viet Nam tU nam 2006 den het nim 2013 tU dd dua ra mot so de xuat gdp phan lam tBng hiiu qua cCia cong tac bao cao bien CO bat lai nghiim trpng. Doi tupng va phuang phap nghien cUu: Nghien cuu md ta hdi cUu cac bao cao bien CO bat lai nghiem trong xay ra trong cac thCr
LE ANH TUAN, LE THI LUYEN Khoa Y Dutfc - Dai hpc Qudc gia Hi Ndi
nghiem lam sang, duac tien hanh d Viet Nam t&a 2006 din nBm 2013 va duac gUi ve Bd Y ti. Ket ij So luang bao cao gCn vi Bd Y ti la 189 trong tons 185 thi^nghiem lam sing dupe tien hinh. Trungvi\
gian gOi bao cao ta 13 ngay. Bao cao cd diydi thdng tin can thiet chiem 82.01%. Nhom thuoc W khuan dung toan than chiem t^ le bao cao SM nhat 39,68%. Ty li cac nghien cUu 'tnr. de ngH,
Y HOC THUC HANH (953) T^.
tuc triin khai la 73,54%.
TCr khoa: Biin cd bat Ipi nghiim trpng, thd nghiem lim sang.
SUMMARY
Objective: Analyse and describe reports of senous adverse events (SAEs) which were sent to Vietnam Ministry of Health in clinical tnals conducted in Vietnam from 2006 to the end 2013, with a view to suggesting some approaches to improve the quality of reporting
•SAEs. Materials and research methods: A cross- sectional study was used to analyze SAEs reporis which were submitted to Vietnam Ministry of Health from 2006 to the end 2013. Results: Of 185 clinical trials, there were 189 SAEs reporis sent to Ministry of Health. Median of submitting lime is 13 days.
Complete SEAs reports accounted for 82.01%.
-Systemic antibacterial drug group was most reported, with the largest reporting percentage 39.68%. The oroportion of studies which were suggested to be ''continuedpertorming is 73.54%.
Keywords: Serious adverse events, clinical trials.
DAT VAN DE
i Trong cac thi> nghiem lam sang (TNLS), phat hien
! 'a bao cao cae bien ed b i t Idi cd vai trd quan trpng, iham dat dUpc muc tieu khoa hpc va dao dUc trong ' ighien eUu thilf nghiem lam sing.
' O Viet Nam, viee theo doi va bao cao bien cd bi't 01 xay ra trong cae thu' nghiem l i m sang da duoc quy , ijnh trong thong tu 03/2012/tT-BYT cua Bo Y te [1 ].
Bien eo bat loi nghiem trpng (Serious Adverse ivent - SAE) la bien cd bat Ipi d bat ky lieu nao c6 the
• l i n den mot trong cac tinh hudng sau; tir vong hoac le doa tinh mang, ddi tupng tham gia nghien cUu phai '' ihap vien hoac keo dai thdi gian nam vien, gay tan tat loae mi't kha nang vTnh viln, g i y di t i t bi'm sinh, di lang thai nhi [2]. Viec giam sat chat che cac SAE se J j'am bao chat lupng nghien cUu va su an toan cho ddi - j'ong tham gia nghien cUu thU nghiem l i m sang [3], Jghien eUu n i y nham muc tieu' Md ta tinh hinh bao
cao cae SAE trong cac thU'nghiim lam sang tien hanh tai Viit Nam giai doan 2006 - 2013.
DOI TUONG VA PHUONG PHAP NGHIEN CLfU 1. Ddi tUdng nghien cufu: Cae bao cao SAE xay ra trong c i c TNLS, dUdc tien hanh d Viet Nam tU nam 2006 den nam 2013 va dupe gLfi di'n van phong Ban danh gia van de dao dUe trong nghien cUu Y sinh hoc - Bo Y te.
2. Dja diem nghien cufu: Van phdng Ban danh gia van de dao dUe trong nghien cUu Y sinh hoc - Bd Y te (BDGDD).
3. PhUdng phap nghien cUu 3.1. Thidt kd nghien ct^
Nghien CLAJ hdi ctfu dU lieu tU cae bao cao SAE gCfi ve V i n phdng Ban danh gia vi'n d l dao dUc trong Nghien cUu Y sinh hpe Bp Y te,
3.2. Cic thong sd nghien cOu Sd lupng bao cao.
Thdi gian giji bao cao.
Chat lUdng bao cao,
Thdng tin ve san pham nghien eUu.
4. Xu" ly so' lieu
Phuong phap thong ke y hoe theo chuong trinh SPSS 16.0
KET QUA NGHIEN CUu 1. So lUdng bao cao
Bang 1: Sd luong bao cao SAE va c i c TNLS lien quan
srr
1 2 3 4
Chi lieu S6 TNLS dime «6n hanh So TNLS CO bao cao SAE S6 bao cao SAE qhinhan duoc
S6 bao cao/TNLS
Kgf qua 185 27 189 Nh5 nhat = 0,Lfln nhat = 45 TQ nam 2006 den nam 2013, BDGDD da ghi nhan 189 bao cao SAE xay ra trong 27 thCf nghiem lam sang tren tong so 185 ho sd cua cac TNLS duoc tien hanh va dupc luu tai van phong BDGDD.
140 120 100 80 60 40 20
39 42
- ^ 1-9- , E-9 ^^ ,
Hinh 1: So bao cao SAE va so ttiCr nghiem lam sang qua cac nam
; Cac TNLS dang thUG hien co xu hudng tang len trong nhung nam gan day, Cac bao cao SAE nhan dirclc chu eu trong nam 2013, chiem 133/189 trong tong so bao cao (tudng duong 70,37%),
. HOC THl/C HANH (953) - SO 3/2015
2. Thdi gian g u i b a o c a o Sana 2: Thdi oian aiji tiao cao SAE
sn
1 2 3Then qian qCn bao c^o Biinq IhcB han quv iJmti Khonq dunq thd tian quy dinh
Kb6ng c6 thong bn Tonq So ngay bao cao (tnjng vi, 25*. 75'')
So bao cao 78 99 12 189
Ji\e{%]
41,27 52,38 6,35 100.00 13 (tif phan VI Ihif nhat = 5;
ti; phan vi ItiCi ba = 37,5) Trong tong sd 189 bao cao SAE ghi nhin tU nam 2006 di'n nam 2013, cd 12 bao cao khong cd thdng tin ve thdi gian giji bao cao (thieu thdng tin ve ngay bao cao, hoac thieu thong tin ve ngay xuat hien SAE, hoac ngay bao cao nam trudc ngay xuat hien SAE), Gia Iri tmng vj cilia thdi gian gCii bao cao i i 13 ngay (nho nhat
4. Thdng tin ve san pham nghien cUu
0, Idn nhat 671 ngiy) (Cac bao cao khong cd thong:
ve thai gian bao cao khdng duoc sCf dung de tinh tf gian giA bao cao tnjng binh tren)
3. Chat lUdng bao cao
Bang 3" Danh gia chat luong cua bao cao Bao cao day du cac thong tin
can (hiet Bao cao chira day du cac ttiwig
fin can Ihiet Tong
Sg luong
Jim
Chat luang bao cao duac d i n h gia theo thang Si
mm
VigiGrade [4], Bao c i o SAE cd day du cac Vh&n^i can thiet chiem ty le Idn hdn 4/5 sd bao cao nhan At (82,01%).
Tiet nidu sinh dye va hormon sinh due ^ 1,06%
He ca - xuang 1,59%
Dudng tieu hoa va chuyen hoa ^ ^ 1,59%
Thuoc chong ung t h u va tac nhan dieu hoa mien dich "" 2,12%
He ho hap Cac che pham hormon co tac dung toan than ngoai t r u
hormon sinh due
Mau va ca quan tao mau ^-^i-X-J^TT"^''!'-' ^ Hinh 2: Phan loai san pham nghien ciAi theo nhom giai phlu tac dung cua thuoc Nhom thudc chiem ti le bao cao SAE Idn nha't la
thudc khang khuan dung toan than (39,68%), tiep theo la cae thude tac dung tren he tim mach (29,63%), Cac nhom thude ehiem ti le thap nhat la thudc t i e dung len dudng tieu hoa va chuyen hoa (1,59%), he CO XUdng (1,59%) va he tiet nieu sinh due va homion sinh due (1,06%).
BAN LUAN
So lUdng bao cao SAE cd xu hudng tang ien trong nhiJng nam gan day va cao nha't vao nam 2013 vdi ty le ehiem khoang 70,37% trong tdng sd eac SAE xay ra tU nam 2006 den nam 2013 Sd bao cao tif vong trong nim 2013 chiem ty le cao 87,34% trong tdng sd 79 SAE dUdc bao cao iCr vong, Sd luang cac SAE duac bao cao tang cao trong nam 2013 cd the do hieu qua cua viee ban hanh cdng van sd 6586/BYT-K2DT [5]
eua Bp Y te ve hi^ng d i n bao cao, ghi nhan SAE trong TNLS, Sd TNLS tang ien cung cd the la nguyen
nhan d i n tdi tang sd lUdng eac SAE Ben canh do bao cao tCr vong tang cao 6 nam 2013 ed the diwci thich thong qua ban chi't ciJa ddi tUdng nghien c nhu trong nam 2013 eo 3 nghien eUu lien quani thudc sCr dung cho benh nhan HIV va c i c nghifli nay cd ty le bao e i o SAE tCr vong cao (67,09%)!
tdng sd bao cao ttrvong. i Ty le bao cao gCri dung thdi han (41,27%) vai
cao gin Khong dung thdi han (52,38%) trong ngfi nay tuang ddng vdi ket qua trong nghien euU "PI tich bao cao bien ed bi't lai nghiem trong ghiV trong eac thCf nghiem lam sang duae tien hanh ta' Nam giai doan 2011-2013" vdi ket qua tuang tJni^!
cao gCfi dung thdi han (42,3%) va bao cao giliffl
dung thdi han (50,6%) [6]. '^
Ty le bao cao day du thdng tin (8:- j i %) va ba^
chua d i y du thong tin (17,99%) tron- hien nayB ddng vdi ke! qua trong nghien cUu r, tfch ba^
Y HOC THITC HANH (9:
bien cd bat lai nghiem trong ghi nhan trong cae thur nghiem lam sing duoc tie'n hanh tai Viet Nam giai loan 2011-.2013" vdi ket qua tuOng Ung: tsao cao day ICi thong tin can thiet (83,3%) va bao cao chua day du
hdng tin (16,7%) [6].
Trong nghien cUu nay thdng tin ve san pham ighien _eUu cd xay ra SAE duac phin loai theo nhdm jiai phiu m i san pham nghien eUu tac ddng len theo )han loai ATC. Thdng tin tai Hinh 2_ T h a n loai san j h a m nghien cUu theo nhdm giai phau ma thudc tac Jung ten" nhdm thude khang khuan dung toan than ed fed luang nhieu nhi't vdi ty le 39,68%. DUng thU hai la isac thude lien quan den he tim mach cijng ehiem mot I'J le SAE kha Idn 29,63%
Nghien eUu n i y cua chung tdi cho thay trong tdng d 27 TNLS xay ra SAE. nhdm thudc khang khuan ung t o i n thin cd 12 nghien cUu chiem 75 SAE, ong khi cac thudc he tim mach cd 56 SAE trong )ng sd 3 nghien cUu Mot nghien cUu TNLS nhdm ac che pham hormon diJng toan thin ngoai trU ormon^sinh due ed 18 SAE, Ket qua eho tha'y hinh 2 idi phan anh mot phan mdi lien quan giiJa SAE va an pham nghien cUu,
KET LUAN VA KIEN NGHj
Sd luang bao cao SAE gCrt ve BDGOD trong giai jan tu nam 2006 di'n het nam 2013 la 189 bao cao Dng 185 TNLS dUOc tien h i n h v i eac bao cao nay cd I hudng tang dan theo thai gian.
Trung vj thdi gian gCfi bao cao la 13 ngay (thdi gian 10 cao nhanh nha't la 0 va cham nhal la 671 ngay).
Bao cao co day du cac thong tin can thie't chiem ty le cao 82,01% trong tdng sd 189 bao cao SAE.
TU ket qua nghien eUu tren chung tdi cd mot sd kien nghi:
Tang cudng to chUc cac Idp t i p hua'n ve ve xCr ly, bao cao SAE eho c i c nghien cUu vien. Ddng thdi, eac thdng tin trong bao c i o can duae danh gia bdi lEC/IRB cac cap.
TAI LIEU THAM KHAO
1 Bo Y te (2012). Thong tU 03/2012nT-BYT: Hudng dan ve thU thuoc trin lam sang.
2. international Conference on Harmonisation of Technical Requirements for Registration of Phannaceuticals for Human use (1996). Guideline for Good Clinical Practice E6 (Rl).
3 Internationa! Conference on Harmonisation of Technical Requirements for Registration of Ptiarmaceuticals for Human use (1995), Clinical Safety Data Management. Definitions and Standards for Expedited Reporting (ETA).
4, Bergvall T„ Noren G N , Lindquist M, (2014),
"vigiGrade' a tool to identify well-documented individual case reports and tiiqhiiqht systematic data quality issues", DrugSaA, 37(1), pp. 65-77
5, Bp Y te (2012), Hudng din bao cao, ghi nhan SAE trong thU nghiim lam sang, ban hanh kem theo Cdng van so 6586/ BYT-K2DT ngay 02/10/2012.
6, LUdng Anh Tung, Le Anh Tuan. Nguyin Hoang Anh, V6 Thi Nhi Ha, Le Ttij Luyen, Nguyin Ngo Quang, Phan tich bao cao bien co bat lai nghiem Irong ghi nhan trong cac thCt nghiem lam sang dUpc lien hanh tai Viit Nam giai doan 2011-2013, Tap chi Y hoc thuc hanh. So 12(943), nsm 2014.
NGHIEN CUfU BOdC D A U VE ALEN H U - B M 5 0 2 TREN BENH N H A N DONG KINH VA MOI LIEN QUAN VOTI PHAN ONG PHU TREN DA CUA LAMOTRIGINE TAI VIET NAM
TOM TAT
Md dau: Thud'c chdng ddng kinh la mdt trong cac lyen nhan thudng g$p gay ra phan Ung phu trin da, r phat ban dang dat san, hdi chUng qua min. hdi (ng Stevens-Johnson va hoai ti^ da nhiem doc. Vai bao cao gan diy da cho rang cd moi lien quan giOa 1 Hi-A-B'1502 vi nguy cd lam tBng phan Ung phu 1 da cOa lamotngine.
Muc tieu: Khao sat ty le alen HLA-B*1502 va moi . quan giUa alen HLA-B*1502 vdi phan Cmg phu I da cOa lamotrigine tren binh nhan ddng kinh tat
"' Nam.
Phuang phap: Nghiin cUu cit ngang trin 63 binh n ddng kinh, trong dd cd 38 doi tuang siy dung
^otrigine. Phan tich alen HLA-B'1502 bing ky thuat '^l-time PCR (Polymerase Chain Reaction) hay phan chu5i polymerase. Benh nhan sCrdung lamotngine
•g ('(nhit 3 thang mi khdng cd bat ky phan Ung phu
^•trin da duac xem la dung nap vdi thuoc.
\
TRAN QUANG TUYEN, NGUYEN hOU CONG PHAN HOANG PHUONG KHANH, CU MY HIEU HANH, VO N G U Y E N NGOC TRANG Binh vien Chuyin Khoa Ngoai Thin Kinh Qudc Te
Kit qua: Nghien cUu bao gom 63 doi tuang, trong dd cd 28 nam, 35 nU, tuoi trung binh tai thai diim chan doan la 18.4 ±12.8. T^ le cd alen HLA-B*1502 la 25,4% (16 benh nhan). Alen HLA-B'1502 gap trong 80% benh nhan cd phan Ung phu tren da do lamotrigine, nhung chi gap trong 9,1% benh nhan dung nap vdi lamotrigine Cd moi lien quan co y nghTa thong ke giOa alen HLA-B*1502 va nguy ca phan Ung phu trin da cua lamotrigine (t^ so chenh OR = 40; khoang tin cay 95%> = 3,3- 463,4, p = 0,004).
Ket luan Ket qua nghien cUu cho thay t^ le cao cHa alen HLA'B'1502 tren benh nhan dong kinh tai Viet Nam Co moi lien quan giiya alen HLA-B'1502 vdi phan Ung phu tren da cQa lamotrigine. Tnjng tuang lai can cd cac nghien cUu vdi cd miu Idn han di lam ro ket qua
Tirkhoi: Benh nhan ddng kinh, phan Ung phu tren
,OC THUC HANH (953) - S6 3/2015
