B Y T TRNG I HC DC H NI ON TH PHNG THO BC U KHO STCC SAI ST TRONG S DNG THUC V MI LIN QUAN VI BIN C BT LIT C S D LIU BO CO ADR VIT NAM

KHA LUN TT NGHIP DC S H NI 2015 B Y T TRNG I HC DC H NI ON TH PHNG THO BC U KHO STCC SAI ST TRONG S DNG THUCV MI LIN QUANVI BIN C BT LIT C S D LIU BO CO ADR VIT NAM KHA LUN TT NGHIP DC S Ngi hng dn: 1.TS. V nh Ha 2.ThS. Trn Thu Thy Ni thc hin: Trung tm Quc gia v Thng tin thuc v Theo di phn ng c hi ca thuc H NI 2015 LI CM N Ti xin dnh s bit n chn thnh v su sc nht n TS. V nh Ha ging vin B mn Dc Lm Sng, H Dc HN v ThS. Trn Thu Thy cn b Trung tm DI & ADR Quc gia, nhng ngi thy, ngi ch trc tip hng dn, tn tnh ch bo ti trong qu trnh thc hin ti.Ti cng xin by t lng bit n i vi TS. Nguyn Hong Anh ging vin BmnDcl,PhgimcTrungtmDI&ADRQucgia,lngiu tn tm ng m c cho mi nghin cu, ngay t nhng thit k s khai nht n khi hon thnh, l ngi dn ng ng knh cho ti c v cng vic ln tinh thn.Ti xin gi li cm n n em Nguyn Thy Hng lp N1K66, bn Vn Qun, Nguyn Tin Php, Nguyn Minh Trang, Phan Th Anh Th lp N1K65 v s gip nhit thnh v t m. Ti xin cm n DS. Nguyn Hong Anh cn b Trung tm DI & ADR Quc gia, v s h tr thng trc v mt d liu v k thut. Nh c h m nghin cu ny mi c th hon thnh.Tixincmnccanhch cnbcaTrungtm DI&ADRQucgia,v luntoiukinchotitrongqutrnhtinhnhnghincu,tibitrng mnh c th nhn c bt c thng tin v ch dn cn thit no vo bt c lc no.Tixingilicmnnccthycvbnb,ngigiptitrong sut 5 nm hc tp v bc u nghin cu khoa hc trng H Dc HN.Vi ti, h l u nhng ngi ngi thy, ngi bn ng hnh qu bu m tirtmaymnmicc,khngchvsngvin,giptrongqutrnh thc hin nghin cu m c trong chun b cho k hoch hc tp trong tng lai.Cuicng,tixingilicmngianhvngithn,nhngngi lun l ch da vng chc cho ti trong hc tp v cuc sng.H Ni, thng 5 nm 2015 ON TH PHNG THO DANH MC CC K HIU, CH VIT TT K hiu, ch vit tt Thut ng ting VitThut ng ting Anh ADRPhn ng c hi ca thucAdverse Drug Reaction AEBin c bt li ca thucAdverse Event CGDCnh gic dc CSDLC s d liu CSYTC s y t MESai st lin quan n thucMedication error NCC-MERP Hi ng iu phi Quc gia Hoa K v Bo co v phng trnh sai st lin quan n thuc National Coordinating Council for Medication Error Reporting and Prevention pAE Bin c bt li ca thuc phng trnh c Preventable Adverse Event PMPhng php PPmethod SmPCTm tt thng tin sn phmSummary of Product Characteristics STTS th t Trung tm DI & ADR Quc gia Trung tm quc gia v Thng tin thuc v Theo di phn ng c hi ca thuc WHOT chc Y t th gii World Heath Organization WHO ART Thut ng phn ng c hi theo WHO WHO Adverse Reaction Terminology ICD 10 M quc t v bnh International Classification of Disease DANH MC CC BNG STTBngTn bngTrang 1 1.1TiuchcaHallasvcngsnhgikhnng phng trnh c (avoidability) ca bin c bt li 11 2 1.2CctiuchnguynbncaSchumockvThornton nh gi kh nng phng trnh c ca mt AE 12 3 1.3Thang nh gi ca php lng gi kh nng phng trnh c ca mt ADR 14 42.1 Cch xp loi xc nh ME 26 5 3.1 Tuivgiitnhcabnhnhntrongccboco cnhgivboconghingclinquann ME 33 63.2S lng bo co c tng loi ME theo nhm tui34 73.3S bo co nghi ng c ME theo ng dng thuc35 83.4Cc h dc l hay gp sai st trong s dng36 93.5Cc thuc thng gp sai st khi s dng37 103.6T l bo co nghi ng c mi quan h ME AE 43 113.7 PhnbboconghingcmiquanhMEAE theo cc h dc l hay gp nht 44 DANH MC CC HNH STTHnhTn hnhTrang 11.1Quan h gia ME, AE, ADR5 21.1Quy trnh thu thp v phn hi thng tin trong CGD18 31.3 Quy trnh x l bo co ADR ti Trung tm DI & ADR Quc gia 20 42.1Quy trnh nghin cu23 53.1S lng bo co a vo nh gi v phn tch30 63.2 S bo co nghi ng l ME theo loi sai st ghi nhn c (n = 152) 32 73.3 S bo co nghi ng c mi quan h gia ME v AE theo loi ME (n=85) 40 83.4 Mc nghim trng ca AE c bo co theo loi ME (n=85 42 93.5 S bo co nghi ng c mi quan h ME v khng sinhAE (n=64) 46 MC LC DANH MC CC K HIU, CH VIT TT DANH MC CC BNG DANH MC CC HNH T VN ........................................................................................................ 1 CHNG 1.TNG QUAN ................................................................................. 3 1.1.TNG QUAN V SAI ST LIN QUAN N THUC ................................ 3 1.1.1.Sai st lin quan n thuc ........................................................... 3 1.1.2.Mi quan h gia sai st lin quan n thuc, bin c bt li v phn ng c hi ca thuc ......................................................................... 4 1.1.3.Phn loi sai st lin quan n thuc ........................................... 5 1.1.4.Nguyn nhn v cc yu t nguy c dn n sai st lin quan n thuc8 1.1.5.Pht hin sai st lin quan n thuc ........................................... 9 1.2.PHT HIN SAI ST LIN QUAN N THUC T C S D LIU BO CO T NGUYN V BIN C BT LI / PHN NG C HI ............................... 10 1.2.1.Tim nng ca c s d liu bo co t nguyn trong pht hin sai st lin quan n thuc ....................................................................... 10 1.2.2.Mt s phng php pht hin sai st v bin c bt li phng trnh c t c s d liu ...................................................................... 11 1.3.C S D LIU BO CO ADR VIT NAM .................................... 17 1.3.1.Hot dng Cnh gic Duc ti Vit Nam ................................... 17 1.3.2.C s d liu bo co ADR ti Vit Nam .................................... 18 CHNG 2.I TNG V PHNG PHP NGHIN CU ................. 22 2.1.I TNG NGHIN CU ................................................................ 22 2.2.PHNG PHP NGHIN CU ............................................................ 23 2.2.1.Mc tiu 1: Nhn din cc sai st lin quan n thuc t c s d liu Vit Nam ........................................................................................ 24 2.2.2.Mc tiu 2: Nhn din cc sai st lin quan n thuc c mi quan h vi bin c bt li c bo co ................................................. 26 2.3.CH TIU NGHIN CU TNG NG VI MC TIU RA ................. 27 2.3.1.Ch tiu nghin cu tng ng vi mc tiu 1 ............................ 27 2.3.2.Ch tiu nghin cu tng ng vi mc tiu 2 ............................ 28 2.4.PHNG PHP X L S LIU ......................................................... 28 CHNG 3.KT QU ..................................................................................... 30 3.1.NHN DIN CC SAI ST LIN QUAN N THUC ............................. 31 3.1.1.S lng bo co nghi ng c sai st lin quan n thuc .......... 31 3.1.2.Loi sai st ghi nhn c trong cc bo co nghi ng c sai st lin quan n thuc .................................................................................. 31 3.1.3.Thng tin v bnh nhn .............................................................. 32 a, Thng tin chung v tui v gii tnh ca bnh nhn.................... 32 b, Loi sai st ghi nhn c theo nhm tui ...................................... 34 3.1.4.Thng tin v thuc nghi ng c ME ............................................ 35 3.2.NHN DIN CC SAI ST LIN QUAN N THUC C LIN QUAN N BIN C BT LI C BO CO .................................................................... 39 3.2.1.S lng bo co c mi quan h gia sai st lin quan n thuc v bin c bt li ...................................................................................... 39 3.2.2.Phn tch cc sai st lin quan n thuc nghi ng dn n bin c bt li theo loi sai st ........................................................................ 39 3.2.3.Thng tin v AE nghi ng lin quan n ME............................... 41 a. Mc nghim trng ca phn ng trong cc bo co nghi ng c mi quan h sai st lin quan n thuc v bin c bt li .................. 41 b. Bin c (AE) ghi nhn c trong cc bo co c mi quan h ME AE theo h c quan b nh hng ....................................................... 42 c. Thng tin v ni xy ra AE ............................................................. 43 3.2.4.Thng tin v thuc lin quan n sai st c th dn n bin c bt li c miu t ................................................................................. 44 a, Phn b bo co nghi ng c mi quan h gia sai st lin quan n thuc v bin c bt li theo nhm dc l ......................................... 44 b, Sai st trong s dng khng sinh nghi ng dn n bin c bt li .. 46 CHNG 4.BN LUN ................................................................................... 47 4.1.BN LUN V PHNG PHP NGHIN CU ...................................... 47 4.2.BN LUN V KT QU NGHIN CU .............................................. 50 4.2.1.Kt qu v sai st trong s dng thuc ....................................... 50 4.2.2.Kt qu v sai st trong s dng thuc nghi ng c mi lin quan vi bin c bt li c bo co .............................................................. 53 CHNG 5.KT LUN V XUT .......................................................... 57 TI LIU THAM KHO PH LC 1. MU BO CO PHN NG C HI CA THUC PH LC 2: B 20 TIU CH THEO PHNG PHP P CA WHO V CCH I CHIU DNG TRONG NGHIN CU PH LC 3: CC CP THUC C XEM L TRNG LP TR LIU PH LC 4: MU NH GI MI QUAN H GIA ME V AE PH LC 5: BO CO C LOI B KHI DANH SCH ME PH LC 6: CC ME NGHI NG LIN QUAN N AE PH LC 7: CC ME KHNG LIN QUAN N AE PH LC 8: DANH SCH ME PHT HIN C TRONG NGHIN CU1 T VN u tin l khng gy hi (First, do no harm) l cu m u ca li th Hippocrates, cng c xem l tn ch hnh ng trong s nghip bo v v chm scsckhenhndncaminhnvinyt.Tuynhin,nhmtcondaohai li,khngcdcchtnomhontonkhngcphnngchi(ADR Adversedrugreaction),vsaistlinquannthuc(Medicationerror ME)l mt trong nhng ngun gy hi khng ch ln nht cho ngi bnh trn ton th gii[74].Theomtnghincunm2013,tnht210000ngiMtvong mi nm do hu qu trc tip ca ME, a ME tr thnh nguyn nhn gy t vong th ba ti nc ny, ch xp sau bnh tim mch v ung th [33], [72]. Ti chu u, MEvccbincbtlilinquannchmscytxyratrn812%trng hp nhp vin, 23% cng dn chu u tuyn b tng trc tip b nh hng bi ME [63]. Mt nghin cu tng quan ch ra rng 24% vic nhp vin lin quan n s dng thuc, ba phn t trong s ny l phng trnh c [52]. Chi ph pht sinh do ME mt s quc gia c th ln n 6 n 29 t la mi nm [62].ccncangphttrinnhVitNam,khnngmtbnhnhngp bin c bt li trong bnh vin cao hn so vi cc nc pht trin [62]. Mc d d liu v ME nc ta cn hn ch, kt qu t mt s nghin cu bc u cho thy tlMElinquannthchinthuccaiudngdaongt37,7%n 68,6% liu/lt thuc [9], [46].iu kin tin quyt gim thiu ME l xc nh c ME, qua phn tch hon cnh v nguyn nhn h thng dn n sai st. Tuy nhin, nc ta cha c h thng bo co t nguyn dnh ring cho ME, trong khi phng php nghin cu quan st trc tipnh thc hin trong mt s nghin cu trc y li kh trin khai rng ri trong thc t [9], [43], [46].Tnm1999,VitNamgianhpmnglicaTchcGimstthuc ton cu UMC (Upssala Monitoring Centre) [70]. Tnh ring t khi mu bo co v phnngchi(AdverseDrugReactionADR)micabytcpdng, tronggiaion20112014,c20172bocoADRcxlvlutrti 2 Trung tm Quc gia v Thng tin thuc v Phn ng c hi ca thuc [13]. Mc d banutptrungvoADR,ngundliungkthuctccbocot nguynnyngycngthhintimnngcamnhtrongvicphthinvphn tch cc ME [62]. Trong bi cnh , chng ti thc hin ti: Bc u kho st cc sai st trong s dng thuc v mi lin quan vi bin c bt li t c s d liu bo co ADR Vit Nam vi cc mc tiu: 1. Nhn din cc sai st lin quan n thuc t c s d liu bo co phn ng c hi ca thuc.2. Nhn din cc sai st lin quan n thuc c mi quan h vi bin c bt li c bo co. 3 CHNG 1. TNG QUAN 1.1.Tng quan v sai st lin quan n thuc 1.1.1.Sai st lin quan n thuc Hin nay, c rt nhiu nh ngha v ME c s dng trong cc nghin cu khc nhau.nh ngha thng dng v c chp nhn rng ri trn th gii hin nay v saistlinquannthuc(MedicationErrorME)lnhnghacaHing iu phi Quc gia Hoa K v Bo co v phng trnh sai st lin quan n thuc (NationalCoordinatingCouncilforMedicationErrorReportingandPrevention NCCMERP):Saistlinquannthuclbtkbinccthphngtrnh nockhnnggyrahocdnnvicsdngthuckhnghpl,hocgy hi cho bnh nhn trong khi thuc c kim sot bi nhn vin y t, bnh nhn, hoc ngi tiu dng. Cc bin c nh vy c th lin quan ti thc hnh chuyn mn, cc sn phm chm sc sc khe, quy trnh v h thng bao gm: k n v qutrnhchuyngiaonthuc;ghinhn,nggivdanhphp;phach,cp pht v phn phi; qun l, gim st v s dng thuc trn ngi bnh [77]. Gn y, EU a ra mt nh ngha v ME: Mt tht bi khng c ch ch trongqutrnhiutrbngthucdnnhoccnguyc dnntnhicho bnh nhn. nh ngha ny loi tr cc trng hp dng qu liu thuc mt cch c , s dng off lable v lm dng thuc [24]. Hng dn thc hnh tt cnh gic dc (Good Pharmacovigillance Practice Guideline) ca C quan dc phm chu u (European Medicines Agency EMA) nh ngha v ME s dng trong vic h thng bo co ca n l chu u nh sau:Saistlinquannthuclbtcsaistkhngchchnotrongqu trnhkn,phnphihocsdngsnphmytdiskimsotcanhn vin y t, bnh nhn hoc ngi tiu dng [26]. nh ngha ny tp trung vo vic qun l v bo co bin c bt li i vi sn phm y t v khng bao hm ton b cc giai on ca qu trnh s dng thuc, v d nh trong khu pha ch thuc [24].4 Nhvy, ME l c thphng trnh c.yl c im quan trngca ME v c cp trong nhiu nh ngha. Do vy, vic d phng v gim thiu nguy c lin quan n thuc tr thnh mt mc tiu quan trng trong chnh sch an ton thuc ca mi quc gia. Mt khc, ME c th gy hi cho bnh nhn (bin c bt li ca thuc phng trnh c) hoc cha gy hi cho bnh nhn, thm ch ngayckhivicsdngthucsaichactinhnhtrnbnhnhn.iuny cho thy khng cn thit phi c xy ra hu qu c hi trn bnh nhn xc nh mt li l ME. Ngoi ra, mt ME cng c th c nguyn nhn t vic cha gio dc bnh nhn mt cch y v thc hnh s dng thuc ng [43]. nhnghacsdngtrongnghincunylnhnghacaNCC- MERP. 1.1.2. Mi quan h gia sai st lin quan n thuc, bin c bt li v phn ng c hi ca thuc Bin c bt li ca thuc (Adverse Drug Event ADE, hay Adverse Event AE) l nhng tn thng xy ra trn bnh nhn m nguyn nhn c th do thuc gy ra hoc thiu thuc cn thit cho bnh nhn [43]. Phnngchicathuc(ADR)cnhnghatheoWHOlnhng phnngchi,khngnhtrcxuthinkhidngthucliuthngdng cho ngi d phng, chn on, iu tr hoc thay i chc nng sinh l ca c th [5]. Bincbtlicathucphngtrnhc(preventableAdverseEvent pAE):mttnthnglktqucasaistxyratrongbtkgiaionnoca quy trnhs dng thuc [62]. Hintithutng ny c xuhngcthaybng phnng chi phngtrnh c (preventable Adverse DrugReaction pADR), tuynhiniunyihiphimrngnhnghacaADRbaohmthm nguyn nhn t cc sai st lin quan n thuc [62], [65]. Sai st tim tng ca thuc ( VII) l mt hon cnh hay tnh hung c th dnnsaist.Honcnhhaytnhhungnycthlinquanhockhnglin quan n mt bnh nhn c th [25]. 5 Quan h gia cc yu t ny c th hin trong hnh 1.1. Hnh 1.1. Quan h gia ME, AE, ADR [17], [24] Nhn xt: T hnh 1.1 c th thy AE bao gm ton b ADR v cc sai st lin quan n thuc gy hi cho bnh nhn ( (I) v (II)). Trong , cc bin c bt ligyrabiMElnhngbinccthphngtrnhc(preventableadverse drugevents,(III)+(IV))docimcaMElcthphngtrnh.ctnh35% cc ME c th phn loi nh AE [43]. Mt khc, nhng sai st khng gy ra bin c bt li c xem nh bin c bt li tim tng ca thuc (potential adverse drug events hay near miss events, (V)). Trong trng hp ny, c th ME c phthintrckhitcngtrnbnhnhn(ccsaistcngnchn (interceptedMedicationErroriME)hocbnhnhngpMEnhngkhngxut hin AE [42]. 1.1.3. Phn loi sai st lin quan n thucCnhiucchphnloiMEkhcnhaudatrncccchtipcnkhc nhau. Trong , phn loi ME theo yu t dn n sai st, theo giai on xy ra sai st v theo mc nghim trng ca sai st l nhng cch phn loi c ngha v c p dng rng ri hn c trong vic pht hin, nh gi, phn tch v d phng ME.a, Phn loi theo yu t dn n sai st PhnloiMEtheoyutdnnsaistlcchphnloicsdng ph bin nht. Di y l 12 phn loi sai st theo Hi Dc s Hoa K trong h thng Y t (ASHP). 6 Sai st k n: sai st trong la chn loi thuc (da vo ch nh, chng chnh,tinsdng,thucangiutrvccyutkhc),liulng,dng bo ch, s lng, ng dng, nng , tc a thuc, hoc hng dn s dng thuc ca mt thuc c k n bi ngi k n hp php; sai st do n thuc khng c c; Sai st do thiu thuc: bnh nhn khng c dng loi thuc c k n; Sai thi gian: bnh nhn dng thuc ngoi khong thi gian cho php theo liu trnh dng thuc; Saidos dngthuccha cphp: Sdngloithuckhngc k n cho bnh nhn ; Sai liu: bao gm dng qu liu, thp hn liu iu tr, qun liu, a thm liu khng ng nh ch nh hoc khng nh liu dng cho bnh nhn; Saidngboch:dngchobnhnhnloithuckhngngdngbo ch c k n; Sai trong chun b thuc: thuc c phach hoc thao tc khng ng trc khi s dng; Saikthutdngthuc:quytrnhkhngphhphockhngngk thut s dng thuc; Sai khi dng thuc bin cht: dng thuc ht hn hoc h hng; Saitronggimst:thiusttrongvicnhgichiutrvpht hin cc vn trong s dng thuc hoc khng s dng d liu lm sng hoc xt nghim ph hp nh gi y p ng ca bnh nhn vi thuc c k n; Saitrongtunthiutr:bnhnhnthiutunthiutrvithuc c k n; Sai st khc: nhng sai st khng phn loi c theo cc nhm trn [49]. b, Phn loi theo giai on xy ra sai st trong quy trnh s dng thuc Theo phn loi ny, cc ME c th xy ra trong cc giai on sau: Mua thuc; 7 Bo qun thuc; K n; Sao chp n thuc v phin dch thng tin; Pha ch, chun b thuc; Phn pht thuc; Dng thuc cho bnh nhn (bao gm c vic kim tra xc nh thuc); Gim st bnh nhn trc v sau khi dng thuc [43]. c,Mtscchphnloitheomcnghimtrngcahuqulmsngtrn bnh nhn Trong hng dn v gim st ME, Hip hi Dc s Hoa K trong h thng y t khuyn ngh cn c nh gi v mc nghim trng v ngha lm sng tim nngcaccMEphthin[49].Mtcchnginnht,saistcthphn thnh 2 loi: (1) c ngha lm sng (bao gm nhng sai st c kh nng gy t vong hoc bnh l nng, s ai stc kh nng nghim trng v sai st c kh nng ng k); hoc (2) nh [19], [40]. Cch phn loi theo NCC MERP pht trin t cch phn loi ca Hartwig, Denger v Schneider [31] gm tm mc nghim trng t A n I nh sau: Khng c sai st oA - Tnh hung hoc s kin c nguy c dn n ME; Sai st nhng cha gy hi oB - ME xy ra nhng cha nh hng n thc hnh thuc trn bnh nhn; oC - ME xy ra trn bnh nhn nhng khng gy hi; oD - ME dnncntngcnggimstbnhnhn hoc cnccbin php can thip m bo an ton cho bnh nhn; Sai st gy hi oE-MEdnngyhinhtthitrnbnhnhnvihiccbin php can thip; 8 oF - ME dn n gy hi nht thi trn bnh nhn dn n cn thit phi nhp vin hoc ko di thi gian nm vin; oG - ME gy tn hi vnh vin cho bnh nhn; oH - ME dn n cn cc bin php can thip m bo tnh mng cho bnh nhn; Sai st dn n t vong oI - ME dn n t vong trn bnh nhn [78]. Ngoira,MEcncphnloitngtnhcchphnloimc nghimtrngcabocoADR,baogmnghimtrngvkhngnghimtrng [49], [55]. 1.1.4. Nguyn nhn v cc yu t nguy c dn n sai st lin quan n thuc Thitkcaquytrnhhayhthngytcvaitrquantrngtrongkim sot nguy c xy ra cc sai st v bin c bt li gy ra trn bnh nhn, v pha sau huhtccsaistcnhnlmthaynhinlivmththng[43].Nicch khc,chbngcchnhnnhnnhngthiustcahthng,chngtamicth xc nh nguy c xy ra sai st tng t trong tng lai [36]. T , vn cn lu khixcnhnguyn nhnME lvicaigyrakhngquantrngbngvictm hiu ti sao v bng cch no xy ra ME . Trn c s phn tch cc yu t nh hng n s dng thuc, c th tm tt cc nguyn nhn gy ME nh sau: Thiu thng tin v bnh nhn; Thiu thng tin v thuc; Tht bi trong giao tip v lm vic nhm gia cc nhn vin y t; Nhn thuc, bao b v tn thuc d gy nhm ln; Tiu chun ha, bo qun v phn phi thuc khng an ton; Dngc,phngtinchiathuckhnghonthin,khngantonhoc khng theo tiu chun; Yu t mi trng v m hnh nhn vin khng m bo cho s an ton; nhhng,otolintc,cngtcgimstchayvnnglc ca nhn vin cn hn ch; 9 Gio dc bnh nhn v thuc v ME khng y ; Cha c vn ha v h tr cho an ton thuc, tht bi trong vic hc t cc sai st trc y hoc tht bi hay thiu cc chin lc gim thiu sai st [43]. 1.1.5. Pht hin sai st lin quan n thuc Sau y l mt s cch tip cn thng c s dng pht hin ra ME: T boco giutn: ngi phm phi hoc chngkinsai stboco ME mt cch giu tn. K thut ny c u im l khng tn km chi ph v trnh c lo ngi t pha nhn vin y t. Tuy nhin, ging nh c s d liu (CSDL) bo co ADR, cc bo co ME t hn nhiu so vi con s thc t [7], v nu ADR ch c bo co khi ngi bo co nhn bit c ADR th ME cng ch c bo co khi bn thn ngi bo co nhn bit c ME [22], [53]. Quan st trc tip: ngi quan st c o to i theo iu dng chng kin qu trnh chun b v dng thuc, sau ghi chp li thng tin v i chiu vi y lnh hoc y vn. u im l tnh hiu lc cao, khng b nh hng bi nhn thc, tm l v tr nh ca ngi thc hnh thuc. Nhc im l tn nhiu cng sc v chi ph, i hi ngi quan st phi cng bng v t nh [22], [53]. T boco bin c btli: bo co (v d nh bocoADR)mangtnh php l c vit bi nhn vin y t ti bnh vin, gip pht hin cc sai st thc s gy hi trn bnh nhn. u im ca cch tip cn ny l chi ph khng cao v c th tin hnh trn din rng, tuy nhin cng c hn ch l lun cho kt qu thp hn t l sai st thc t (do khng phi tt c cc AE u c bo co) [22], [53]. y l cch tip cn c s dng trong nghin cu ca chng ti. Phntch binc nghim trng: phntchtptrung vocc AEnghim trngtmnguynnhnsvic.Cchlmnycuimlgipnhgitt hnvnguynnhnsaistnhngphthucnhiuvotrnhcangic phng vn [22]. Tng hp h s bnh n: tng hp bnh n thng c tin hnh bi mt nhm nhn vin y t c o to c bit [22]. Cch lm ny cho php phn tch su v nguyn nhn sai st v pht hin c c nhng ME khng thng pht hin 10 cthngquaccphngphpkhc[43],tuynhinihinhiucngscv khng c ng dng rng ri bn ngoi mi trng nghin cu. Gim st da trn my tnh hay cng c pht hin bin c (AE trigger tool): pht trin t phng php tng hp h s bnh n, nhng s dng phn mm kim tra cc y lnh v kt qu cc xt nghim lin quan n ME hoc AE [21]. Cng ging nh phng php trn, cch tip cn ny pht hin c c nhng ME thngkhngphthincthngquaccphngphpkhc,tuynhinchn chlngaycnhngtrungtmccsbnhndliuint,tCSDLcho php tm kim vn bn hoc cung cp ty chn ny [22], [43], [53]. 1.2.Pht hin sai st lin quan n thuc t c s d liu bo co t nguyn v bin c bt li / phn ng c hi 1.2.1. Tim nng ca c s d liu bo co t nguyn trong pht hin sai st lin quan n thuc Bo co t nguyn l phng php ch yu theo di v pht hin ADR, c s dng rng ri trn ton th gii. H thng bo co t nguyn l h thng thuthpccboconlvADRvccvndlinquandnsdngthuc, c cc cn b y t cng nh cc cng ty sn xut kinh doanh dc phm bo co mt cch t nguyn v c quan c thm quyn qun l v ADR [15], [58].Mcchchnhcahthnglphthincctnhiuvtnhantonca thuc, a ra gi thuyt v cung cp nhng thng tin quan trng v nhm i tng nguy c v cc yu t nguy c [51], [58]. Cc tn hiu ny sau s c nh gi, phntchvkimchng. Trncs,cquanqunlctharaccquyt nhphhpvithucnhmmboantonchongibnh[15].Mcdcn nhiu hn ch, bo co t nguyn vn c xem l hot ng ct li nht trong h thng cnh gic dc (CGD) [44].Triquathigian,hthngbocoADRngycngchothytimnng ca n trong vic pht hin nhngtn hi cho bnh nhn do mt sai st trong quy trnh s dng thuc. Nhng sai st gy ra tn hi ny c th c th hin mt cch tnh c hayc trongbo co ADR. WHO cng xc tin vic m rng vai tr 11 ca cc trung tm CGD vt ra ngoi lnh vc mc tiu ban u l theo di ADR. Gn y, d n Theo di Dc phm (the Monitoring Medicines project) ca WHO vi ngun qu t y ban chu u xem xt li cc thng tin thng c trong mt bocotnguynvxutsai,bsungmtsthngtingipchchovic xcnhccME[61]. nhiutrungtmCGDtrnthgii,hthngboco t nguyn hin khng ch thu thp cc bo co thun ty v ADR theo nh ngha c m cn ghi nhn cc bo co nghi ng cht lng thuc v ME [42]. 1.2.2.Mt s phng php pht hin sai st v bin c bt li phng trnh c t c s d liu Mt s nghin cu trn th gii v pht hin ME v pAE (AE lin quan n ME)tCSDL(trongbaogmCSDLbocoADR)ctinhnh.Tuy nhin cc nghin cu ny s dng cc b tiu ch nh gi rt khc nhau: Cng c ca Hallas v cng s [30] Bng 1.1. Tiu ch ca Hallas v cng s nh gi kh nng phng trnh c (avoidability) ca bin c bt li [30] Hon ton trnh c (definitely avoidable) Bin c xy ra do vic iu tr bng thuc hoc khng ph hp vi hiu bit hin ti v thc hnh y khoa hoc r rng khng thc t, trong xem xt dn cc hon cnh bit. C th trnh c (possibly avoidable) Khng c sai st trong vic k n, tuy nhin c th trnh cbincnunhnvinyttinhnhmtnlcvt quccyucuthngquy(aneffortexceedingthe obligatory demands). Khng trnh c (not avoidable) Bin c khng th phng trnh c bi bt c phng tin hplno(anyreasonablemeans),hocbinckhngd onctrc(unpredictableevent)trongqutrnhiu trhontonphhpvithchnhykhoatt(good medical practice). Khng nh gi c (unevaluable) Khng thu thp c d liu cn thit phn loi hoc cc bng chng khng thng nht. 12 Cng c ny da trn mt tiu ch chung chung phn ng s khng xy ra nucn b nhnvin yt s dngccbinphp phngtrnh phhp,phnloi phng trnh c c trnh by trong bng 1.1 [30]. CngccaHallascuimlchophpnhgichungtonbqu trnh iutr v khng loi tr bt c mt nguyn nhn no dn n tnh phng trnh c, iu c th xy ra nu s dng mt b tiu ch chi tit nh trc, mt khc cng cho php phn tch loi sai st theo b thut ng v phn ng bt licathuccaWHO(WHOAdverseDrugReaction-WHOART)[42]. Nhc im caphng php ny lphthucnhiu vo nginhgido t a ra cc gi v sai st c th xy ra hoc cn lu . Cch nh gi ny c sdngtrongnghincucaLovborgvcngs(2012)trnccADRc bocoThyin[42]vnghincucaTemplevcngstrnnhikhoa (2004) [56]. B tiu ch ca Schumock v Thorton v cc bin th ca n Bng 1.2. Cc tiu ch nguyn bn ca Schumock v Thornton nh gi kh nng phng trnh c ca mt AE [54] Bin c c nh gi l phng trnh c nu c nhiu hn hoc bng mt cu tr li c cho cc cu hi sau y: 1. Thuc c lin quan n ADR khng c nhn nh l ph hp vi tnh trng lm sng ca bnh nhn? 2. Liu dng, ng dng v tn sut s dng thuc khng ph hp vi tui, cn nng v mc bnh l (disease state) ca bnh nhn? 3. Cc theo di iu tr yu cu hoc cc xt nghim lm sng cn thit khc khng c tin hnh? 4. Bnh nhn c tin s d ng hoc phn ng vi thuc c s dng? 5. Phn ng c lin quan n mt tng tc thuc? 6. C ghi nhn c nng thuc ngng c tnh trong huyt tng? 7. Phn ng c lin quan n vic bnh nhn km tun th? 13 Trong cc nghin cu v sau, b tiu ch ny c iu chnh mt s imnhgicmtcchtondinhn.Cth,trongnghincuca Dormann v cng s (2004), trong trng hp Khng c mt cch iu tr thay th khc (v d trong trng hp thuc ung th) hoc li ch ca vic iu trvi thuc gy ra bin c ln hn nguy c th vic xy ra cc AE c nh gi l c th chp nhn c [85]. Ducharme v cng s (2006) li iu chnh tiu ch s 4 nhgitrntinsdngcacnhmthucchkhngchtrnthuc,mt khctiuchth6cpncccktquxtnghimthhinctnhca thuc, v d nh nng K+ trong mu tng cao [84]. B tiu ch ny c s dng trongnghincuvctnhphngtrnhccaAEcaGholamivcngs (1999) [27] v nghin cu v sai st trong s dng thuc ca Tanti Ami v cng s (2013) [55] t c s d liu bo co ADR. Thang nh gi kh nng phng trnh c ca Php c a ra bi Imbs v cng s (1998) [66], sau c pht trin bi Olivier v cng s (2005) [48] Sau khi nh gi tng mc (xem bng 1.3), tng im thu c nm trong khong t -11 n +18. Trong cch nh gi nguyn bn ca Imbs v cng s, tng im dng girngADR lphng trnh c vngc li vi tng im m. Cch nh gi ca Olivier v cng s chi tit hn vi 3 phn loi: hon ton khng phng trnh c nu im tng -2, c tim nng phng trnh c nu im tngnmtrongkhongt-1n+8vhontonphngtrnhcnuim tng +9. Thang im ny c u im l kh chi tit tuy nhin cn cn xem xt v cch phn b im s cho cc tiu ch cng nh rt gn li cc tiu ch khng cn thit, mt khc tin cy gia cc chuyn gia nh gi cn thp (0,11) [48]. CchnhgicaOlivierdatrnthangimnycpdngtrong nghin cu v AE ca thuc gim au trn CSDL CGD thc hin bi Cazacu Irina v cng s (2015) [20]. 14 Bng 1.3. Thang nh gi ca Php nhm lng gi kh nng phng trnh c ca mt ADR [66] im Thuca Kinthcvthucvvaitrcthccathuctrongvicxuthin ADR: L gi thit, cn tranh ci+1 L vn ng lo ngi, c nu ra rng ri bi cc bi vit hoc nghin cu ang tin hnh +2 Mi quan h nhn qu c lm r+3 Truyn thng v vn ny Khuyn co l v hi0 Lo ngi+2 ng lu v nguy c+3 Bnh nhn Ca lm sng: cc yu tnguy c Khng c yu t nguy c0 Yu t nguy c kh xc nh+2 Yu t nguy c d xc nh+3 S dng thuc Tun th tthockhngc cc khuyncov tunth/thntrngng vai tr no trong vic xy ra ADR 0 Bnh nhn gp kh khn trong tun th iu tr+2 Khng tun th cch s dng thuc d c p dng, c th do bnh nhn hoc ngi k n +3 K n iu kin k n Bt buc phi k n cho bnh nhn-12 Vic k n c th khng hp l nhng chp nhn c-4 15 Khng cn thit hoc chng ch nh+3 X l tc dng khng mong mun Tt : ngn chn hoc gim tc dng khng mong mun0 Khng hp l+2 Khng x tr, lm tng nng tc dng khng mong mun+3 a. Vic lng gi ny ch xem xt nhng kin thc v thng tin c sn thi im xy ra phn ng, c tnh n cc d liu lm sng c sn ca bnh nhn thi im ny. oS dng thut ng v phn ng c hi ca thuc ca WHO B thut ng WHO-ART c sn cc phn bc v 4 mc khc nhau: H cquanbnhhng(SystemOrganClass-SOCmc1),thutngmc nng (High level term, HLT, mc 2), thut ng u tin (Preferred term- PT, mc 3),thutngbaohm(Includedterm-IT,mc4).Ccthutngmc nng HLT v vn lin quan n ME bao gm 38 thut ng bao hm IT. Nh vy, bo co ADR nhn c s c nh gi xc nh cc thut ng ny, ng thi xc nh c s c mt ca ME v loi ME. Cch nh gi ny gp nghin cu ca Yeonju Woo v cng s (2014) [64], thch hp vi quy trnh x l bo co ADR Hn Quc. o nhgidatrnbntmttctnhsnphm(Summaryof Product Characteristic SmPC) Mt s nghin cu s dng SmPC nh mt tiu chun xc nh kh nng phng trnh c ca ADR hay ME. Vic s dng thuc khng ph hp vi SmPC chothyME xyra[34] [55]. Vic nhgi nyphthucvou nhc im ca bn thn SmPC nh c thng tin chi tit nhng cha thng nht, khng r rng v khng hu ch [86] [87]. Mt s nghin cu p dng quy trnh nh gi kt hp gia so snh vi SmPC v vic r sot cc trng hp m vic s dng thuc l off label hoc khng c thuc tt hn thay th hoc cn nhc n tnh hnh dch t c bit [34].16 Mt s b tiu ch c kim tra mc ng thun, tuy nhin rt kh nh gi chnh xc, nhy v c hiu ca cc b tiu ch ny [29]. Do , rt kh so snh t l pht hin ME gia cc nghin cu, thm ch khi tin hnh trn cngmt loi CSDL. Nhnthyvic thiumt btiu ch chunnhgi kh nng phng trnh c ca AE, d n Theo di Dc phm ca WHO pht trin mt phng php mi da trn cc tiu ch phng trnh c, gi l phng php P (P-method, PM), c thit k c bit pht hin ME mt cch h thng t cc bo co ca n l v AE/ADR [18], [62]. Phng php P Phng php ny c th p dng cho bt c mt AE no c bo co khi mi quan h gia phn ng v thuc nghi ng c xc nhn thng qua nh gi mi quan h nhn qu [62].PhngphpPchophpnhgitonbqutrnhsdngthuctk n n theo di bnh nhn, nhm pht hin bt c nguy c no c th gia tng t l gpAE/ADR[62].Ccnguycnycuthnh20tiuchdngnhgikh nng phng trnh c ca AE (Ph lc 2) bao gm: cc yu t nguy c lin quan nthchnhnghnghip(ProfessionalpracticePr)ngvicctiuch1n 16; hnh vi ca bnh nhn (Patient Pa) ng vi cc tiu ch 19, 20; v cht lng thuc (Product Pd) ng vi cc tiu ch 5, 6, 17 v 18. Ngi nghin cu tin hnh tr li c, khng, khng r v khng p dng c cho 20 cu hi v mi AE. Mi nguyn nhn ca AE c th tng ng vi nhiu tiu ch khc nhau, v d khi nguyn nhn gy AE l vn v liu, cc tiu ch lin quan cn xem xt l 1, 2, 3, 4, 9, 10, 12, 13 v 16. Nu nguyn nhn ca AE lin quan n thi gian, cn lu n cc tiu ch 3, 4, 7 v 15 [18], [62]. Mttiuchcchnlkhngpdngcnunhsaistkhng thc s nh hng n AE (v d nh vic dng ng thi 2 thuc vi thnh phn tngtkhnglinquannkhnngxuthinphnngdng).Mttiuch c chn l khng nh gi c nu khng c thng tin hoc thng tin khng nh gi (v d nh phn ng d ng khng sinh nhm penicillin nhng khng 17 c thng tinvtins d ng), hoc trnghp mcc thngtin t tiliuc s muthun(vdnhmtthuccdngrngritrntremdkhngcch nh trn bnh nhi) [18]. Mibocosaucnhgilphngtrnhc,khngphng trnh c v khng nh gi c, theo quy c nh sau: MtAEcnhgilphngtrnhcnutnhtmttiuch cxcnh.Tiuchnyc thgnvi:Thchnhnghnghipprofessional practice (Pr), cht lng thuc Product (Pd) hoc bnh nhn Patient (Pa). Mi AE c th c lin quan n mt vi tiu ch. AE c nh gi l khng phng trnh c nu khng c tiu ch no c xc nh. AE c nh gi l Khng nh gi c nu nh c bt c mt tiu ch no l khng r [18].NghincunhgitincycaPMchothyngthungiacc chuyn gia mc kh ng thun (fair), tng t vi mc ng thun trong cc nghin cu khc xc nh pAE thng qua s dng mt b tiu ch nh trc, v dnhbtiuchcaSchumockandThorntonhaybtiuchPhp[15],[16], [19], [48].1.3.C s d liu bo co ADR Vit Nam 1.3.1. Hot dng Cnh gic Duc ti Vit Nam Nm1994,TrungtmtheodiADRHNicthnh lp,mucho cng tc theo di ADR Vit Nam. Nm 1998, Vit Nam tr thnh thnh vin th 56 ca H thng gim st thuc quc t ca T chc y t th gii. Nm 2009, Trung tmqucgiavThngtinthucvPhnngchicathuc(TrungtmDI& ADR Quc gia) c thnh lp v k t nm 2010, trung tm bt u hot ng thu nhn, x l, thm nh v lu tr tt c cc bo co ADR t nguyn c gi v t cc c s iu tr v cc n v khc trong c nc [70]. Cc thng tin tng hp v phn tch c t cc bo co ADR c phn hi cho c quan chc nng v c s ytcnhngbinphpphhpnhmmboantonchobnhnhn.Mt 18 khc,dliuthuctccbocotnguyncngcmhavgin Trung tm theo di Uppsala (xem hnh 2.1). Hnh 1.2. Quy trnh thu thp v phn hi thng tin trong CGD [12] Ch thch: UMC: Trung tm theo di Uppsala (Uppsala Monitoring Centre). 1.3.2. C s d liu bo co ADR ti Vit Nam Ccboco ADR t nguync thu nhn,xl v lu tr to thnh c sdliubocoADR.SlngbocoADRtnguynnhnctiTrung tm DI & ADR Quc gia tng ln ng k trong vng hn 10 nm qua, t 717 bo conm2003n6013boconm2013[70].Chtnhringnm2014,Trung tmDI&ADRQuc giavTrungtmDI&ADRkhuvcTP.HChMinh tip nhn v x l tng cng 8513 bo co (t 94,9 bo co/1 triu dn, gn bng 50%sovitltiuchuncahthngCGDchiuqucaWHOl200bo co/1 triu dn). Trong s , c 98,8% bo co lin quan n ADR, 0,1% bo co lin quan n cht lng thuc v cha c bo co c ch ch v ME [13]. 19 MibocoADRbaogm4nhmthngtinchnh:thngtinvbnh nhn,thngtinvthucnghing,thucdngngthi,thngtinvADRv thng tin v ngi bo co (Ph lc 1) [5]. MtsnghincutinhnhnhgichtlngbocoADRtrong CSDL Vit Nam. im cht lng bo co trung bnh trong ba nm 20112013 mc tng i cao (u mc > 0,8). T l bo co tt mc cao (khong 70%). Tuynhin,vncnmttlngkccbocothiuccthngtincnthit. Nghin cu nh gi cc bo co nhn c nm 2013 cho thy c 17,6% bo co thiu thng tin v liu dng; 13,3% bo co thiu thng tin v thi gian; 12,4% bo co thiu thng tin v hu qu ca ADR; 11,5% bo co thiu thng tin v ch nh; tuivgiitnhcabnhnhnkhngcbocotrong2,7%v4,2%boco [8]. QuytrnhxlbocoADRnhnctiTrungtmDI&ADRc trnh by trong hnh 1.3. Saukhithunhn,bocoADRscccchuynvincatrungtm phnloithnhboconghimtrng(baogmbocokhn)vbocokhng nghim trng theo tiu ch sau: Bo co khn bao gm bo co ADR dn n hu qu t vong; e da tnh mng, can thip x tr nhng ngi bnh cha hi phc; e da tnh mng, ngi bnh ang hi phc nhng phn ng xy ra thnh chui vi mt thuc hoc mt l thuc trong mt thi gian ngn (3 bo co tr ln). Bo co nghim trng c xc nh l khi ADR dn n t vong; e da tnh mng; buc ngi bnh phi nhp vin iu tr hoc ko di thi gian nm vin ca ngi bnh; li di chng nng n hoc vnh vin cho ngi bnh; gy d tt bm sinh thai nhi; hoc bt k ADR c cn b y t nhn nh l gy ra hu qu nghim trng v mt lm sng [12]. Bo co thng: l cc bo co khng thuc hai loi trn.20 Hnh 1.3. Quy trnh x l bo co ADR ti Trung tm DI & ADR Quc gia [12] Saukhisbphn loi,bococginccchuyngiathmnh. Chnh(ldodngthuc)cphnloitheomquctvbnhICD10 (International Classification of Disease). ADR c phn loi theo Danh php phn ng c hi ca thuc WHO ART (WHO Adverse Reaction Terminology). Mi quan h nhn qu gia thuc c nh gi theo 6mc ca thang WHO: 1 Chc chn;2Ckhnng;3Cth;4Khngchcchn;5Chaphnloic;6Khngthphnloic.Trongtrnghpboconghimtrng,bcny c thc hin bi chuyn vin ca Trung tm DI & ADR Quc gia. Trong trng hp bo co khn, mi quan h nhn qu gia thuc c u tin nh gi trc khi tin hnh tra cum ICD 10 v danh php WHO ART hon thin bin bn thm nh [12].Bo co tng kt (qu, nm) Bo co ADR BC khng nghim trng BC nghim trng Kt qu thm nh 3 ln Kt qu thm nh c lp BC khn Kt qu thm nh ln 2 v 3 Phiu phn hi c nhn bc Kt qu thm nh ln 1 Kt qu tng hp (qu, nm) 21 Nh vy, sau khi c x l v thm nh, bo co c nh gi li thng tin v mc nghim trng ca ADR v c thm thng tin v thut ng ting Anh ca ADR, mi quanh nhn qugiathucv ADR, tngtcthuc(nu c)v cc kin nh gi khc ca chuyn gia v bo co. Mcdcnmts hnchvchtlngthngtin,CSDLbocoADR nythhinkhnngcamnhtrongvicphthintnhiucnhgicdc thngquanhiunghincutrnmtthuccthnhallopurinol[2],ceftriaxon [10] hoc mt nhm thuc c th nh thuc cn quang cha iod [11] v thuc iu trlao[6].Nhngnghincuvtnhiucnhgicdcvmtphnngcth cng ang c tin hnh. Thng tin t CSDL Vit Nam c m ha v gi n CSDL CGD VigiBase ca Trung tm gim st Uppsala cng gip pht hin cc tn hiu v thuc ADR. 22 CHNG 2. I TNG V PHNG PHP NGHIN CU 2.1. i tng nghin cu BocoADRtnguynccnbytticccskhm,chabnh givTrungtmDI&ADRQucgia.Mibocobaogm4nhmthngtin chnh: thng tin v bnh nhn, thng tin v thuc nghi ng, thuc dng ng thi, thng tin v ADR v thng tin v ngi bo co (Ph lc 1) [5]. Sau khi c x l vthmnh,bococnhgilithngtinvmcnghimtrngca ADR v c thm thng tin v thut ng WHO ART ca ADR, mi quan h nhn qu gia thuc v ADR, tng tc thuc (nu c) v cc kin nh gi khc ca chuyn gia v bo co [12]. Mc d c tn bo co ADR, nhng bo co ny thc cht lccbo co v bin c btlica thuc AEm ngi boconghi ng l ADR (suspected adverse drug reaction). V vy, trong nghin cu ny, cm t AE c s dng thay cho cm ADR khi cp n ADR c m t trong cc bo co. Tiuchunlachn:boconhnctrongkhongthigiant 16/12/2013 n ngy 16/02/2014. Tiu chun loi tr:oBocolinquanncctrnghptt,thtestphnngkhng sinh, bo co trc tip v vn cht lng thuc, bo co c quy kt mi quan hthucAE/ADRlkhngchcchn,chaphnloicvkhng th phn loi c (gi chung l bo co khng phi v AE); oBocokhngthngtinnhgi:gmccbocokhngc thng tin v bin c bt li v/hoc thng tin v hot cht s dng v/hoc thng tin v l do s dng thuc; oBo co m tt c cc thuc nghi ng gy ra phn ng u khng c ti liuichiutrongdanhmctiliuichiuxcnh(thamkhomc 2.2.1).23 2.2. Phng php nghin cu M t hi cu d liu.Quy trnh nghin cu c m t trong s sau: Hnh 2.1. Quy trnh nghin cu Ly mu nghin cu Bo co nhn c t 16/12/2013- 15/2/2014 Bo co khng phi l AE; Bo co khng thng tin nh gi; Bo co khng c ti liu i chiu cho bt c thuc nghi ng no. Phn tch cc bo co nghi ng c ME (Bao gm bo co c v c th c ME) Loi bo co theo tiu chun loi tr Nghin cu vin so snh vic dng thuc vi ti liu i chiu bng phng php PM Ly kin chuyn gia Cc chuyn gia nh gi mi lin quan gia ME v AE ( Phn tch cc bo co nghi ng c mi lin quan ME v AE (Bao gm c v c thc mi lin quan) Bo co khng pht hin ME Bo co khng quy kt l c ME Bo co khng c mi lin quan ME-AE Mc tiu 1 Mc tiu 2 Chn mu 24 2.2.1. Mctiu1:Nhndinccsaist lin quannthuctcsdliu Vit Nam Saukhicchnvonghin cu,ccbocoADRcnhgipht hinMEbngcchichiuccthngtinvsdngthuctrnbocoviti liu i chiu theo b 20 tiu ch PM ca WHO (Ph lc 2).Qu trnh nh gi c thc hin theo 3 bc nh sau: Bc 1: nh gi tng tiu ch: Nghin cu vin i chiu vic s dng thuc c ghi trong mi bo co vitiliunhtrc,saunhgimitiuchtheo4lachntrlil c, c th, khng v khng p dng c. Cch nh gi ny c thay i so vi nguyn bn trong phng php P ca WHO: mi tiu ch c phn loi l c, khng, khng r v khng p dng c Chuyn lun thuc lm ti liu i chiu c xem xt ln lt theo th t u tin sau: oChuyn lun trong Vidal 20142015 Vit Nam [7]/Mims Online [68] ca bit dc c bo co; oChuyn lun trong Vidal 20142015 Vit Nam [7]/Mims Online [68] ca bit dc gc c cng hot cht, dng bo ch vi bit c c bo co. Cc bitdcnyclytDanhmccngbBitdcgctt1t11 BYT [69]; oDc th quc gia Vit Nam 2009 [3]; oTmttthngtinsnphm(SPC)tiAnh[73],Php[83]vM[80] ca bit dc c cng hot cht, dng bo ch vi bit c c bo co; oMicromedex 2.0 [71]. i vi thuc phi hp nhiu hot cht, nu khng c thuc cng hot cht, dng bo ch v t l phi hp trong danh sch trn c xt l khng tm thy ti liu i chiu. i vi thuc nghi ng l khng sinh, tiu ch s 8 sai ch nh c nh gi da trn nguyn tc sau:25 oTr li c (ch nh c nh gi l khng ph hp) trong trng hp khngsinhlchngchnhtrnbnhnhnv/hocthngtintrnboco khng cho thy nguy c nhim khun; oTrlicthtrongtrnghpkhngsinhkhngphilchngch nh trn bnh nhn v thng tin trn bo co cho thy c nguy c nhim khun nhng khng r bnh nhn c thc s c nhim khun hay khng; oTrlikhngtrongtrnghpkhngsinhsdngkhngphil chng ch nhtrn bnh nhn v thng tin trn bo co cho c xut hin nhim khunv/hocldodngthucnmtrongccchnhcachuynlunthuc dng i chiu.Tiu ch s 12 c iu chnh t tng tc thuc-thuc nh nguyn bn caPMthnhtngtcthucnichungvcnhgiphnmm Stockleys Drug Interaction Checker [67] theo 4 mc tng tc: oTr li c nu c tng tc mc 1 e da tnh mng hoc chng ch nh; oTr li c th nu khng c tng tcmc 1 v c tng tcmc 2 cn chnh liu hoc theo di cht ch; oTrlikhngnukhngphthintngtchocchctngtc mc3:arahngdnvcctcdngkhngmongmuncthgp v/hoc cnnhcmts theodihoctng tcmc4: khngctng tc c ngha lm sng. Tiu ch s 13 v trng lp tr liu c nh gi bng cch xem xt tt c cc thuc c cng thi gian s dng c ghi nhn trong bo co. Bo co c xc nh l c trng lp tr liu nubnh nhn c dng ng thi hai thuc c cng hot cht hoc mt cp hot cht cng ch tc dng c trong danh sch Trng lp trliukhngcnthit(Unnecessarytherapeuticduplication)caHomeHealth Centre (Ph lc 3) [75].26 Tiuchs20vbnhnhntdngthuckncnhgibng cch i chiu vi Danhmc thuc khngk n, ban hnh km theo Thng t 08/2009/TTBYT ca B Y t ngy 01 thng 7 nm 2009 [4].Bc 2: Xp loi bo co Sau khi tng hp kt qu cc cu tr li, bo co c xp loi l bo co nghi ng c ME hoc bo co khng c ME theo tiu ch t ra trong bng 2.1: Bng 2.1. Cch xp loi xc nh ME Xp loi bo coTiu ch Nghi ng c ME Khng nh c ME C cu tr li l c mt hoc nhiu tiu ch.Mi tiu ch nh vy c tnh l mt ME.C thc ME Ch c cu tr li l c th mt hoc nhiu tiu ch, khng c cu tr li no l c.Mi tiu ch nh vy c tnh l mt ME.Khng c ME Tt c cc cu tr li u l khng hoc khng nh gi c.Bc 3: Ly kin chuyn gia v cc bo co nghi ng c ME Cc bo co nghi ng c ME xc nh bng PM c chuyn cho nhm chuyn gia gm 1 chuyn gia v cnh gic dc, 1 chuyn gia v dc l v cnh gicdcv1chuyngiavdclmsngthmnhli.Quytrnhnyca nghin cu c lp vi quy trnh thm nh bo co ADR thng quy ti Trung tm DI&ADRqucgia.Trongtrnghpvicsdngthuccnhgilhp l/thng quy th bo co c quy l khng c ME (Ph lc 8).2.2.2. Mc tiu 2: Nhn din cc sai st lin quan n thuc c mi quan h vi bin c bt li c bo co ThngtinvMEphthincscghichpli(phlc4),sau chuyn cho nhm 2 chuyn gia gm 1 chuyn gia v dc l, cnh gic dc v 1 chuyn gia v dc lm sng km theo bo co gc v bin bn thm nh. Mi lin 27 quan gia ME v AE c nh gi c lp sau trao i cho n khi i n ng thun gia 2 chuyn gia. Nguyntcnhgi:MEccoilcmiquanhtiAEnuvic khng xy ra ME c th d phngmt phn hoc hon ton: 1, vic bnh nhn dng thuc hoc 2,vicxut hinAE trnbnhnhnkhi dngthuc.Nghin cu ny cha xt ti tnh kh thi ca vic d phng ME trong thc t. Thang im nh gi gm ba mc: Khng nh c mi quan h MEAE, C th c mi quan h MEAE v Khng c mi quan h MEAE.2.3.Ch tiu nghin cu tng ng vi mc tiu ra 2.3.1. Ch tiu nghin cu tng ng vi mc tiu 1 S lngv t l boco nghing cMEtrn tngs bo co ca vo nh gi. S lng v t l bo co nghi ng c ME theo loi ME: sai liu dng, bnh nhn t dng thuc k n, li cch dng, tin s d ng vi thuc hoc nhm thuc s dng, ch nh sai, trng lp tr liu, theo di lm sng/cn lm sng khng ph hp, tng tc thuc, sai khong thi gian dng thuc, k n khng ph hp theo c im ca bnh nhn. Thng tin v bnh nhn:oSboconghingcMEphntheogiitnhvtuibnhnhn. Cc lptui tr em cphn loi theo cch phnloi trongPharmacotherapie nh sau: tr s sinh: di 1 thng tui; tr 1 nm: t 1 n 12 thng tui; tr nh: t 1 n6tui;tr ln:t trn6 n12tui; thiunin: t trn12 n 16 tui [76].itngbnhnhnt65tuitrlncphnloilngicaotui [28]. Cnli,itngbnhnhnt17n64tuicphnvo nhmtui ngi ln. oPhn tch s lng cc bo co nghi ng c ME gp theo nhm tui ca bnh nhn; Thng tin v thuc s dng: oS lng v t l bo co nghi ng c ME theo ng dng thuc; 28 oS lng v t l bo co nghi ng c ME theo h dc l. Mt h dc l c xc nh theo phn loi m ATC bc 3 [81]; oCc thuc thng gp ME v cc ME gp phi khi s dng cc thuc .2.3.2. Ch tiu nghin cu tng ng vi mc tiu 2 S bo co nghi ng c mi quan h MEAE; S lng v bo co nghi ng mi quan h vi ME AE theo tng loi ME; Thng tin v AE: oSlngMEtheomcnghimtrngcaAEtrongtngloiME. Trong,mcnghimtrngcphnloitheoquytrnhthmnhca trungtmDI&ADR,tinhnhtheohngdncaWHOdatrncchphn loicaHingh quctvHahpccYucukthutchongkDc phmdngchongi(InternationalConferenceonHarmonisationoftechnical requirementsfor registration ofpharmaceuticalsforhumanuse) ICHE2A.Bo co c xc nh l nghim trng khi ADR c ghi nhn trong bo co dn n t vong; e da tnh mng; buc ngi bnh phi nhp vin iu tr hoc kodithigiannmvincangibnh;lidichngnngnhocvnh vin cho ngi bnh; gy d tt bm sinh thai nhi; hoc bt k ADR c cn b y t nhn nh l gy ra hu qu nghim trng v mt lm sng [32]. oPhn b bo co nghi ng c mi quan h ME AE theo h c quan b nh hng da vo thut ng phn ng c hi theo WHO ART. T chc c th bnhhngcphnloitheomPhnnhmhcquanbc1(System Organ Class 1 SOC1) [59]; oPhnbbocotheonixyraphnng(tinhhaycsytCSYT); Loi ME v s dng khng sinh nghi ng c mi quan h vi AE.2.4.Phng php x l s liu D liu c nhp vo v qun l bng phn mm Microsoft Access 2010 sau c x l bng phn mm Microsoft Access 2010 v Microsoft Excel 2010. 29 Nghin cu s dng cc hm SUMIF, COUNTIF, COUNT trong Microsoft Excelmtccbinnhn3gitrnhvicbococ/nghing/khngc ME, c/nghi ng/ khng c mi quan h ME-AE, gii tnh bnh nhn, a im xy ra phn ng v mc nghim trng ca ME. Nghin cu s dng lnh lc, pivot table trong Microsoft Access v Microsoft Excel m t cc bin c nhiu gi tr hn nh h dc l ca thuc, hot cht, nhm tui bnh nhn, loi sai st v loi sai sttheonhm tui.Phntch cc h dc l vcchot cht hay gpnht s dng chc nng lc cc gi tr ln nht ca pivot table. D liu trng lp trong qu trnh x l c loi bng lnh Remove dublicates. 30 CHNG 3. KT QU pdngquytrnhnhgiboco nh trnhby trn, thu c kt qu nh sau: Hnh 3.1. S lng bo co a vo nh gi v phn tchtheo quy trnh nghin cu Bo co khng c ME (n = 12) Bo co nghi ng c mi quan h ME-AE c a vo phn tch (n = 85) BC khng nh c mi quan h ME-AE (n = 60) BC c th c mi quan hME-AE (n = 25) Bo co nghi ng c ME c a vo phn tch (n = 152) Bo co khng c mi quan h ME-AE: n = 67 BC khng nh c ME (n = 127) BC c th c ME (n = 25) Chuyn gia nh gi tnh hp l cavic s dng thuc Phng php P Bo co nhn c t 16/12/2013-15/02/2014 (n = 1013) Tng bo co loi: n = 250 Test phn ng: n = 118 Khng r hot cht: n = 18 Khng r phn ng: n = 15 Khng r l do s dng: n = 56 Mi lin quan thuc-phn ng khng chc chn: n = 29 Khng c ti liu i chiu: n = 16 Bo co c a vo nh gi(n = 763) Bo co pht hin ME theo phng php P (n = 64) Bo co khng c ME (n = 599) Loi bo co Chuyn gia nh gi mi quan hME-AE 31 3.1.Nhn din cc sai st lin quan n thuc 3.1.1. S lng bo co nghi ng c sai st lin quan n thuc Xutphtt1013boconhnctronggiaion16/12/2013 15/2/2014, 763 bo co c a vo nh gi sau khi loi bo co theo tiu chun loi tr. S dng PM, 164/763 bo co c pht hin c ME. Sau khi tham kho kin chuyn gia, 12 trong s 164 bo co ny c cho l khng c ME (ph lc 5) cn 152 bo co c nh gi l nghi ng c ME (gm 127 bo co khng nh c MEv25boconghingcME),chim20%sbococnhgi(xem hnh 3.1).3.1.2. Loi sai st ghi nhn c trong cc bo co nghi ng c sai st lin quan n thuc Tng s 152 bo co nghi ng c ME lin quan n 218 lt ME bo co c ghi nhn theo 11 loi sai st c trnh by trong hnh 3.2. Trng hp nhiu hn hoc bng hai thuc trong mt bo co cng mc mt loi ME s c tnh l 1 lt ME bo co. Trong , 36/152 bo co c ME lin quan n bnh nhn (Pa) viloiMEbnhnhntdngthuckn.CcMElinquannthchnh ngh nghip (Pr) pht hin c trn 140/152 bo co vi cc loi ME v liu dng, cchdng,chnh,tinsdng,trnglptrliu,theodilmsng/cnlm sngkhngphhp,knkhngphhptheocimcabnhnhnvsai khong thi gian dng thuc. Nhnxt:CcMEthnggpnhtlsaistvliudng(65boco, chim 42,8% cc bo co nghi ng c ME), trong c 38/65 (58,4%) bo co c liu dng cao hn liu khuyn co. Tip theo l cc sai st v ch nh (45 bo co, chim29,6%),bnhnhntdngthuckn(36boco,chim23,7%),cch dng(28boco,chim18,4%).Sdngthuctrnbnhnhnctinsdng thuc hoc nhm thuc (16 bo co, 10,5%) v tng tc thuc (13 bo co, 8,6%) cng chim t l ng k. Cc tng tc u xp loi l c th do khng phi l tngtcchngchnhv thngltngtcdcnghc.Cghinhncc trnghptheodicnlmsng/lmsngkhngphhp,sdngthuckhng 32 ph hpvi c imbnh nhn (tui),sai khongthi giandngv ngdng thuc. Do c th ca CSDL nghin cu, cc sai st v sn phm (cht lng thuc thp,thucgi),saistdobnhnhnkhngtunthvccsaistdothchnh ngh nghip khc hu nh khng ghi nhn c trong mu nghin cu. 3.1.3.Thng tin v bnh nhn a, Thng tin chung v tui v gii tnh ca bnh nhn Thng tin lin quan n tui v gii tnh ca bnh nhn c trnh by tm tt trong bng 3.1. Nhn xt:Hnh 3.2: S bo co nghi ng l ME theo loi sai st ghi nhn c (n=152) 33 oT l bnh nhn n (52,6%) trong cc bo co nghi ng c ME cao hn bnh nhn nam, tuy nhin khng c s khc bit v t l nam/n gia hai nhm.oCc bo co nghi ng c ME phn b rng khp trn cc i tng bnh nhn t 5 ngy tui n 84 tui. T l bo co nghi ng vi ME theo nhm tui cng ng bin vi t l bo co c nh gi theo mi nhm, tuy nhin nhm tr em di 2tui c t l bo co nghi ng c ME cao hn t l trong tng s bococnhgi(18,4%sovi13,5%).Nhnchung,bocotptrung ngi ln (95 bo co; 62,5%), nhng vn c mt s lng ng k cc bo co v i tngbnhnhnltr s sinh, tr 1tui v tr nh(di 2tui, 28 bo co;18,4%),trem(tngcng36boco;23,7%)vngicaotui(21bo co; 13,8%).Bng 3.1. Tui v gii tnh ca bnh nhn trong cc bo co c nh gi v bo co nghi ng c lin quan n ME c im bnh nhn Cc bo co c nh gi (n=763) Cc bo co nghi ng c ME (n=152) Gii tnh N398 (52,2%)80 (52,6%) Nam365 (47,8%)72 (47,4%) Khng c thng tin2 (0,6%) tui S sinh (< 1 thng tui)5 (0,7%)1 (0,7%) Tr 1 nm (> 1 thng 1 tui)50 (6,6%)13 (8,6%) Tr nh (> 1 tui 2 tui)48 (6,3%)14 (9,2%) Tr ln (> 2 tui 12 tui)16 (2,1%)5 (3,3%) Thiu nin (> 12 tui 16 tui)14 (1,8%)3 (2,0%) Ngi ln (16 tui59 tui)527 (69,1%)95 (62,5%) Ngi cao tui (t 65 tui)103 (13,5%)21(13,8%) 34 b, Loi sai st ghi nhn c theo nhm tui Bng di y trnh by s bo co nghi ng c ME theo tng loi sai st trongminhmtui.Mibococthcnhiuhnmtloisaistvkhi bo co c tnh cho tt c cc loi sai st pht hin c. Bng 3.2. S lngbo co c tng loi ME theo nhm tui Loi sai st 0-16 tui 17-64 tui 65-84 tui Liu dng 193610 Ch nh 9333 T dng thuc k n 8271 Cch dng 9163 Tin s d ng vi thuc hoc nhm thuc s dng 115 Tng tc 355 Trng lp iu tr 7 Theo di lm sng/ cn lm sng khng ph hp 22 K n khng ph hp theo c im ca bnh nhn 11 Khong thi gian dng thuc 1 ng dng thuc 1 Tng s bo con = 36n = 95n = 21 Nhnxt:SailiudnglMEthnggpnhtc3nhmtui:chim 19/36 boco tngngvi52,8% i tngtr em; 36/95 boco tngng vi 37,9% i tng 1764 tui; 10/21 bo co tng ng vi 47,6% i tng ngicaotui.Tuynhinngicaotuivtrem,slngbocosailiu dng chim t l cao vt tri so vi cc ME khc. 35 oNgoi sai liu dng, cc loi ME ng ch trn i tng tr em l cc MEvchnh(9/33boco),cchdng(9/33boco)vtdngthuck n (8/33 bo co); trong khi ngi gi li l vn tng tc thuc (5/21 bo co) v li cch dng (3/21 bo co). ivinhmbnhnhn1764tui,cc MEthnggpnht sau liudngl ch nh (33/95boco) v bnhnhnt dngthuckn(27/95boco).CcMEvlicchdng,tinsdng cng xut hin vi t l ng k.3.1.4. Thng tin v thuc nghi ng c ME a. ng dng ca thuc nghi ng trong cc bo co nghi ng c ME Tngcng186ltthucnghingcMEcghinhntrong152bo co.MibococthcccthucnghingcMEtheonhiuhn1ng dng,khibococtnhchottcccngdngcathucnghingc ME.Tlsbocotheotngngdngtrntngsbococtrnhby trong bng di y. Bng 3.3. S bo co nghi ng c ME theo ng dng thuc ng dngS bo co (n=152)T l (%) Ung9059,2 Tim, truyn tnh mch5234,2 Tim bp138,6 t trc trng32,0 Ngm10,7 Khng r21,4 Nhn xt: ng dng ph bin nht ca thuc nghi ng l ng ung (90 boco,59,2%),tnhmch(52boco,34,2%),timbp(13boco,8,6%). Ngoira,cngghinhnmtsboconghingcMEvithuccsdng vi ng dng ti ch.36 b. Phn loi theo h dc l ca cc thuc nghi ng c ME Tngcng152boconghinglMEclinquann186ltthuc nghi ng c ME. Thng tin v cc h dc l hay gp ME trong s dng c m t trong bng 3.4.Bng 3.4. Cc nhm dc l hay gp sai st trong s dng STT M ATC Nhm thuc S bo co % Tng s bo co nghi ng c ME (n=152) 1J01D Khngsinhnhmbeta-lactam khc (*) 3925,7 2J01CCckhngsinhnhm beta-lactam, penicillin1811,8 3J04ACc thuc iu tr lao1610,5 4J01FCcmacrolid,lincosamid v streptogramin 138,6 5J01GCc aminoglycosid127,9 6M01AThucchngvimv chngthpkhp,khng steroid 117,2 7N02BCc thuc gim au v h st khc (**) 74,6 8J01XCc khng sinh khc74,6 9J01MCc quinolon63,9 10J01ECc khng sinh sulfonamid v trimethoprim 63,9 Chthch:(*)Khngsinhnhmbeta-lactamkhcbaogmcc cephalosporin, monobactam v carbapenem. (**)Ccthucgimauvhstkhcbaogmacidsalycilicvdn cht, cc anilid. Nhn xt: ME ghi nhn c hu ht cc nhm thuc, phn b ch yu nhm khng sinh (119 bo co, chim 78,3% tng s bo co). Trong nhm khng 37 sinhthcckhngsinhbeta-lactamchim tlln(nhmJ01Dcckhngsinh beta-lactam khc: 39 bo co, 25,7% tng s bo co nghi ng c ME; nhm J01C cc khng sinh beta-lactam, penicillin: 18 bo co, 11,8%). S lng ME v nhm thuciutrlao(16boco,10,5%);nhmmacrolid,lincosamid,streptogamin (13boco,8,6%);ccaminoglycosid(12boco,7,9%)cngchimtlkh cao. Ngoi ra cn cc thuc thuc nhm NSAIDs (11 bo co. 7,2%) v cc thuc gim au v h st khc (7 bo co, 4,6%, ch yu l paracetamol). c.Ccthuccghinhnnhiunhttrongccboconghingc sai st lin quan n thuc v loi sai st tng ng Bng 3.5 trnh by 20 hot cht ghi nhn c nhiu bo co nghi ng c ME nht v loi sai st tng ng i vi tng hot cht. Bng 3.5. Cc thuc thng gp sai st khi s dng STTHot chtS ME(a) Loi ME(b) LiuCCDTTDRxTGTLD 1Amoxicillin(c)13284151 2Rifampicin (c)13941 3Cefotaxim105611 4Isoniazid (c)88 5Cefuroxim61141 6Paracetamol643 7Ceftriaxon644 8Streptomycin651 9Pyrazinamid (c)5611 10Ciprofloxacin5411 38 STTHot chtS ME(a) Loi ME(b) LiuCCDTTDRxTGTLD 11Metronidazol (c)52112 12Vancomycin54132 13Ceftazidim423 14Cefalexin412123 15Cloramphenicol4414 16Penicillin V43112 17Cotrimoxazol421221 18Diclofenac41122 19Spiramycin4313 20Cefixim31201 Ch thch:(a) S ME: S bo co nghi ng c sai st lin quan n thuc. (b) Liu:sailiudng;C:saichnh;CD:saicchdng;TT: tngtc;D:tinsdngvithuc,nhmthuc;Rx:bnhnhnt dng thuc k n; TG: sai khong thi gian dng thuc; TL: trng lp tr liu; D sai ng dng thuc (c) Bao gm c thuc dng phi hp c cha hot cht , c th: Amoxicilin: amoxicilin/amoxicilin+clavulanat;Rifampicin: R/RH/RHZ, pyrazinamid: Z/RHZ, isoniazid: H/RH/RHZ;Metronidazol: metronidazol/metronidazol+spiramycin;Spiramycin: spiramycin/metronidazol+spiramycin. 39 Nhnxt:TrongsccthucthngghinhncME nhttrongmu nghin cu, 18/20 l cc khng sinh, hai thuc cn li l diclofenac v paracetamol. Cc ME khi s dng cc thuc ny thng l v liu dng, cch dng, ch nh v t dng thuc k n.oCc thuc hay gp ME v liu nht l cc thuc chng lao (R, H, Z hoc dngkthpvi17bocovstreptomycinvi5boco).MEvchnh thnggpamoxicilinvi8boco,chyulsdngtrongtrnghp khng c/khng r nguy c nhim khun. Li cch dng ch yu thuc v khng sinh h penicillin, cefotaxim vi 6 bo co, amoxicilin vi 4 bo co, cefuroxim vi4boco,ceftriaxonvi4boco,thngdodngsaislntrongngy. Ccthucknhaycbnhnhntdnglamoxicilinvi5boco, thngtrongcctrnghpccbnhthngthngnhst,ho,auhng;v cloramphenicolvi4boco,ucdngnhmmcchiutrrilon tiu ha. 3.2. Nhn din cc sai st lin quan n thuc c lin quan n bin c bt li c bo co3.2.1. S lng bo co c mi quan h gia sai st lin quan n thuc v bin c bt li Trong152bo co nghi ngc ME, 85 boco nghi ngcmiquanh gia 131 ME v AE, trong 60 bo co(7,7 % tng s bo co nh gi)khng nh c mi quan h MEAE, 25 bo co (3,3 %) c th c mi quan h ME AE (Ph lc 6). Nh vy s bo co nghi ng c mi quan h ME AE chim 85/763 s bo co c nh gi, tng ng 11,1%. 3.2.2. Phn tch cc sai st lin quan n thuc nghi ng dn n bin c bt li theo loi sai st Tng s 85 bo co nghi ng c mi quan h ME AE lin quan n 132 ME (Ph lc 5). S cc ME nghi ng c lin quan n AE c bo co c biu din trong hnh 3.3. 40 Nhn xt: Cc ME c nh gi l c th l nguyn nhn gy ra AE c bo co c mt phn ln l ME v ch nh (n = 38; 44,7%) v bnh nhn t dng thuc k n (n = 36;42,4%). MEvliudnggyAEchimt lnh hn (n = 18;21,2%)mcdghinhncvitllnkhinhgi boconghingc ME. C 18 trng hp u dng liu cao hn liu khuyn co, mt phn l khng hiu chnh liu ph hp theo i tng tr em v ngi cao tui. Ngoi ra cc loi ME nh s dng thuc trn c a bnh nhn c tin s d ng (n = 15 ; 17,6%); li cch dng (n = 10; 11,8%) cng chim t l ng k. Hnh 3.3. S bo co nghi ng c mi quan h gia ME v AE theo loi ME (n=85) oHai trng hp tng tc thuc nghi ng gy AE c bo co l tng tc metronidazol ru nghi ng gy ra triu chng kh th, run git tay chn, 41 tng nhp tim trn bnh nhn; tng tc haloperidol olanzapin nghi ng gy run c (c th l hi chng gi parkinson) trn bnh nhn. oHaitrnghptrnglptrliunghing gyAEulbnhnhns dngcnglc2NSAIDs.Trnghpthnhtbnhnhndngkthp Cadicelox(celecoxib)200mgvMebilax(meloxicam)7,5mg,xuthinphv nga. Trnghp th2,bnh nhn dngkthp Nimis(nimesulide)v Ibucet (ibuprofen + paracetamol), xut hin lot ng tiu ha.oTrng hp nghi ng ME v ng dng gy AE l khi tim tnh mch chmceftriaxontrnbnhnhiviliucao(2000mg/14kg/ngy,gpiliu khuynco),gyphnngrtrun,hthong,mchnhanh.Chuyngiathm nhnhnxtcthdngliucaoceftriaxontiICUnhngphitruyntnh mch,bnhnhntimtnhmchchmliucaocthgyphnngtngt phn v. 3.2.3.Thng tin v AE nghi ng lin quan n ME a. Mc nghim trng ca phn ng trong cc bo co nghi ng c mi quan h sai st lin quan n thuc v bin c bt li Trong85bococnhgilcmiquanhMEAE,52boco cnhgimcnghimtrngtheoquytrnhcaTrungtmDI&ADRl nghimtrng,chim61,2%.Tlnycaohnhntlboconghimtrng trongccboconghingcME(47,7%)vtrongccbococnhgi (56,2%).S bo co nghi ng c mi quan h ME AE theo loi ME v mc AE c th hin trong hnh 3.4. Nhnxt:100%boconghingcmiquanhgiavictheodilm sng/cnlmsngkhngphhp,saingdngthucvtrnglptrliuvi AEcbocoulvccAEnghimtrng.CcMEctlgyraAE nghimtrngcphthincaoltinsdng(13/15;87%)vbnhnhnt dng thuc k n (29/35 bo co; 83%). Cc ME nghi ng gy AE trong t l 42 AE nghim trng thp hn gm c ch nh (20/38 bo co; 52,6%), tng tc (1/2 bo co; 50%), liu (8/18 bo co; 44%) v cch dng thuc (2/10 bo co; 20%). Hnh 3.4. Mc nghim trng ca AE c bo co theo loi ME (n=85) b. Bin c (AE) ghi nhn c trong cc bo co c mi quan h ME AE theo h c quan b nh hng Cc AE nghi nglhuqu ca MEphnloi theo t chc c thb nh hng c trnh by trong bng 3.6. Trong cng mt bo co c th c nhiu AE v phn loi theo t chc c thca chng c th khc nhau, khi bo co c tnh cho tt c cc phn loi t chc c th ca AE ghi nhn c. Nhn xt: AE c ghi nhn nhiu nht l cc ri lon trn da v m di da (n=57, 61,2%). Cc ri lon h tiu ha gp 16 bo co (18,8%), bng vi s bo co c ri lon v tm thn. Ri lon ton thn gp 13 bo co (15,3%). Ri lon thn kinh trungng v ngoi bin cng chim t l ng k vi 12 bo co, 14,1%. Cc h c quan khc nh h sinh dc, h tim mch, h tit niu, h gan mt, 43 rilontivtrdngthuc,rilonthgic,rilontrntremvtrnh,ri lon bt thng cng c ghi nhn. Bng 3.6 T l bo co nghi ng c mi quan h ME AE theo t chc c th b nh hng Phn loi v tr phn ngS bo co (n=85)T l (%) Ri lon da v m di da5767,1 Ri lon h tiu ha1618,8 Ri lon tm thn1618,8 Ri lon ton thn1315,3 Ri lon thn kinh trung ng v ngoi bin1214,1 Ri lon h sinh dc n44,7 Ri lon h gan mt33,5 Ri lon d thng (Secondary terms events)22,4 Ri lon ti v tr dng thuc11,2 Ri lon trn tr em v tr nh22,4 Ri lon th gic11,2 c. Thng tin v ni xy ra AE Trongtngs85boconghingcmiquanhMEAE,41boco (48,2%)c thngtincho thyphnngxuthinngoi cngng (bnh nhns dng thuc xut hin phn ng ri mi vo CSYT iu tr phn ng), 29 bo co cthngtinchothyphnngxuthintiCSYT(34,1%),sbococnli (17,7%) khng c c s nh gi ni xy ra phn ng.Tngs36/85(42,4%)boconghingcmiquanhMEAE,thuc nghingcMEgyAEcbnhnhnt s dngkhngtheon(thucOTC hoc thuc k n).44 3.2.4. Thng tin v thuc lin quan n sai st c th dn n bin c bt li c miu t a,Phnbbo conghingcmiquanhgiasai stlinquannthucv bin c bt li theo nhm dc l 85 bo co nghi ng c mi quan h gia ME v AE c bo co c lin quan n 93 lt thuc nghi ng c ME gy AE. Trong , nhm thuc khng sinh chim u th vi 64/85 bo co, 75,3%. T l cc bo co theo h dc l hay gp nht c miu t trong bng 3.7.Bng 3.7. Phn b bo co nghi ng c mi quan h ME AEtheo cc h dc l hay gp nht STTM ATCH dc lS bo co (n=85) T l (%) 1J01DKhng sinh nhm betalactam khc(a)2124,7 2J01CKhng sinh nhm betalactam, cc penicillin 1214,1 3J01FCc macrolid, lincosamid v streptogramin89,4 4M01AThucchngvimvchngthpkhp,khng steroid 89,4 5J01ESulfonamid v trimethoprim67,1 6J01GCc aminoglycosid67,1 7J04ACc thuc iu tr lao44,7 8J01BCc amphenicol44,7 9J01XCc khng sinh khc44,7 10N02BCc thuc gim au v h st khc(b)33,5 Chthch:(a)Khngsinhnhmbetalactamkhcbaogmcc cephalosporin, monobactam v carbapenem.45 (b)Ccthucgimauvhstkhcbaogmacidsalycilicv dn cht, cc anilid. Nhnxt:TrongccMEnghinggyraAEvthucthucnhmkhng sinh, ni bt nht vn l cc khng sinh beta-lactam khc ngoi penicillin (bao gm cc cephalosporin, monobactam v carbapenem) vi 21 bo co, chim 24,7%; cc macrolid,lincosamidvstreptograminvi12boco,chim14,1%vcc penicillinvi8boco,chim9,4%.TheosaulccNSAIDsvin=8,chim 9,4% v cc thuc h st gim au khc (n = 3; chim 3,5%). Cc h dc l cn li chim t l rt thp. 46 b, Sai st trong s dng khng sinh nghi ng dn n bin c bt li S lng bo co c cc loi ME v s dng khng sinh nghi ng dn n AE c tm tt trong hnh 3.5. Hnh 3.5. S bo co nghi ng c mi quan h ME v khng sinhAE (n=64) Nhnxt:TrongccMEvsdngkhngsinh,tdngthucknl nguyn nhn hng u dn n AE c bo co (n = 31, 48,4%). Sai ch nh (n = 30,46,9%),sailiudng(n=14,21,9%),tinsdng(n=10,15,6%),licch dng (n = 8, 12,5%) cng l nhng nguyn nhn ng lu . Cc trng hp tng tc thuc, trng lp tr liu v sai ng dng thuc c m t pha trn.47 CHNG 4. BN LUN Pht hin v d phng s xut hin AE trn ngi bnh lun l mt trong nhng mc tiu quan trng nht ca CGD v m bo an ton thuc. Nhiu nghin cu ch ra rng mt t l ln cc AE/ADR l phng trnh c do chng l hu qu ca cc ME [27], [37]. Bn cnh cch tip cn pht hin ME thng qua quan st thc hnh lm sng ti cc CSYT, bo co t nguyn v AE/ADR ca cc trung tm CGDngycngccoilmtngundliuphongphvtimnngpht hin cc ME v cc AE/ADR c kh nng phng trnh c [61]. Nghin cu ny c thc hin nhm bc u nh gi tim nng ny ca CSDL bo co ADR ti Vit Nam.4.1.Bn lun v phng php nghin cu Vic s dng CSDL bo co t nguyn pht hin ME c mt s u im nh sau: Vicnhgilhicunnthigianthchintngingn,chiph thp hn so vi cc cch tip cn khc. CSDLkhln,mucchncthntrtnhiubnhvin/khoa phng trn hu khp c nc. KhngyucungibocophinhnthcclmtME;trnh cmtssaiskhithchinnghincuquansttrctipnhtmlengi ME ca cn b y t khi c mt ngi nghin cu.Nghin cu s dng b tiu ch ca phng php P (PM), mt phng php mi c pht trin bi nhm chuyngia ca WHO v c cch phn loi ME kh chi tit. Phng php ny da trn cch xc nh cc yu t nguy c c th phng trnh c lm tng kh nng xy ra ADR, do gip nh hng chi tit v ME v mt h thng v bin php c th dng khc phc ngun ME. Tuy nhin, do cch tip cn t AE c bo co v kh nng phng trnh AE , PM b qua cc ME khng trc tip gy ra AE c bo co (xp loi tiu ch l khng p dng c). 48 PM c k vng l phng php c th cho CSDL CGD v s gip ch cho vic so snh t l vi cc nghin cu t cc trung tm CGD khc trn th gii.Trongnghincuny,cclachntrlichomitiuchcthay i so vi nguyn bn ca PM t c/ khng/ khng r/ khng p dng c thnh c/c th/khng/khng p dng c cho ph hp hn vi c th CSDL bo co VitNam.NusdngnguynbncaPM,huhtccbocoADRtrong CSDLnghincusctnhtmttiuchkhngnhgic(v dnhd ng penicillin khi bo co khng c thng tin v tin s), v bo co b xp loi l khngnhgic.Mtkhc,vicathmlachncthgipngi nghin cu thun tin hn khi c nhiu bng chng cho rng vic s dng thuc c ME nhng cha thc s c th khng nh t cc thng tin trn bo co ADR. Theo mt nghin cu tng quan v cc phng php xc nh AE phng trnh c, cch lm ny gip hn ch c sai st s xy ra khi thang im nh gi c t la chn hn so vi kh nng phn tch ca ngi nghin cu [29]. Tiu ch s 12 cng c thay i t tng tc thuc-thuc thnh tng tc thuc ni chung ghi nhn c cc sai st mt cch ton din hn. Nhiu nghin cu khng ch r ngun CSDL thng tin thuc dng nh gi xc nh ME [20], [38], trong khi mt s nghin cu s dng SmPC nh gi pht hin ME t CSDL bo co t nguyn [34] [55]. Phng php P cng khuyn khch s dng SmPC hoc cc hngdn iu tr quc gia, quc t c cp nht nh gi cc tiu ch [62]. Cch lm ny c bit thun tin nhiu quc gia trn thgiichthngCSDLSmPCcphduyttrctuynkhhonchnhv thng nht.TiVitNam,chacmththngSmPCcphduytddngtruy cp c th c dng lm ti liu tham kho chnh thc. T hng dn s dng thuc km theo sn phm cha tht s phn bit gia SmPC, thng tin cho cn b y t vi thng tin cho bnh nhn (Patient Information Leaflet PIL). Cc CSDL thng tin thuc bng ting Vit c th k n l Dc th Quc gia Vit Nam 2009 [3], Mims (Mims Hngdn s dngthuchoc MimsOnline [68])v Vidal Vit 49 Nam [7]. Mt nghin cu t nm 2010 cho thy kh nng cung cp thng tin cng nh tnh thng nht ca cc ti liu ny cn hn ch, trong xp theo th t t cao nthplDcthQucgiaVitNam2009,VidalVitNamvMims Hng dn s dng thuc [1]. Tuy nhin, nu xt v tnh cp nht cng nh thng tin chi tit c trng cho tng bit dc, dng bo ch v thnh phn hm lng ng vai tr nh mt SmPC th Vidal Vit Nam v Mims li c u th hn. ng trn quan im kh nng tip cn ca cn b nhn vin y t, cng nh tnh cp nht cangunthngtin,nghincunyutinsdngtiliuthamchiulcc CSDLthngtinthucbngtingVitbaogmVidal20142015[68]/Mims Online Vit Nam(chuynlunvbitdc)[7]vDcthQucgiaVit Nam [3] (chuyn lun v hot cht). Mtkhc,cngngtrnquanimkhnngtipcncacnbnhn vin y t ti thi im xy ra bin c, nghin cu s dng Danh mc thuc khng knbanhnhkmtheothngts08/2009/TTBYTthayvdanhmccp nht hn banhnhkm theo thngt s 23/2014/TT-BYTvothng 6nm 2014. Danhmc nm2014 c s iu chnhgim bts thuck n,tuy nhinxt trongmunghincuthkhngcskhcbitnupdngmttronghaidanh mc ny. Bn Dc th Quc gia Vit Nam nm 2009 c chn v nhm nghin cu xt thy bn nm 2012 cha c chuyn lun cp nht cho tt c cc hot cht v cha c ph bin rng ri. Cc ti liu ny c th s hu ch trong cc nghin cu v sau. Hn ch ca phng php nghin cu Hngtipcncanghincucngcnhnghnchcavicsdng CSDL bo co ADR t nguyn nh: hin tng bo co t hn thc t [41], khng chophpctnhtnsutxyrabinc.BnthnthitkbocoADRthiu nhiuthngtinxcnhMEnhthngtinvtctruynthuctimtnh mch, thng tin v tnh trng lm sng ca bnh nhn, thng tin v hn dng, cht lng thuc, thuc gi. Mt khc cch tip cn hi cu ph thuc rt nhiu vo cht lng bo co v khng cho php thu thp thm thng tin cn thit. 50 Cctiliuthamchiucchntrongnghincucachngticn nhiu hn ch nh: cha thng nht, cha y , cha cpnht [1] v c th nh hng n kt qu nghin cu. Vic c thm bc nh gi r sot li cc ME xc nh c t PM khi so snh vi ti liu i chiu loi b nhng trng hp vic sdngthuclhpl/thngquygipphnnohnchnhcimny.Tuy nhin, vic cha c bc s iu tr trong nhm chuyn gia thm nh c th l mt hn ch do thc hnh thuc ghi nhn trong bo co cha c xem xt di nhiu quan im. MtsnhnghincunhgiPMltnnhiucngscvthigian [38], [62], do c th s gy kh khn nu p dng trong thc hnh thng quy. 4.2.Bn lun v kt qu nghin cu 4.2.1. Kt qu v sai st trong s dng thuc TlboconghingcMEl19,9%tngsbococnhgi. Trn thc t, c nhiu nghin cu theo di pht hin ME trc tip t CSYT nhng chcmtstccnghincutrnCSDLbocotnguyn.TiVitNam, nghin cu quan st, tin cu ca Dng Th Thanh Tm v s dng thuc cho tr em mt c s y t cho thy 68,6% liu sai st c ghi nhn trn tng s 995 liu thuc c nh gi [9]. Mt nghin cu khc ca Nguyn Hng Tho v cng s v sai st trong khu chun b v s dng thuc cho thy khong 37,7% lt thuc s dng c xy ra ME [46].RtkharamttlchungvMEvsosnhtlMEgiacc nghin cu khc nhau do s khc bit ln v phng php nghin cu v i tng nghin cu, cht lng h thng y t, cht lng thng tin trn CSDL, kh nng thu thp thng tin b sung nh gi. T l bo co c ME (19,9%) trong nghin cu nykh tng ngvinghin cuca trnCSDL CGD Malta(Tanti, 2012) l 17,9%(56/319),cthdomctngngcaogiabtiuchxcnhME bng PM vi cc loi sai st xc nh c trong nghin cu ca Tanti [55].Cc loi ME thng gp trong nghin cu ny kh tng ng vi nghin cu ca Tanti: ln lt l sai v ch nh, theo di, ME do bnh nhn (ch bao gm 51 cc ME v tun th, nhm ln) v ME do khu cp pht (trong bao gm ME do cung cp thuc k n cho bnh nhn khng c ch nh ca bc s) [55]. T l ME v theo di iu tr t hn nghin cu ny c th l do CSDL c qu t thng tin nh gi. Cc ME thng gp tng t cng gp nghin cu ca Kumac New Zealand:saivliuvtheodibnhnhn(baogmMEvtngtc,tinsd ngthucvtheodilmsng/cnlmsngkhngphhp)[38].LoiMEc nghi ng gy ra AE thng gp nht l sai v ch nh (44,7%), tng t vi d liu nhn c t mt nghin cu v pAE t CSDL Thy in (56%) [42].ng lu , t l bnh nhn t dng thuc k n chim t l cao (36/152, 23,7%) so vi nghin cu ca Tanti (5/56, 8,9%) [55]. Cc ME v t thuc k n khngcnhcntrongnghincucaNewZealand,tuynhinphnloi dng sai thuc ch chim 1/61 trng hp ME [38].Do cc c th ring v dc ng hc, nguy c cao xy ra sai st v phn ng bt li, cng nh do thng b loi tr khi la chn i tng nghin cu cho thnghimlmsng,tremvngicaotuilnhngqunthbnhnhnc nguyccaoccbitquantmtrongcngtcCGDtrnthgii[44],[28], [76]. T l bo co pht hin ME trn bnh nhi trong nghin cu ca chng ti kh cao (23,7%) so vi t l trong nghin cu ca Tanti (nhm tui t 0-19 tui chim 7/96 bo co, tng ng 7,3%). Trong khi phn ln ME xc nh c trong nghin cucachngtithuclatuingiln(1764tui)v cnchimtlthp trn i tng ngi cao tui, th cc bo co trong nghin cu ca Tanti v Kumac li ch yu phn b i tng trn 50 tui [38], [55]. Tt c nhng im khc bit ny c th c gii thch mt phn thng qua so snh t l bo co ADR theo cc nhm tui trong mu nghin cu vi t l bo co ADR trong CSDL ca cc nc pht trin. Trong khi s lng bo co ADR trn ngi cao tui chim t l kh cao cc nc pht trin, mt phn do s tp trung vo i tng ny trong chnh sch cnhgicdc[44],tlbocoADRtrnngicaotuicnkhthptrong CSDL CGD Vit Nam. 52 Tuy nhin, nhng d liu hn ch v ME trn i tng ngi cao tui vn cho thy hnh nh s b v cc ME thng gp la tui ny. Sai st v liu l vn chnh yu, do nhng thay i v dc ng hc v p ng vi thuc, theo sau l cc tng tc thuc, do c im ca i tng ngi cao tui l a bnh l, thngphisdngkthpnhiuthuc.Ktqunytrngviphntchtrong nghin cu ca Kunac [38]. im khc bit l trong nghin cu ca chng ti cng ghinhncmttlngkccsaistvchnhvcchdngthuctrn ngi cao tui. V cc loi ME xy ra trn bnh nhi, nghin cu cho thy mt t l vt tri ccMEvliudng,ctrngchosphctpcachliuthuctrem. CchdngcnglMEngghinhn.ycngl2loiMEthnggpnht trong mt nghin cu khc v i tng bnh nhi trn CSDL Hn Quc [64]. SosnhvnhmthuchayxyraME,nghincu chothynhmkhng sinhngutrongdanhschccthucgyME,gingnhmtsnghincu khc trn th gii [38]. Tuy nhin t l ME khng sinh mc cao (70%) trong khi ccnghincukhcctlccnhmthuckhngsinh,thuctcdngtrnh thn kinh, thuc tc dng trn tim mch tng i cn bng [34], [38], [42]. Kt qu ny tng ng vi mt t l cao ME v bnh nhn t s dng thuc k n (m a phnlkhngsinh)cthnghincuny,mcdcthcmtphnnh hng v s khc bit v nhn khu hc v m hnh bnh tt ca tng nc. Lu rngitngbnhnhncaccnghincukhcthngctuicaohnc thnhhngnloithucthngcsdng[38],[55].Tuynhin,thct ny cng t ra vn cn mt chin lc qun l s dng khng sinh cht ch hn. Theo nghin cunm1998 caNguyn ThKim Chc, khngsinhchim khong 17% s thuc c bnkhngk n v 90% trongs l khngsinh ph rng [47]. Mtnghincumihnnm2014vnchothytlbnthuckhngsinh khng theo n l 8890% nh thuc khng t tiu chun Thc hnh nh thuc tt(GoodPharmacyPracticeGPP)cngnhnhthucttiuchunny. Amoxicillin l khng sinh c bn nhiu nht (13%), gii thch cho t l xut hin 53 saisttrongsdngthucnycaotrongnghincucachngti.Nghincu cngchrarngldomuakhngsinhphbinnhtnngthnlho(32%), thnh th l st (22%). y cng l cc sai st v ch nh ca khng sinh hay gp trong nghin cu ca chng ti [23]. Nh vymc d ch tip cnmt cch gin tip qua bo co ADR, nhng ME pht hin c trong nghin cu ca chng ti phn no phn nh c tnh hnh s dng thuc trn thc t. 4.2.2. Kt qu v sai st trong s dng thuc nghi ng c mi lin quan vi bin c bt li c bo co Boco cmi quanh ME AE chim 11,1%(85/763)tngsboco c nh gi. Mc d nghin cu khng i su vo nh gi kh nng phng trnh c ca AE nhng nu coi y l nhng bo co v AE c kh nng phng trnh cthtlnytngngvimtsnghincukhctrnthgiivpAE (14%17%)[34],[42].Tngtnhtrn,skhcbitvtlnycngcth c gii thch bi s khc bit v CSDL v phng php nghin cu.Dottccctrnghpbnhnhntdngthucknucphn loi l ME nghi ng gy ra AE, t l ny nhm cc bo co nghi ng c mi quan hMEAEcaovttri(41,2%),cbitltrongsdngnhmthuckhng sinh. S khc bit ny c th n t h thng qun l phn phi thuc k n Vit Nam cn nhiu lng lo so vi cc nc pht trin. Mt nghin cu t nm 1998 2 nh thuc nc ta cho thy di 1% bnh nhn mua thuc c n ca bc s v 94,9%tquytnhlachnthucmua[47].Mtkhc,NewZealand,quy trnhqunlthuckncthchinrtnghimngt.Midcphmc chialmbnphnnhm:thucknchcbnvincabcs;thuc dc s ch c bn sau khi tham kho kin dc s; thuc nh thuc ch c bn nh thuc hoc mt s quy thuc nng thn v thuc OTC (over-the-counter) l thuc c bn cc quy bn l nh siu th hoc trm xng [79]. Kt qu nghin cu ch ra rng, nhiu trng hp ME v liu c pht hin nhng khnglinquanti AE. Nhvyy l nhngMEtim nng,c th cha 54 gy hi cho bnh nhn nhng vn cn c pht hin v phn tch nguyn nhn m bo an ton hn cho ngi bnh. Cn c bit lu rng nhng nguyn nhn gy ra cc ME cha gy hi hoc mi gy hi nh trn bnh nhn thng cng s l nhng nguyn nhn dn n ME gy hi [43]. V ni xy ra phn ng, t l AE nghi ng lin quan n ME xy ra ngoi cngngcaohnsoviphnngxyraCSYTtngngvi2nghincu ca Tanti v Kumac. iuny c th phn nh phn no vai tr ca i ng nhn vin y t trong bnh vin trong vic gim thiu ME c kh nng gy ra AE. Lu rng t l ny c th vn cha phn nh c thc t do nhiu cc ME gy AE nh khng dn n vic bnh nhn nhp vin v do khng c bo co. Tuy nhin tlAEdoMExyraCSYTtrongnghincunycnkhcao(34,1%tng ngtltrongnghincucaTantil35,4%vcaosovi18%trongnghin cu ca ca Kumac) [38], [55].TlAEcxploinghimtrngcaotrongccboconghingc ME lin quan n AE v cc bo co AE c th l do vic u tin bo co cc AE nghim trng ca cn b y t, t dn n sai s m trong vic xc nh ME. T l ME khng gy ra AE gp trn bo co v AE nghim trng thp do c im ca AE khng phng trnh c thng l phn ng d ng, nht l cc phn ng nh trn da (nghin cu ca Kunac cng cho kt qu tng t [38]). Vic xc nh c nhiu ME (lin quan v khng lin quan n AE) trn cc bo co v AE t nghim trnghnsoviccbocovAEnghimtrngtrnmtmunghincum phn ln l AE nghim trng cng l mt bng chng cho thy t l ME trn thc t cthcncaohnna. Mtmt,tnhtrngnygykhkhnchovicphthin cc ME khi AE m n gy ra cha c nhn thc mt cch y , mt khc cng c ch li nht nh trong vic tp trung vo cc ME gy ra cc AE c ngha lm sng. Phn tch v xu hng trong CSDL Php cho thy t l cc bo co v AE nghim trng c chiu hng gia tng theo thi gian, do cc cn b y t nm bt cccAEthnggp,tnghimtrngvtptrunghnvonhngAEmi v/hoc c ngha lm sng [45]. 55 Phn tch su hn cho thy mt t l AE nghim trng rt cao lin quan n mtsloiMEnh:theodilmsng/cnlmsngkhngphhp;saing dng thuc; trnglptr liuv tin sdng (87-100%).T l ny cng ni bt khi so snh vi mt s loi ME v cch dng, liu, ch nh, tng tc (20-52,6%), l nhng loi ME m thng tin cn thit xc nh ME thng c bo co y trong a s cc bo co. Kt qu ny c th gi rng tn sut xut hin cc loi ME v theo di lm sng/cn lm sng, ng dng thuc, trng lp tr liu v tin s d ng trn thc t c th kh cao, nhng nghin cu t CSDL bo co ADR ch phthincmtslngtccMEthucnhngloikhi chnggyracc AEnghimtrngcnbytutinbocovbocomtcchchititcc thngtincnthit.cbit,tlAEnghimtrngchimas(83%)trongcc bo co c ME v bnh nhn t dng thuc k n cng gi mt tn sut ME cao hn na trong thc t, do ch khi AE xy ra kh nghim trngbnh nhnmi vo CSYT khm v iu tr ri t bo co v trng hp ca h c gi i. iu nycho thys cnthit phics thamgiaca chnh ngibnh voquytrnh bo co AE/ME nh c thc hin mt s quc gia trn th gii [43], mc d cthihistuyntruynvnngcaohiubitcaqunchngvlnhvc cnhgicdc.Nhiunghincucngchothyvaitrcabnhnhntrongh thng bo co cnh gic dc ang ngy cng tr nn quan trng [35], [57]. T chc c th b nh hng nhiu nht trong cc bo co nghi ng c mi quan h ME AE l ri lon da v m di da. Kt qu ny phn nh cc AE hay cghinhnnhttrongbocoADR.CcAEcnxtnghim lmsngxc nht c ghi nhntrong boco ADRni chung(0,140,79%) v nhngAE cn thm khm lm sng trnh chuyn mn su nh nh hng trn tim mch, pht trin tm thn, tr tu, thai nhi hu nhkhng ghi nhn [13]. Nh vy, c th trn thc t t l MEgy ra AE c nghalm sng ni trn c th cao,nhng v cn b y t cha nhn bit c nhng loi AE nn khng bo co. y l tnh trng in hnh ca mt CSDL bo co ADR vo thi k u pht trin [45]. 56 Nh vy, nhn chung c im ca cc AE c lin quan n ME phn tch ctrongnghincumangcthcaccAEccnbnhnvinytbo co trong c s d liu. Tuy nhin, nghin cu vn cho thy CSDL bo co ADR t nguyn ti Vit Nam l ngun d liu y tim nng khai thc pht hin cc sai st v cc bin c bt li c kh nng phng trnh c do lin quan n sai st . 57 CHNG 5. KT LUN V XUT KT LUN Nghin cu bc u pht hin v m t cc sai st lin quan n thuc cngnhmiquanhgiaccsaistvibincbtlitCSDLboco ADR, c th nh sau: 1. Tngs 152/763 (19,9%)boco ADR/AE c nhgi nghingc ME.Trongloisaistthnggpnhtlsaistvliudngvi65/152bo co,chim42,8%.Tiptheolccsaistvchnhvi45/152boco,chim 29,6%,bnhnhntdngthucknvi36/152boco,chim23,7%,cch dng vi 28/152 bo co, chim 18,4%, s dng thuc trn bnh nhn c tin s d ng thuc hoc nhm thuc vi 16/152 bo co, chim 10,5%. Trongccnhm thucc ME ghi nhn c, nhmkhngsinhchim i as(119boco,78,3%).Trongscckhngsinh,khngsinhhbetalactam (tng cng 52 bo co, chim 34,3%) l h dc l c ghi nhn nhiu nht. Bn cnh , nhm NSAIDs (11 bo co,7,2%) v cc thuc gim au h st khc (7 bo co, 4,6%) cng chim t l ng k. 2. 85/152 bo co nghi ng c ME c nh gi l c th hoc chc chn cmiquanhgiaMEphthincvAEcboco,chim11,1%trn tngs763bococnhgi.TrongccMEcnhgilcthl nguynnhngyraAEcbococsaistvchnh(n=38;44,7%),bnh nhn t dng thuc k n (n=35 ; 41,2%) v liu dng (n=18 ; 21,2%). TrongccAEnghinglhuqucaME,61,2%bococAEc nh gil nghimtrng. CcAEc ghi nhnnhiunht lccri lontrn davmdida(61,2%).Rilonhtiuha,tmthn,thnkinhvrilon tngqutcthchimmttlngk(14,118,8%).Tngs41/85boco (48,2%)cthngtinchothyphnngxuthinngoicngng)sovi29/85 bo co ti (34,1%) c s y t.58 Tngs8/10hdclhaygpnhttrongccMEnghinggyraAE cbocothucnhmkhngsinh,chimtngcng64/85(75,3%)boco. Ring cc beta-lactam ngoi penicillin chim 21/85 (24,7%) bo co. XUT nh gi, thngk v m tmt cchnhk,thngxuyn cc bo co ADR nhn c trung tm DI & ADR Quc gia pht hin tn hiu v ME v phn hi cho cc CSYT. Tiptcchunha,saiphngphpchophhpvitnhhnhVit NamcthavopdngmtcchthngquytiTrungtmDI&ADR Quc gia cng nh cc CSYT nhm pht hin cc ME nh hng cho vic ci thin thc hnh thuc m bo an ton cho bnh nhn. Xem xt sa i mubo co ADR hoc ban hnh mu bo co ring bit ghi nhn c cc thng tin chi tit hn v ME. TLTK 1 | TI LIU THAM KHO Ti liu tham kho ting Vit1. Ph Xun Anh (2010), Nghin cu nh gi mt s c s d liu thng dng trong thc hnh tra cu thng tin thuc ti Vit Nam, Kha lun tt nghip Dc s, trng i hc Dc H Ni.2. 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PL 2 | PL 3 | PH LC 2: B 20 TIU CH P METHOD CA WHOV CCH I CHIU DNG TRONG NGHIN CU B 20 tiu ch P method ca WHO: [61] Yutlin quan Tiu ch phng trnh cCKhngKhng r Khng p dng c Thchnh nghnghip (Professional practice PR)1. Sai liu? 2. Sai ng dng thuc? 3. Sai khong thi gian dng thuc 4. Sai dng thuc dng? 5. S dng thuc ht hn? 6. Lu tr thuc khng ng? 7. Li cch dng (thi gian, tc , khongcchdng,kthut,chun b, tin hnh, pha thuc)? 8. Ch nh sai 9.Knkhngphhptheoc imbnhnhn(tui,giitnh, mang thai, khc)? 10. K n khng ph hp vi tnh trnglmsngcabnhnhn(suy thn,suygan...)hocbnhl khc? 11.Tinsdngivithuc hoc nhm thuc s dng? 12. Tng tc thucthuc c PL 4 | xc nh? 13. Trng lp tr liu? (k nhiu hn 1 thuc vi thnh phn tng t) 14. Khng s dng thuc cn dng? 15. Hi chng cai thuc? (Do dng iu tr t ngt) 16.Theodilmsng/cnlm sng khng ph hp? Thuc/sn phm (Product/Drug Pd) 17. S dng thuc cht lng thp? 18. Thuc gi? Bnh nhn (Patient Pa) 19. Khng tun th? 20. T dng thuc k n? PL 5 | Cch i chiu dng trong nghin cu: Tiu ch phng trnh cMcchnhdng ichiutrongbo co Ti liu i chiu Sai liu?13.Hmlng,s lndngtrong ngy/tun/thng Chuyn lun thuc: nhgitheoch nhnusdng thuctheochnhc trong chuyn lun nhgitheo khonggiaccch nhnusdng thuckhngtheocc chnhctrong chuyn lun.Sai ng dng thuc?13. ng dng Saikhongthigiandng thuc 13. Ngy iu tr Sai dng thuc dng?13.Dngboch, hm lng S dng thuc ht hn?13.Nhsnxut;s l NA Lu tr thuc khng ng?NAChuyn lun thuc Licchdng(thigian,tc , khong cch dng, k thut, chun b, tin hnh, pha thuc) 7.Mtbiuhin ADR 13. S ln dng trong ngy/tun/thng Ch nh sai (a)13. L do dng thuc Knkhngphhptheo c im bnhnhn (tui, gii tnh, mang thai, khc)? 2.Ngysinhhoc tui.3. Gii tnh.4. Cn nng 8.Tins(dng, PL 6 | thainghn,nghin thucl,nghin ru, bnh gan, bnh thn) K n khng ph hp vi tnh trnglmsngcabnhnhn (suythn,suygan...)hoc bnh l khc? 8.Tins(dng, thainghn,nghin thucl,nghin ru, bnh gan, bnh thn) Tinsdngivithuc hoc nhm thuc s dng? 8.Tins(dng, thainghn,nghin thucl,nghin ru, bnh gan, bnh thn) Tngtcthucthuc c xc nh? (b) 13.Thuc(tngc v tn thng mi).16.Ccthucdng ngthi(Ngoitr ccthucdngiu tr/khcphchu qu ca ADR) PhnmmStockleys Drug Interaction. Trnglptrliu?(knhiu hn1thucvithnhphn tng t) (c) Khngsdngthuccn dng? NA Hichngcaithuc?(Do dng iu tr t ngt) 5.Ngyxuthin phn ng.7.Mtbiuhin ADR.13. Ngy iu tr.16.Ccthucdng ng thi.Chuyn lun thuc Theodilmsng/cnlm8.CcxtnghimChuyn lun thuc PL 7 | sng khng ph hp?linquannphn ng.S dng thuc cht lng thpNANA Thuc giNANA Khng tun th?NAChuyn lun thuc T dng thuc k n? (d)7.Mtbiuhin ADR Danhmcthuc khngknc banhnhkmtheo Thng t 08/2009/TTBYT (Ph lc 2) PL 8 | PH LC 3 :CC CP THUC C XEM LTRNG LP TR LIU[75] TheotiuchuncaHomeHealthCenter,sauylccthucthng dng c th gy ra AE nu v tnh c dng ng thi. S dng nhiu hn hoc bng 2 thuc cng thuc mt loi trong cc loi ny c tnh l trng lp tr liu: NSAIDs, tr aspirin 325mg Thuc gim au gy nghin Thuc chn th th H2