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Nghien cuuduoc SThong tin thudc

I JOURNAL OF PHARMACEUTICAL RESEARCH AND DRUG INFORMATION

Nghien cull dirge & Thong tin thuoc 2017, Tap 8, So 1 Journal of pharmaceutical Research and Drug information 2017, Vol 8, N°1

M U C L U C So 1,2017

BAI NGHIEN CUU

2 Tong quan he thong va phan tkh gpp cac nghien ciiu quan sat ve bien co bat Idi cua thuoc trong dieu tri lao da khang/lao sieu khang

Nguyen Thi Thuy', Nguyen Hong Duong1, Cao Thi Thu Huyen', Vu flinh Hoa', Nguyen Hoang Anh !, Nguyen Viet Nhung'

'Berth mn Phoi Bang Hang, 'fritting Bgi hoc Bddc hit Mi

C O N T E N T S No 1,2017

RESEARCH

Adverse drug events in the treatment of multidrug and extensively drug - resistant tuberculosis: a systematic review and meta-analysis

Nguyen Thi Thuy, Nguyen Hong Duong, (ao Thi Thu Huyen, Vu Dinh Hoa, Nguyen Hoang Anh, Nguyen Viet Nhung

'national Lung Hospital, 'Ha Hoi University of Pharmacy

1 0 Loai bd anh hiking nen trong phan tich khang sinh cloramphenicol bang cot sac kyai life mien dich

Nguyen Brie Thinh ' ; , Chu Pham Nggc Son', Tran l inh Thucic' 'Wen Pre'Cong rang DM phSHo ChiMinh,

'JnHxg Bgi hoc khoa hoc Idnhien (BHBC-HCM), 'Leung tarn Sac ky Hai Sang

Removal of sample matrix effects for chloramphenicol analysis by affinity immunochromatography column

Nguyen DucThinh, Chu Pham Ngoc Son, Tran Linh Thuoc 1 Institute of Public Health

'University ofSciencesfVietnam national University Ho Chi Minh City] 'Lighthouse Chromatography Center

1 5 Xay dung quy trinh dinh lUdng ddng thiri paracetamol, ibuprofen va tap Simultaneous determination of paracetamol, ibuprofen and related C cua ibuprofen bang phddng phap UPLC/DAD impurity of ibuprofen by UPLC/DAD

Nguyen Thi Nggc Van, Tran Thi Tie't Nghia Nguyen Thi Ngoc Van, Tran Thi Tiet Nghia Khoa Ddpcjnlimg Dai hoc YDircc Can Ihd faculty of Pharmacy-Can Iho University of Medicine and Pharmacy

21 Tong hgpva thOrtac dung Uc die enzym glutaminyl cyclase cua mot so dan chat pyrimidin cua N-(5-methyl-1 H-imidazol-1 -yl) propyl-N' - (3-methoxy-4-alkyloxyphenyl) thiourea

Tran Phirong Thao1, Tran Thi Thu Hien!

'InldngDgihgcDiigcHdHpi, 'Hgcvien YBagchgcCdtruyen Vietnam

Synthesis and evaluation of human glutaminylcyclase inhibition activity of new pyrimidine derivatives bearing N-(S-methyl-1 H-imidazol-1 -yl) propyl-N'-(3-methoxy-4-alkyloxyphenyl) thiourea

Tran Phuong Thao, Tran Thi Thu Hien 'Hanoi University of Pharmacy, 'institute of Iraditional Medicine and Pharmacy Vietnam

2 6 Nghien cUu dac diem hinh thai va xac dinh lai ten khoa hoc cua cay thuoc Tdmanh

Nghiem Dure Trgng, Tran Van On', Nguyen Van HieV Tracing Bgi hoc Dupe Ha Hgf

'Vien Thdc vgthgc, Wen ban lam khoa hoc Trung Owe

Study on morphological characteristics and identify scientific name of the medicinal plant named "To manh"

Nghiem Due Trong1, Tran Van On', Nguyen Van Hieu' 'Manor University of Pharmacy

'Institute of Botany, Chinese kademy of Sciences, Beijing 100093, China

3 0 ^ c dung giam ho, long derm cua cao dac hai thudc AZKtren md hinh thuc nghiem

Nguyen Manh Tuyen, Phung Hoa Binh, Do Thi Thu Thiiy, Nguyen Thuy Duong InriSngBgihgcDtlgcHaHoi

Antitussive and expectorant effects of the soft extracts made from AZK remedy on experiment models

Nguyen Manh Tuyen, Phung Hoa Binh, Do Thi Thu Thuy, Nguyen Thuy Duong Hanoi University of Pharmacy

THONG TIN THUOC • CANH GIAC DUOC

34 C a c bien chitog tim mach cua nhiem toan ceton

DIEM TIN HOAT DONG

Nguon: 05 Ptorm. 2016; 41(21:39-42 Nguoi djch: LeThj Quynh Giang, Luong Anh Tung

3 8 H ? c tap, quan triet Nghi quyet Hoi nghj Ian thii W Ban Chap hanh Trung Udng Oang (khda XII) va "NhuTng ndi dung cdban cua tutudng, dao due, phong each HdChiMinh"

3 9 Cong bd va trao Quyet dinh bd nhiem, bd nhiem lai vien chifc quan ly cac ddn vi

Nghien cull dutfc & Thong tin thuoc 2017, Tap 8, So 1, trang 2-9

BAI NGHIEN ClTU •

Tong quan he thong vd phdn tich gop cdc nghien cuu quan sat ve bien cb bat lai cua thubc trong ctieu tri lao da khang/lao sieu khang

Nguyen ThjThuy1 , Nguyen Hong Duong 2 , Cao Thi Thu Huyen2 , Vu Dinh Hoa2 , Nguyen Hoang Anh 2 , Nguyen Viet Nhung 1

'Benh vien Phoi Trung dang, 2Trudng Dai hoc Dugc Ha Ngi

S U M M A R Y

Adverse drug events (ADE) have been mentioned as the most crucial obstacle in the management of multi/extensively drug-resistant tuberculosis (MDR/XDR-TB) using second-line drug chemotherapy. The information of such ADE was found diverse among studies and a systematic summary was therefore required to assist clinical practice. The study aimed to identify the proportion and type of ADEs reported in published medical literature. A systematic search for ADEs in MDR/XDR-TB treatment from Medline in January 2016 was carried out and subsequently the search result was reviewed under pre-defined criteria. Extracted data was summarized and the pooled incidence for each specific ADE and for cases with at least one ADE was presented. Of 1504 searched articles, 69 were selected for the review. A total of 5313 (68.2%) patients in 49 studies experienced at least one ADE. In addition, 2000 patients (21.8%) in 46 studies required change of MDR/XDR-TB treatment. The most three common side effects were gastrointestinal disorders (39.6%), red blood cell disorders (18.8%/), and general disorders (18.3%). Most of the I2 values were over 90%. These results revealed that ADE was found to be common in MDR/XDR-TB treatment. The high heterogeneity of the result suggested a wide variation among studies in assessing and reporting ADE during the treatment of MDR/XDR-TB.

TCfkhda: Bien co bat Igi, MDR-TB, XDR-TB, tong quan he thong, phan tfch gqp.

Oat van de Lao khang thuoc da va dang t rd thanh mot t h d

thach Idn doi vdi viec kiem soat benh lao tren toan cau. Rieng t rong nam 2014, da co khoang 190 000 t rddng hop t d vong do lao da khang (MDR-TB). Lfdc t inh chl co 50% so benh nhan MDR-TB dugc dieu trj khdi va da co khoang 9,7% so ca MDR-TB bi sieu khang thuoc (XDR-TB). Viet Nam nam t rong nhdrn 27 quoc gia co ganh nang lao da khang cao nhat the gid i , xep t h d 11/20 nUdc co so lupng benh nhan MDR-TB nhieu nhat [5]. Benh nhan MDR/XDR-TB phai s d d u n g nhieu thuoc dong thdi vdi thd i gian dieu trj benh keo dai, dac biet cac thuoc lao hang hai thudng co doc t inh cao hon thuoc lao hang mot , dan den tang kha nang xuat hien bien co bat Igi. Vi vay, viec nhan d ien, danh gia va xd t r i bien co bat Igi t rong dieu tr i lao da khang dong mot vai t ro quan t rgng

t rong viec sd dung thuoc hgp ly, an toan va dieu trj thanh cong MDR/XDR-TB [9].Tuy nhien, t hong t in ve cac bien co do thuoc dieu trj MDR/XDR-TB thu ddgc tren thdc te t d he thong bao cao t u nguyen tai Viet Nam con rat han che do so Idgng va chat lugng bao cao chda cao. Ben canh do, cac nghien cdu theo doi chu dgng bien co bat Igi cua thuoc dieu trj lao mdi bat dau ddgc tr ien khai t rong nhdng nam gan day tai mot so co sd t rgng d iem va chua cong bo ket qua dau ra. Tren the g id i , da cd nhieu ngh ien cdu ghi nhan va phan t ich ve bien co bat Igi t rong dieu trj MDR va XDR-TB, nhdng ket qua cua cac nghien cdu rieng le kho phan anh dugc day du ve bien co bat Igi va nhdng yeu to anh hudng den sd xuat hien cua bien co khi sd dung nhdng phac do dieu trj MDR va XDR-TB. Mac du mot nghien cdu tong quan he thong va phan tich ggp ve bien co bat Igi t rong dieu trj lao

2

Nghien cull dutfc & Thong tin thuoc 2017, Tap 8, So 1, trang 2-9 ^

B A l NGHIEN c G f u *

da khang da dugc t ien hanh vao nam 2012 [10], nhung ke t d thdi d iem do den nay da cd them nhieu nghien cdu dugc thUc hien bo sung them vao dd lieu bien co bat Igi khi dieu tri MDR/XDR-TB. Do vay, de cd ddgc gdc nhin tdong ddi toan dien ve bien co bat Igi cua thuoc t rong dieu tr i lao da khang va sieu khang da dugc ghi nhan tren the gidi, t d d d cung cap nhdng thong t in hdu ich phuc vu cho cdng tac dieu tri MDR/XDR-TB, nghien cdu nay ddgc thdc hien vdi muc t ieu phan tich tan suat xuat hien cac bien co bat Igi xay ra t rong dieu trj lao da khang/sieu khang thudc thong qua tdng quan he thong va phan t ich ggp t d cac nghien cdu quan sat.

Doi tvong va phvong phdp nghien cuu Doi twang nghien cdu Cac bai bao t d nguon d d lieu PubMed/Medl ine

dugc cap nhat den thang 1/2016. Chien luge t im kiem la sd dung MeSH de thu dugc danh muc cac t d dong nghia cua "MDR-TB","XDR-TB" va "Adverse Drug Events"; gidi han ngdn ngd la t ieng Anh.

Phi/Ong phdp nghien cdu Quy thnh Ida chgn nghien cdu Hai thanh vien t rong nhdm nghien cdu dgc t ieu

de va torn tat cua cac nghien cdu mot each dgc lap va soat cheo. Neu cd ket qua khac nhau, t ien hanh thao luan lai hoac xin y kien thanh vien t h d ba t rong nhdm nghien cdu de thong nha't. Sau do, dgc ban day du cac nghien cdu da chgn. Nhdng nghien cdu thda man tieu chuan Ida chgn va khdng nam trong tieu chuan loai t rd ddgc dda vao t rong tong quan he thong.

Tieu chudn Ida chon Cac nghien cdu quan sat phai thda man nhdng

t ieu chuan nhd sau: cd d d lieu dau ra la bien co cd hai cua thudc; nghien cdu ve lao da khang va lao sieu khang thuoc; la tai lieu cap mot; phac do dieu trj lao cua cac nghien cdu cd bao gdm cac thuoc hang hai; ngdn ngd bang Tieng Anh.

Tieu chudn logitrd Cac nghien cdu ddgc loai bd neu doi t dgng

nghien cdu cd tre em, phu nded thai, ngddi caotuo i . Ngoai ra, cac nghien cdu bao cao ca, bao cao chuoi, nghien cdu benh chdng, nghien cdu chi quan sat mot bien cd bat Igi hoac chi quan sat bien cd bat Igi cua mot thudc cung khdng ddgc dda vao tong quan he thong .

Ddnh gid chat Idgng nghien cdu Sddung thang NOS (Newcastle-Ottawa Scale) [6]

de danh gia chat lugng cac nghien cdu trudc khi dda vao phan tich ggp dda tren 3 t ieu chi: Kha nang Ida chgn (tdi da 4 d iem); kha nang so sanh (tdi da 2 diem); ket qua dau ra (toi da 3 diem).Thang diem nay

da dugc nhieu nghien cdu sd dung de danh gia chat lugng t rong phan t ich ggp, dac biet la t rong cac phan tich danh gia bien co bat Igi cua thuoc dieu trj lao [2], [3], [4]. Trong tong quan he thong nay, nhdm nghien cdu quy d jnh nhdng nghien cdu co mdc d iem danh gia theo thang NOS dat t d 5 d iem t rd len (> 50%) ddgc coi la nghien cdu dat chat Idgng de dda vao t ien hanh phan tich ggp.

Chietxudtddlieu

Mot thanh vien t rong n h o m nghien cdu t ien hanh phan loai va nhap d d lieu theo cac trUdng d d lieu xac djnh, thanh vien t h d hai t rong nhom nghien cdu kiem tra lai. Trong tracing hgp co y kien khdng dong nhat, t ien hanh thao luan lai hoac xin y kien thanh vien t h d ba t rong n h o m nghien cdu. Cac trUdng d d lieu lien quan den nghien cdu dagc chiet xuat bao g o m : Thong t in chung ve nghien cdu (ten tac gia chinh, nam xuat ban, thiet ke nghien cdu, dja diem nghien cdu, thd i gian t ien hanh nghien cdu, cd mau); dac diem benh nhan (tuoi t rung binh, gidi t inh, t ien sdd ieu trj lao, dong nhiem HIV, sd thuoc dieu trj lao bj khang t rung binh); phac do dieu trj (thdi gian dieu trj, so thuoc t rung binh t rong phac do, phac do chuan hda/ca nhan hda); ket cudc cua ADE lien quan den dieu trj (sd benh nhan xuat hien it nhat 1 ADE, so benh nhan xuat hien it nha't 1 ADE nghiem t rpng, sd benh nhan t d vong do ADE, sd benh nhan phai thay ddi phac do do ADE, so benh nhan xuat hien tdng loai ADE).

Phdn tich ddlieu Ket qua tdng quan he thong ddgc t r inh bay dddi

dang bang torn tat t hong t in cua cac nghien cdu dat tieu chuan. Sddung phan mem Microsoft Excel 2010. Sd dung md hinh anh hadng ngau nhien de phan tich va ddc Idgng ket qua gdp bang phan mem Open MetaAnalyst [1], [7]. Do dj biet gida cac nghien cdu dugc danh gia thong qua chi so I2. Tien hanh phan t ich gdp tdng n h d m nhd /phan t ich dudi nhom (sub-group) theo mot so tieu chive dac diem quan the benh nhan, cd mau nghien cdu, tien sddieu tr j , . . .

Ket qua nghien cuu Td 1504 bai bao ddgc t im thay, qua cac bade Ida

chgn va loai t rd , da co 69 nghien cdu ddgc dda vao tdng quan he thong . Quy t r inh lua chgn cac nghien cdu s d d u n g t rong tdng quan he thong va phan tich gdp dugc t r inh bay d hinh 1. (Xem bang)

Ddc diem ede nghien cdu ddgc Ida chgn Ngi dung thu nhap t d 69 bai bao dugc t r inh bay

torn tat t rong bang 1. Trong sd 69 nghien cdu quan sat ddgc Ida chgn, cd 39 nghien cdu hoi cdu va 30 nghien cdu tien cdu. Cac nghien cdu ddgc thgc hien

3

Nghien culidifoc & Thong tin thuoc 2017, Tap8, S61,trang 2-9

BAI NGHIEN CQU •

tai 35 quoc gia, t rong do An Dp la nude co nhieu nghien cdu nhat vdi 15 nghien cdu. Dac biet, co 1 nghien cdu dupe thUc hien tai Viet Nam. CP mau cua nghien cdu dao dpng tCr 9 den 1390 benh nhan, co 37 nghien cdu co cd mau dudi 100 va 32 nghien cdu coed mau tren 100 benh nhan. Quan the nghien cdu cd tuo i t rung b inh t d 26 den 46 tuo i , t rong do cd 49 nghien cdu co tuo i t rung b inh nam t rong khoang t d 30 den 40 tuo i . Phan Idn benh nhan am t inh vdi HIV va da cd t ien sd dieu tr i lao. Ve mat phac do dieu trj, cd 41 nghien cdu sd dung phac do ca nhan hda, 26 nghien cdu sd dung phac do chuan, 1 nghien cdu bao gom ca phac do ca nhan hda va phac do chuan, 1 nghien cdu khdng rd thong t in ve phac do sddung .

Bang 1. Mot so thong tin cua cac nghien cdu dugc dUa vao tong quan he thong

STT Ta/ - n i a n a n t i o n /"i ia l a c y la UdU l ie l l l U d

nghien aifu

N a m n a m

xuat ban Co mau (n)

T i o n c iV r t i bn t r i 1 Ic l l >U U lcU I I I

TB (%)

T u l b rtnnn n h i o m i v i c u u n y m u c i n

HIV(%)

r i l a c u u

dieu t r j

Sn RN n a n i t J U DIM i ja p i i

nhat 1 ADE

1 Ng.B.Hoa 2015 282 Chuan 143

2 Pym 2015 233 94,8 4,0 Chuan 219

3 Meressa 2015 612 98,5 21,7 Chuan 544

4 Cavanaugh 2016 77 100 0(n=15) Khong rd 55

5 Lytvynenko 2014 484 86 3,1 Ca nhan hda 226

6 Vaghela 2015 101 100 2,0 Ca nhan hoa

7 Kuaban 2015 150 20,0 Chuan

8 Kibleur 2015 231 59 Ca nhan hda

9 Avong 2015 460 10,0 Chuan 203

10 Hire 2014 110 0,0 Chuan 55

11 Piubello 2014 65 98 1,7(n=58) Chuan 41

12 Charles 2014 110 88,88 25,0 Ca nhan hda 61

13 Jain 2014 130 Chuan

14 Bharty 2014 930 Chuan

15 Mpagama 2013 61 98 14,0 Chuan 49

16 Shean 2013 115 42,0 Ca nhan hda 67

17 Jiang 2013 158 74 0,0 Ca nhan hda 81

18 Walt 2013 1390 91 39,1 Chuan

19 Rodriguez 2013 289 92,4 4,5 Chuan va ca

nhan hda 287

20 Brust 2013 91 84,0 Chuan 90

21 Sagwa 2012 59 92 53,0 Ca nhan hda 53

22 Isaakidis 2012 67 92,5 100,0 Ca nhan hda

23 Bhatt 2012 81 53.1 1,2 Chuan 76

24 Brust 2012 80 82,5 Chuan 70 (n=71)

25 Xu 2012 18 100 0,0 Ca nhan hda 17

Tong so nghien cuu tim dupe tren Pubmed (N=1504)

Doc tieu de va torn tat (N=l 504)

Tim doc ban d4y du (N=288)

Cac nghien cuu dat tieu chuan (N=101)

Nghien cuu dupe dua vao tong quan he thong va ph^n tich gpp (N=69)

1 -Khongphiihop vui tieu chuan lua chpn va I tieu chuan loai tructia tong quan (N—1216) |

I J

I -Khong co toan van bang tieng Anh N—l * ^| -Khong tim dupe ban day diiN—8 I I - Khong phu hop voi tieu chuan lua chgn I

va tieu chuan loai truciia tong quan j 1 (N-178)

_ _>| -Chi quan sat mot loai ADE ; hoac chi . quan sat ADE ciia mot thuoc (N=32) I

Hinh 7 . Quy trinh Itfa chgn cac nghien cifu

4

Nghien cull difcfc & Thong tin thudc 2017, Tap 8, So 1, trang 2-9

BAI NGHIEN CL/U

STT Tac gia dau t ien cua

nghien ciifu Nam

xuat ban Cor mau (n)

Tien surdieu t r i TB (%)

Ty le dong nh iem HIV(%)

Phacdo

d ieu t r i

So BN gap i t

nha t 1 ADE

26 Carrol 2012 655 66 Ca nhan hoa

27 Miller 2012 407 Ca nhan hda 367

28 Isaakidis 2011 58 91 (n=56) 100,0 Ca nhan hda 26

29 Abbate 2012 17 94/1 0,0 Ca nhan hda 9

30 Kennedy 2011 1? 84,6 14,0 Chuan 12

31 Singla 2012 29 100 0,0 Ca nhan hda

32 Lee 2011 171 49,4 0,6 Ca nhan hda 81

33 Joseph 2011 38 100 0,0 Chuan 33

34 Kvasnovsky 2011 206 100 55,4 Ca nhan hda

35 Dheda 2010 174 72 47,0 Ca nhan hda 67(n=115)

36 Van Deun 2010 427 100 Chuan 203

37 Anger 2010 16 100 19,0 Ca nhan hda 16

38 Bloss 2010 1027 63 3,1 Ca nhan hda 807

39 Singh Datta 2010 52 1,9 Chuan 36

40 Malla 2009 175 98,2 (n=166) Chuan

41 Karagoz 2009 142 100 0,0 Ca nhan hda 79

42 Baghaei 2011 80 5,0 Chuan 45

43 Pawar 2009 25 65 8,0 Ca nhan hda

44 Singla 2009 126 100 0,0 Chuan 73

45 O'Donnel 2009 60 70 72,0 Ca nhan hda 31

46 Jacob 2009 23 56,5 5(n=21) Ca nhan hda 23

47 Keshavjee 2008 608 99,5 0,8 Ca nhan hda 407

48 Prasad 2005 46 100 0,0 Chuan 16

49 Masjedi 2008 43 100 0,0 Chuan

50 Shin 2007 244 100 Ca nhan hda 179 51 Cox 2007 87 100 Ca nhan hda

52 Thomas 2007 66 100 Ca nhan hda 39

53 Uffredi 2007 45 47 20,0 Ca nhan hda 15

54 Escudero 2006 25 88 0,0 Ca nhan hda 7

55 Codecassa 2006 38 54 5,3 Ca nhan hda 32

56 Torun 2005 263 0,0 Ca nhan hda 182

57 Nathanson 2004 818 Ca nhan hda

58 Palmero 2004 141 64,5 0,0 Ca nhan hda

59 Van Deun 2004 58 Chuan

60 Yew 2003 99 0,0 Ca nhan hda 41

61 Furrin 2001 60 100 1,7 Ca nhan hda 60

62 Tahaoglu 2001 158 100 Ca nhan hda

63 Singla 2001 9 100 0,0 Chuan 7

64 Geerligs 2000 44 34 0,0 Ca nhan hda 44

65 Wai Yew 2000 63 65,1 100,0 Ca nhan hda 25

66 Mannheimer 1997 13 23 100,0 Ca nhan hda 4

67 Lee 1996 36 100 Ca nhan hda 10

68 Hadiarto 1996 57 100 0,0 Chuan

69 Telzak 1995 25 32 0,0 Ca nhan hda

Nghien cull difcfc & Thong tin thudc 2017, Tap8, So 1,trang 2-9

BAl NGHIEN cCfu

Phan tich gdp ve bien cdbdt Igi trong dieu tri lao da khang va lao sieu khdng thudc

Ket qua danh gid chat It/gng cac nghien cCfu V6i 69 bai bao dupe dda vao tong quan he thong,

chung to i thUc hien cham d iem de danh gia sit dong deu ve chat lupng cua cac nghien cud trudc khi dua vao t ien hanh phan tich gpp. Ket qua: tat ca nghien cud deu dat m u t >5 diem (tren thang toi da 9 diem) t rong tat ca cac t ieu chi danh gia nen deu dupe dua vao phan t ich gpp, cu the: 23 nghien cud (33%) dat 8 d iem, 40 nghien cud (58%) dat 7 diem va 6 nghien cud (9%) dat 6 d iem.

Phan tich gdp ve ty le xuat hien bien co chung

Bang 2. Phan tich ggp ve ty le xuat hien bien co

S t u d i e s E s t i m a t e ( 9 5 1 C . I . ) E v / T r t

N g u y e n B i n h H o a 2 0 1 5 : 5 0 7 ( 0 4 4 9 , - 5 6 5 ) 1 4 3 / 2 8 2

A l e x a n d e r S . P y m 2 0 1 5 0 -; ( 0 9 0 1 , 7 9 6 4 ) 2 1 9 / 2 3 3

M e r e s s a 2 0 1 5 0 B 5 7 I 0 8 6 1 , 9 1 1 ) 5 4 4 / 6 1 2

C a v a n a u g h 2 0 1 6 0 7 1 4 1 6 0 4 , 8 0 4 ) 5 5 / 7 7

L y t v y n e n k o 2 0 1 4 0 1 4 2 3 , 5 1 2 ) 2 2 6 / 4 8 4

A v o n g 2 0 1 5 ) ( 4 1 ( 0 3 9 7 , 7 4 8 7 ) 2 0 3 / 4 6 0

H i r e 2 0 1 4 3 5 0 0 1: 4 0 8 , 5 9 2 ) 5 5 / 1 1 0

P i u b e l i o 2 0 1 4 6 3 1 ( 0 5 0 8 , : 7 3 9 ) 4 1 / 6 5

C h a r l e s 2 0 1 4 0 5 5 5 4 6 1 , ; 6 4 5 ) 6 1 / 1 1 0

M p a g a m a 2 0 1 3 0 E 0 3 i 6 8 5 , 8 8 5 ) 4 9 / 6 1

K a r e n S h e a n 2 0 1 3 0 5 8 3 i : 4 9 1 , 6 6 9 ) 6 7 / 1 1 5

J i a n g 2 0 1 3 0 5 1 3 1 4 3 5 , 5 9 0 ) 8 1 / 1 5 8

R o d r i g u e z 2 0 1 3 : 7 7 3 ( 0 9 7 3 , 9 9 8 ) 2 8 7 / 2 8 9

B r u s t ( 1 ) 2 0 1 2 0 78 7 10 9 2 6 , 9 9 8 ) 9 0 / 9 1

S a g w a 2 0 1 2 0 8 =6 10 7 9 2 , 7 9 5 4 ) 5 3 / 5 9

B h a t t 2 0 1 2 0 9 3 8 (0 8 6 0 , 9 7 4 ) 7 6 / 8 1

B r u s t ( 2 ) 2 0 1 3 0 8 7 5 ( 0 7 8 3 , 0 9 3 1 ) 7 0 / 8 0

X u 2 0 1 2 0 9 4 4 10 6 9 3 , 9 9 2 ) 1 7 / 1 8

M i l l e r 2 0 1 2 0 9 0 8 (0 8 6 9 , 0 9 2 7 ) 3 6 7 / 4 0 7

I s a a k i d i s 2 0 1 1 0 141 I? 1 3 2 6 , 0 5 7 7 ) 2 6 / 5 8

A b b a t e 2 0 1 2 0 5 2 9 1 3 3 0 3 , 7 4 5 ) 9 / 1 7

K e n n e d y 2 0 1 1 0 9 2 3 10 6 0 9 , 9 8 9 ) 1 2 / 1 3

L e e ( 1 ) 2 0 1 1 0 4 7 4 1 3 4 0 0 , 5 4 9 ) 8 1 / 1 7 1

J o s e p h 2 0 1 1 0 • ( 0 7 2 0 , 9 4 4 ) 3 3 / 3 8

D h e d a 2 0 1 0 0 3 8 5 ( 7 3 1 6 , 0 4 5 9 ) 6 7 / 1 7 4

V a n D e u n 2 0 1 0 0 4 7 5 ( 0 4 2 8 , 5 2 3 ) 2 0 3 / 4 2 7

A n g e r 2 0 1 0 0 - 7 - : 10 6 6 4 , 9 9 8 ) 1 6 / 1 6

B l o s s 2 0 1 0 0 ( 0 7 6 0 , 8 1 0 ) 8 0 7 / 1 0 2 7

S i n g h D a t t a 2 0 1 0 0 i -i ( 0 5 5 5 , 8 0 2 ) 3 6 / 5 2

K a r a g o z 2 0 0 9 0 - 5 8 [ 0 4 7 4 , 6 3 6 ) 7 9 / 1 4 2

B a g h a e i 2 0 1 1 0 i 1 1 ( 0 4 5 3 , 6 6 7 ) 4 5 / 8 0

S i n g l a ( 1 ) 2 0 0 9 0 5 7 9 ( 0 4 9 2 , 6 6 2 ) 7 3 / 1 2 6

O ' D o n n e l 2 0 0 9 0 5 1 7 ( 0 3 9 2 , 6 3 9 ) 3 1 / 6 0

J a c o b 2 0 0 9 0 7 7 ? ( 0 7 4 1 , 9 9 9 ) 2 3 / 2 3

K e s h a v j e e 2 0 0 8 0 5 6 7 <o 6 3 1 , 0 7 0 6 ) 4 0 7 / 6 0 8

P r a s a d 2 0 0 5 0 3 4 : ( 0 2 2 5 , 4 9 5 ) 1 6 / 4 6

S h i n 2 0 0 7 0 7 34 (0 6 7 5 , 0 7 8 5 ) 1 7 9 / 2 4 4

T h o m a s 2 0 0 7 0 ( 0 4 6 9 , 0 7 0 2 ) 3 9 / 6 6

U f f r e d i 2 0 0 7 0 3 3 3 ( 0 2 1 2 , 0 4 8 2 ) 1 5 / 4 5

E s c u d e r o 2 0 0 6 0 3 8 0 ( 0 1 4 0 , ' 4 B 2 ) 7 / 2 5

C o d e c a s s a 2 0 0 6 0 8 4 2 ( 0 6 9 0 , 0 9 2 7 ) 3 2 / 3 8

T o r u n 2 0 0 5 0 6 9 2 ( 0 6 3 4 , 3 7 4 5 ) 1 8 2 / 2 6 3

Y e w 2 0 0 3 0 4 1 4 ( 0 3 2 2 , 0 5 1 3 ) 4 1 / 9 9

F u r r i n 2 0 0 1 0 7 7 8 ( 0 8 8 2 , 7 9 9 9 ) 6 0 / 6 0

S i n g l a ( 2 ) 2 0 0 1 0 7 7 8 ( 0 4 2 1 , 0 9 4 4 ) 7 / 7

G e e r t i g s 2 0 0 0 0 7 8 7 ( 0 8 4 6 , 0 9 9 9 ) 4 4 / 4 4

W a i Y e w 2 0 0 0 0 3 77 ( 0 2 8 4 , 1 5 2 1 ) 2 5 / 6 3

M a n n h e i m e r 1 9 9 7 0 3 0 S ( 0 1 2 0 , 0 5 9 1 ) 4 / 1 3

L e e ( 2 ) 1 9 9 6 0 2 7 8 ( 0 1 5 6 , 0 4 4 4 ) 1 0 / 3 6

O v e r a l l ( l « 2 « 9 5 . 0 7 % , P < 0 . 0 0 1 ) 0 6 8 2 ( 0 6 2 4 , 0 7 3 5 ) 5 3 1 3 / 7 8 7 5

*7tfc gia cohort 1 bai bao Suae ky hieu (1), (2,

Sd NC

99P

So BN xuat hien

ADE

So BN don

Ty le xuat hien ADE

(95% CI) (%)

Chi so

BN xuat hien it nhat 1 ADE

49 5313 7875 68,2 (62,4-73,5) 95,07

BN xuat hien it nhat 1 ADE nghiem trong

21 571 2526 26,9 (20,0-35,2) 91,77

BN thay doi phac do do ADE

46 2000 4959 21,8 (17,0-27,4) 95,67

BNtufvong do ADE 11 112 2709 3,2 (0,2-5,2) 61,77

ben cgnh nam xuat ban

Hinh 2. Bieu do ggp ve ty le xuat hien it nhat mot ADE

0 56 L o g r t P r o p o r t i o n

6

Nghien cuu duoc & Thong tin thuoc 2017, Tap 8, So 1, trang 2-9

BAI NGHIEN CQU

Phan tich gdp ve so ty le xuat hien it nhat mot bien cd bat Igi

Co 49 nghien cud thu thap thong t in ve so lut ing benh nhan xuat hien it nhat mot ADE. Trong do, cd mau gpp la 7875 benh nhan va so benh nhan xuat hien it nha't 1 ADE la 5313 benh nhan. Ty le gpp thu duoc la 68,2% (95% CI: 62,4% - 73,5%).

Phan tich gdp ve bien cd bat Igi tren tdng he co quan

Bang 3. Ty le xuat hien ADE tren cac he co quan

STT Bien cd bat Igi Sd NC

Cn RM > 0 DIM

xuat hien ADE

Tong so BN

phfli nhiem

Ty le xuat hien ADE

IQCOX. cn itt/A

Chi so l 2

(%)

1 Roi loan tieu hoa 47 3415 7910 39,6 (30,4- 49,6) 97,79

2 Rdi loan hong cau 6 61 856 18,8 (04,4-53,9) 92,67

3 Rdi loan toan than

10 278 2088 10 -}

' (12,7-25,7) 89,43

4 Roi loan than kinh trung uong va than kinhngoaivi

50 1715 9676 15,2 (12,0-19,2) 94,91

5 Roi loan ca xiiong khcfp

41 1783 8975 14,7 (10,9- 19,5) 96,80

6 Rdi loan thinh giac va tien dinh

45 1517 8967 14,0 (10,8-18,0) 95,13

7 Rdi loan tarn than 40 1511 8612 13,6 (10,3-178) 95,73

8 Rdi loan chuyen hda

17 985 5984 1 1 , 6 (7,0-18,4) 97,66

9 Rdi loan da va td* chdc dudi cua da

43 725 8741 8,8 (6,7-11,4) 91,08

10 Rdi loan tai cho 8 125 1804 6,5 (1,7-21,4) 96,86

11 Rdi loan not tiet (suygiap)

20 418 6030 64

' (3,8-10,4) 95,27

12 Roi loan bach cau 8 44 1537 6,0 (1,5-21,1) 93,58

13 Rdi loan gan mat 37 569 8604 5,0 (3,6-7,0) 91,49

14 Rdi loan tiet nieu 23 249 5490 4,3 (3,0-6,2) 85,53

15 Rdiloan thjgiac 19 134 4650 3,3 (2,3-4,6) 66,15

Nhufng bien co tren he t ieu hoa, roi loan hong cau, roi loan toan than, roi loan t ren he than kinh t rung uong va tai cho, roi loan he CO xuOng khdp la nhdng bien co co ty le gpp cao nhat. Bien co bat Ipi tren dudng t ieu hoa co ty le gpp cao rd ret: 34,8% (95% CI: 26,2% - 44,6%). Cac roi loan t ren he than kinh t rung uOng, he t ieu hoa, roi loan th inh giac va tien d inh dupe nhieu nghien cud ghi nhan nha't.

Kit qua phan tich ggp difcri nhom

Bang 4. Phan tich gdp dudi nhom ve ty le xuat hien it nhat 7 ADE

Tieu chi So NC Ty le xuat hien it nhat 1

ADE(95%CI)(%) Chi so I 2

(%)

Quan the nghien ciu

Chau A 24 61,2 (54,3-67,6) 92,76

Cac khuvilc khac 24 74,9 (65,4-82,5) 96,01

CaChauAvacacKVkhac 1

Thiet ke nghien aitu

Tien cdu 16 62,8 (51,3-72,9) 92,73

Hoi cdu 33 70,9 (64,0-77,0) 95,68

Tien si dieu triftheo % so benh nhan tham gia nghien chu da ting dieu hi lao)

<75% 12 63,8 (48,9-76,5) 94,70

> 75% 26 71,2 (63,0-78,1) 95,54

Khdng cd thong tin 11 67,4 (55,2-77,7) 95,84

Bong nhiem HIV

Khdng nhiem HIV 14 59,1 (50,4-67,2) 83,69

Co dong nhiem HIV 29 73,5 (65,7-80.0) 95,93

Khdng cd thong tin 6 61,1 (42,5-77,0) 97,32

Thhi gian dieu trj

<18 thang 18 63,7 (53,4-72,9) 91,95

>18thang 27 72,1 (65,1-78,1) 95,42

Khdng cd thong tin 4 53,8 (18,9-85,3) 97,45

Cimiu

<100 29 70,7 (61,5-78,4) 88,01

>100 20 66,9 (58,4-74,3) 97,42

Trong tong so 49 nghien cud co ghi nhan ty le xuat hien it nhat 1 ADE, phan t ich dodi nhom da dupe thud hien va ket qua dupe torn tat t rong bang 4. Trong so 24 nghien cUu tai chau A, ty le gpp xuat hien it nha't 1 ADE la 61,2% (95% CI: 54,3 - 67,6), con vdi 24 nghien cdu t ien hanh tai cac khu vUc khac, ty le gpp cd xu hudng cao hon (74,9%, 95% CI: 65,4% -82,5%). Tuong tU, ty le gap ADE gpp tU cac nghien cud cd benh nhan dong nhiem HIV cd xu hudng cao hon cac nghien cud khdng cd benh nhan HIV. Cac phan ti'ch phan nhdm con lai khong cho thay sU khac biet ve ty le gap ADE.

7

Nghien cuu dirgfc & Thong tin thuoc 2017, Tap 8, S6l,trang 2-9

Ban luan Trong nghien cud nay, 69 bai bao da dupe dua

vao tong quan he t hong va phan t ich gpp, vupt t rdi hon han ve so lupng cong t r inh t im kiem ban dau cung nhu bao gom t rong phan t ich cuoi cung so vdi ngh ien cUu cua Shanshan Wu, mo t t ong quan cd p h u o n g phap t u o n g tU dupe t ien hanh vao nam 2012 vdi 39 nghien cUu [7]. Nghien cUu cua Wu da danh gia cac nghien cUu dua tren thang d iem dupe de xuat bdi nhdm nghien cUu "Phan tich ggp cua cac nghien ctfu quan sat" [1], [2]. Thang Newcasle-Ottawa (NOS) dupe s d d u n g t rong nghien cUu cua chung td i g iup danh gia cac nghien cUu mot each toan d ien hon thang d iem t rong ngh ien cUu cua Wu, the hien qua mo t so mat nhU: mdc dp day du cua viec theo ddi , so sanh cac nghien cUu dua t ren th ie t ke [6], [10].

Trong tong so 69 nghien cUu quan sat dupe dUa vao tong quan he thong, cd 39 nghien cUu sif dung phuong phap hoi cUu tU benh an de lay thong t in ve ADE (cac ket qua xet nghiem, ban ghi chep cua nhan vien y te t rong nhdng Ian tai kham dinh ky va mot nghien cUu thu thap ADE tU bao cao t u nguyen cua benh nhan) va 30 nghien cUu t ien cUu cd phuong phap thu thap ADE, t rong dd chu yeu la phuong phap theo ddi t ich cu t (theo ddi d jnh ky) vdi mau bao cao dupe thiet ke san.Tat ca cac bien cd ghi nhan tU cac nghien cUu da dupe chuan hda lai theo thuat ngU WHO-ART [7]. So vdi nghien cUu cua Wu [10], nghien cUu cua chung tdi da tdng hop cac ket qua phan t ich gdp ve ty le xuat hien it nhat mo t ADE nghiem t rpng (26,9%), ty le benh nhan tU vong do ADE (3,2%), day la nhUng con so rat cd y nghia ddi vdi thUc hanh lam sang, d jnh hudng cho cac bac si dieu trj thay thuc sU quan t rpng hon t rong cdng tac theo ddi , danh gia, xd trf va bao cao ADE t rong dieu trj MDR/XDR-TB.

Ty le gpp xuat hien it nhat 1 bien cd la 68,2% tU 7875 benh nhan cua 49 nghien cUu. Rdi loan tieu hda la bien cd bat Ipi phd bien nha't vdi ty le gpp la 39,6% tU47 nghien cUu. NhUng rdi loan khac cung co ty le gdp kha cao dd la rdi loan hong cau (18,8%), rdi loan toan than (18,3%), rdi loan than kinh t rung uong va than kinh ngoai vi (15,2%). C6 the.thay, ty le xuat hien bien cd d benh nhan MDR/XDR-TB la rat cao, vdi khoang mot phan ba t rong so nay (21,8%) can phai thay ddi phac do, anh hudng rat Idn den qua tr inh dieu trj cung nhUchat lUpng song cua ngUdi benh.

Cd nhieu bien cd la phan Ung khdng mong mudn

BAI NGHIEN c a u '

dien hinh cua cac thudc lao hang hai dupe de cap t rong y van da dupe nhieu nghien cUu ghi nhan (> 40/69 nghien cUu) n h u rdi loan than kinh, th inh giac-tien d inh, t ieu hda, da va to chUc dudi cua da, rdi loan tarn than. Mo t so bien cd khac tuy dupe ft nghien cUu ghi nhan hpn nhUng lai la nhUng bien cd bat Ipi nghiem t rpng nhu bien cd tren huyet hoc (rdi loan hong cau, bach cau), rdi loan dien giai (ha kali mau), rdi loan chuyen hoa (tang acid uric), rdi loan ndi t iet (suy giap).Trong do, rdi loan hong cau la mot bien cd bat loi dang chu y va cd ty le kha cao mac du chi dupe ghi nhan t rong 6 nghien cUu. Ket qua nay cho thay sucan thiet phai theo ddi sat sao cdng thUc mau cua benh nhan, dac biet theo ddi t ren nhOng benh nhan dupe chi d jnh phac do chUa cac thudc co ddc t inh tren he tao mau nhu l inezolid.

Mot t rong nhUng han che chu yeu cua ngh ien v cUu nay la chi so bat ddng nhat I2 kha cao, dao ddng

tU61,77% den 97,72%, khien cho ket qua gdp chUa dai dien dupe cho tUng nhdm t rong phan tich gdp. Mac du ty le gdp xuat hien it nha't mo t ADE t rong mot so phan nhdm cu the la cao han cac nhdm khac, phan t ich gdp dudi nhdm cho thay khdng cd sU khac biet dang ke giUa cac phan nhdm nay, cd the tU cac yeu to cd kha nang gay sai lech, v i du nhu cac benh mac kem (suy than, v iem gan, dai thao dudng, . . . ) . Chi so bat ddng nha't cao nhU vay chu yeu do sU khac biet kha rd giOa cac nghien cUu thanh phan, cu the la nhUng khac biet ve phuong phap nghien cUu n h u each d jnh nghia hoac t ieu chi chan doan bien cd bat Ipi/bien cd bat loi nghiem t rpng, each theo ddi va thu thap bien cd bat Ipi (vi du : nghien cUu t ien cUu cd can bp y te dupe dao tao bai ban so vdi nghien cUu hoi cUu dua tren bao cao tU nguyen tU benh nhan); khac biet ve mat lam sang n h u phac do chuan ap dung d tUng qudc gia, yeu to nhan chung hoc, t ieu chi lua chpn benh nhan. . . dan den khac biet Idn ve thong ke. Nguy co t iem tang gay sai lech t rong theo ddi ADE nhu cac bien cd chi ghi nhan theo Idi ke cua benh nhan cung cd the anh hudng den t inh chinh xac cua ket qua nghien cUu. Ngoai ra, nghien cUu gidi han ngudn tai lieu t im kiem tU duy nha't mo t ngudn dU lieu PubMed/Medl ine vdi chien lupc t im kiem sUdung cac tU ddng nghla tren MeSH va chi I pa chpn bai baoTieng Anh do khan hiem ve ngudn lUc khi t iep can vdi cac ngudn tai lieu it dupe chia se rdng rai khac nhu Embase, Google Scholar... Mot han che khac t rong nghien cUu nay la viec chUa thUc hien danh gia th ien vj t rong xuat ban de hudng td i xac

8

Nghien cuti difcfc & Thong tin thuoc 2017, Tap 8, So 1, trang 2-9

BAI NGHIEN CQU

djnh them nhufng yeu to gay bat dong nha't giufa cac nghien cud va kha nang anh hudng den ket qua phan tich gpp. Ben canh do, nghien cUu cung khong the danh gia dope anh hudng cua ADE den ket qua dieu trj do th ieu cac duf lieu can thiet co lien quan do chung toi khong the t iep can sau hon tdi dO lieu gdc cua cac nghien cud va ton t rpng ghi nhan cua tdng bai bao dupe Ida chpn.

Ket luan TO phan tich gdp cho thay ty le xuat hien it nha't

mot ADE la kha cao (68,2%) t rong do ty le gap it nha't

mot ADE nghiem t rpng la 26,9% va ty le tO vong do ADE la 3,2% ( I 2 = 61,77%). Cac bien co tren he t ieu hda la pho bien nha't (39,6%) sau do la bien co tren rdi loan hong cau (18,8%) va cd t inh t rang roi loan toan than (18,3%). Ket qua nghien cUu nhan manh viec can thiet phai theo ddi bieu hien lam sang cung n h u giam sat t inh t rang cua benh nhan thong qua cac ket qua xet ngh iem can lam sang t hudng quy t rong suot qua t r inh dieu trj de tarn soat cac bien co bat Ipi nghiem t rpng cd nguy co xay ra de tU dd cd nhUng can th iep dieu trj phu hop.

T A I L I E U T H A M K H A O

1. Egger Matthias, Davey-Smith George, et al. (2008), Systematic reviews in health care: meta-analysis in context, John Wiley & Sons, pp.336-346.

2. DeyT., Brigden G., et al. (2013), "Outcomes of clofazimine for the t reatment of drug-resistant tuberculosis: a systematic review and meta-analysis", J Antimicrob Chermother, 68(2), pp. 284-293.

3. Jiang R. H., Xu H. B., et al (2015), "Outcomes of Chinese herb medic ine for the t reatment of mult idrug-resistant tuberculosis: a systematic review and meta-analysis", Complement Ther Med, 23(4), pp. 544-554.

4. Langendam M.W.,Tiemersma E.W., et al. (2013), "Adverse events in healthy individuals and MDR-TB contacts treated w i th ant i- tuberculosis drugs potent ia l ly effective for prevent ing deve lopment of MDR-TB: a systematic review", PLOS ONE, 8(1), pp. 53599.

5. Stroup D.F., Berlin J.A., et al. (2000), "Meta-analysis of observational studies in ep idemio logy: a proposal for report ing. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group", JAMA, 283(15), pp. 2008-2012.

6. Wells G.A., Shea B., et al. (2000), The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses, "ht tp: / /www.ohri .ca/programs/cl in ical ep idemio loqy/nos manual.pdf"

7. World Health Organisat ion - The Uppsala Mon i to r ing Centre (2012), WHO Adverse Reaction Terminology- WHO-ART.

8. World Health Organisation. (2015), Global tuberculosis report, pp.66-73.

9. World Health Organisat ion. (2014), Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis pp. 8-9; 18; 76-86; 149; 152-165.

10. Wu S., Zhang Y., et al. (2013), "Adverse Events Associated With the Treatment of Mult idrug-Resistant Tuberculosis: A Systematic Review and Meta-analysis", American journal oftherapeutics, 23(2), pp. 521-30.

*Do khudn kho gidi ban so trang theo quy dinh cua tap chi, danh sdeh day du cac nghien cdu: lien he nhdm tdc gia deed thong tin chi tiet.

(Ngay gUi dang: 13/12/2016 - Ngay duyet dang: 24/3/2017)