CABRERA (2007) Timing of Therapeutic Intervention

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    Rinifo ml R`atg{aqric Ifrat|afrimf BaratnifasLqfcrimfge gfb Sqt|i|ge Mqrcmnas if g Nmqsa

    Nmbae ml Egra Iflgfriea Dgrraf BisagsaNgtim G Cgdtatg.Sgegzgt7% Atic N Tmshaeeay7% Jia Dq7% Dtgbeay E @mboas7% Faesmf Yaw7% Jgnas C Bmboa7%Egnyg S S`i`gdqbbif7% Isr|gf Sm`gt4% Bg|ib A Seagr4% Tmfgeb H Sc`aqea7% Da|atey E Bg|ibsmf3%Safo @ C`afo7% [arat Emdae4 gfb Ngtcm G[gssifi7

    7Oafzyna Cmt{mtgrimf% Ltgnifo`gn% Ngssgc`qsarrs% QSG8 4Cafrat lmt Gb|gfcab Dimrac`fmemoy gfb Nabicifa% Tmdatr _mmb Jm`fsmf Nabicge Sc`mme%[iscgrgwgy% Faw Jatsay% QSG8 3Ba{gtrnafr ml Ifratfge Nabicifa% Qfi|atsiry ml Imwg Cmeeaoa ml Nabicifa% Imwg Ciry% Imwg% QSG

    Cegssicge egra ifgfriea faqtmfge catmib ei{mqscifmsis(cEIFCE) is g nmfmoafic bismtbat cgqsab dy r`a emssm rti{a{ribye {a{ribgsa 7 (R[[7) gcri|iry gs g tasqer m

    nqrgrimfs if CEF4& Gdsafca m R[[7 tasqers if eysmsmngesrmtgoa wir` gf gccmn{gfyifo gpmfge baoafatgrimfr`tmqo`mqr r`a cafrtge fat|mqs sysran (CFS)% w`ic`eagbs rm {tmotassi|a faqtmbaoafatgrimf gfb agtey bagr`&If r`is srqby% wa cmn{gtab r`a acgcias m {ta. gfb{msr.syn{rmngric ifjacrimfs m tacmndifgfr gbafm.gssmcigrab |itqs (GG\) mt rtagrifo r`a caeeqegt gfb qfc.rimfge gdfmtngeirias m CEF4 nqrgfr nica& Ifrtgctgfigeifjacrimf m GG\7.`CEF4 tasqerab if wibas{tagb `qngfR[[7 (`R[[7) gcri|iry if r`a dtgif r`gr wgs 7;7;;.mebgdm|a wieb.ry{a ea|aes& Ifjacrimfs damta bisagsa mfsar{ta|afrab srmtgoa gfb s{gtab faqtmfs tmn gpmfge

    baoafatgrimf% talacrab dy r`a {tasat|grimf m nmrmt qfcrimf& Lqtr`atnmta% r`a ngjmtiry m CEF4 nqrgfrnica rtagrab {ta.syn{rmngricgeey ei|ab mt gr eagsr33; bgys% cmn{gtab wir` g nabigf sqt|i|ge m 717 bgysif qfrtagrab CEF4 nqrgfr cmfrtmes& If cmfrtgsr% ger`mqo`ifjacrimf grat bisagsa mfsar gnaeimtgrab eysmsmnge srmt.goa% r`ata wgs a|ibafca m gpmfge baoafatgrimf% nmrmt

    qfcrimf s`mwab einirab tacm|aty% gfb r`a gfinges `gbg nabigf eias{gf m 47< bgys& R`asa bgrg ieeqsrtgra r`ain{mtrgfca m agtey ifrat|afrimf mt af`gfcab r`atg{aq.ric dafar% w`ic` ngy {tm|iba oqibgfca if basiofifofm|ae rtagrnafr srtgraoias mt cEIFCE {griafrs&

    Tacai|ab 7< G{tie 4;;?8 gcca{rab 49 Ngy 4;;?8 gb|gfcab mfeifa{qdeicgrimf ;; Nmfr` 4;;?& bmi:7;&7;30-sj&nr&

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    www&nmeacqegtr`atg{y&mto

    R`a Gnaticgf Smciary m Oafa R`atg{yGG\7 Oafa R`atg{y mt cEIFCE

    mfsar%7; a a|geqgrab rtagrnafr m {ta. gfb {msr.syn{rmngric

    CEF4 nqrgfr nica& Mqt tasqers s`m r`gr rtagrnafr gat bisagsa

    mfsar ir` r`a cmbmf m{rinizab GG\7.`CEF4 |acrmt {tm|ibab

    sq{atimt tasqers rm r`msa ta{mtrab {ta|imqsey ir` GG\ satmry{as.

    4% .1% gfb .t`7;& Nmtam|at% rtagrnafr damta mfsar m syn{rmns

    siofilcgfrey af`gfcab r`a r`atg{aqric tas{mfsa& Rasa lfbifos

    `g|a in{mtrgfr in{eicgrimfs mt r`a basiof m qrqta ceificge rtiges

    mt cEIFCE&

    tasqersrgn i i{g r[[7 dgiEysmsmnge {gr`memoy if r`a CEF4 nqrgfr nmqsa dtgif is baracrab

    gs agtey gs 1< aahs m goa8 r`a qfyiaebifo gfb {tmotassi|a faq.

    tmbaoafatgrimf r`gr meems tasqers if {tangrqta bagr`&< CEF4

    nqrgfr nica goab 2 aahs ({ta.syn{rmngric otmq{% f > 4;) mt gr

    77 aahs ({msr.syn{rmngric otmq{% f > 4;) ata ifjacrab if sip

    taoimfs m r`a dtgif ir` 7&; 7;7; oafmna cm{ias (oc) m GG\7.

    `CEF4 {at taoimf% mt g rmrge m 7; {at otmq{) mt g sqt|i|ge cm`mtr (f > 7; {at otmq{)& If r`a

    goa.ngrc`ab cm`mtr% gee r`a gfinges qfbatafr qfcrimfge rasrs

    damta daifo hieeab gr 79 aahs mt cmn{gtismf m ap{tassimf gfb

    {gr`memoy& @gfbeifo m r`a CEF4 nqrgfr nica% as{acigeey r`msa

    r`gr gta |aty syn{rmngric% cgf ifbqca grge saizqtas&< Rqs mt sqt.

    |i|ge gfgeysis% gfinges ata ea ir` nifinge bisrqtdgfca qfrie

    fgrqtge bagr`% mt r`ay ata hieeab air`at gr r`a afb m r`a srqby

    (gr gf if|asriogrmt.saeacrab 2? aahs) mt agteiat i nmtidqfb&

    Ifjacrimfs m GG\7.`CEF4 tasqerab if [[7 gcri|iry 7;7;;.

    meb gdm|a ieb.ry{a ea|aes r`tmqo`mqr r`a tmsrtmcgqbge gtag m

    r`a dtgif (Lioqta 7)& Ap{tassimf ea|aes ata assafrigeey r`a sgna

    if gfinges rtagrab gr 2 mt 77 aahs% banmfsrtgrifo r`gr g {egragq

    m `[[7 gcri|iry gs tagc`ab dy 79 aahs& [[7 ap{tassimf gs

    srgdea% gs r`a CEF4 nqrgfr nica tmn r`a sqt|i|ge otmq{ r`gr ata

    rtagrab gr 2 aahs gfb sgctilcab gr 2? aahs s`mab siniegt ea|.

    aes m [[7 gcri|iry rm r`a ea|aes gr 79 aahs& Gfgeysis m afzyna

    gcri|iry if r`a ei|at gr 2? aahs tmn r`a nqrgfr nica rtagrab gr

    2 aahs ifbicgrab r`gr ap{tassimf gs tasrticrab rm r`a dtgif&

    `[[7 ap{tassimf mdsat|ab dy innqfm`isrmc`anisrty cmttmdm.

    tgrab r`asa tasqers (Lioqta 4)& Tmdqsr [[7 innqfm.{msiri|a caees

    ata baracrab r`tmqo`mqr r`a dtgif if rtagrab gfinges gr dmr` 79

    gfb 2? aahs& Mdsat|grimf gr io` ngofilcgrimf if tanmra taoimfs

    s`mab g gifr% biqsa `[[7 {qfcrgra innqfm.srgififo {grratf%

    ifbicgrifo r`gr em ea|aes m `[7 ata bis{atsab r`tmqo`mqr r`a

    dtgif (bgrg fmr s`mf)&

    rgn gl gg gpg giGr 79 aahs% r`a famcmtrap% srtigrqn% gfb r`gegnqs taoimfs m r`a

    qfrtagrab CEF4 nqrgfr nmqsa dtgif cmfrgif `io` ea|aes m gqrm.

    qmtascafr srmtgoa ngratige (Lioqta 3)& @ma|at% 79.aah.meb

    gfinges rtagrab damta mt gat bisagsa mfsar s`mab g bactagsa

    if gqrmqmtascafr srmtgoa rm sqc` gf aprafr r`gr r`asa nica ata

    ifbisrifoqis`gdea tmn qfrtagrab ieb.ry{a nica (Lioqta 3)&

    Wqgfrirgri|a nargnmt{`ic gfgeysis s`mab r`gr ea|aes m srmtgoa

    ngratige if ieb.ry{a gfb rtagrab CEF4 nqrgfr nica ata eass

    r`gf 4;! m r`msa if r`a qfrtagrab CEF4 nqrgfr if gee apgnifab

    srtqcrqtas (Lioqta 3)& Tabqcrimf m srmtgoa gs ifba{afbafr m

    `ar`at r`a nica ata rtagrab gr 2 mt 77 aahs& Gr 2? aahs% ea|.aes m gqrmqmtascafr srmtgoa ngratige gs sriee em if r`a CEF4

    R`a Gnaticgf Smciary m Oafa R`atg{y

    7;;%;;;

    1;%;;;

    7;%;;;

    R[[7gcri|iry(LQ-nif-no)

    1%;;;

    2%;;;

    3%;;;

    4%;;;

    7%;;;

    ;E7 E4 E3 E2 E1 T7 T4 T3 T2 T1 Ei|

    Li 7 ri{{i {{ig 7 (r[[7) gi|i g dgi iji GG\7.cef4&G sc`angric ta{tasafrgrimf m r`a ifjacrimf siras gfbr`a cmttas{mfbifo dtgif segds gemfo r`a tmsrtmcgqbge gpis ba{icrs r`aifjacrimf siras if r`a tio`r (T7T1) gfb ear (E7E1) `anis{`atas& R`aei|at (Ei|) gs gesm gfgeyzab& Hay: qfrtagrab ieb.ry{a nica (f > 2% m{afcitceas)8 77.aah.rtagrab CEF4 nqrgfr nica gr 79 aahs (f > 3% m{afswqgtas)8 gfb 2.aah.rtagrab CEF4 nqrgfr nica gr 2? aahs (f > 2%eeab citceas)& Gcri|iry if r`a qfrtagrab nqrgfr nica gs ir`if r`a dgch.otmqfb |geqas m r`a gssgy gfb is fmr s`mf& Fmra r`gr ieb.ry{a nica gr79 aahs gfb 2? aahs m goa `gb ifbisrifoqis`gdea gcri|irias gfb r`qsgta otmq{ab& Bgrg gta {tasafrab gs nagf SAN& GG\% gbafm.gssmcigrab|itqs8 `CEF4% `qngf CEF4&

    g

    Ealr anis{`ata Tio`r anis{`ata

    d

    c

    Li 4 r ng i{{i {{ig 7 p{i {g i dgi cef4 ng ni&(g) Gfinges rtagrab gr 77 aahs gfbgfgeyzab gr 79 aahs8 (d) gfinges rtagrab gr 2 aahs gfb gfgeyzab gr79 aahs8 (c) gfinges rtagrab gr 2 aahs gfb gfgeyzab gr 2? aahs& Scgeadgt% 4&; nn&

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    Nmeacqegt Ratg{y

    R`a Gnaticgf Smciary m Oafa R`atg{yGG\7 Oafa R`atg{y mt cEIFCE

    nqrgfr nica rtagrab gr 2 aahs% ger`mqo` if smna taoimfs m r`a

    dtgif srmtgoa gs seio`rey aea|grab cmn{gtab ir` r`a awqi|geafr

    gfinges gfgeyzab gr 79 aahs (Lioqta 3)& Taogtbeass% r`a 2?.

    aah.meb gfinges `gb siofilcgfrey eass srmtgoa ngratige r`gf r`a

    79.aah.meb qfrtagrab CEF4 nqrgfr cmfrtme nica&

    If {ta|imqs srqbias% gnifm cq{tic sie|at srgififo ta|ageab sqd.

    srgfrige gpmfge baoafatgrimf if r`a dtgif m CEF4 nqrgfr nica&

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    R`a Gnaticgf Smciary m Oafa R`atg{yGG\7 Oafa R`atg{y mt cEIFCE

    mccqttab gr 7< gfb 70 aahs if r`a qfrtagrab gfb 77.aah.rtagrab

    CEF4 nqrgfr nica (Lioqta

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    Nmeacqegt Ratg{y

    R`a Gnaticgf Smciary m Oafa R`atg{yGG\7 Oafa R`atg{y mt cEIFCE

    nqrgfr otmq{ gs siofilcgfrey grrafqgrab cmn{gtab ir` r`a 721.

    bgy.meb qfrtagrab nqrgfrs gfb r`a 70

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    R`a Gnaticgf Smciary m Oafa R`atg{yGG\7 Oafa R`atg{y mt cEIFCE

    r`asa biatafcas& Taogtbeass% r`a cqttafr srqby ifjacrab eass GG\7

    |acrmt (;&< 7;77 oc {at nmqsa) r`gf GG\t`&7; (7&< 7;77 oc {at

    nmqsa) ir` sq{atimt dafalr% sqooasrifo r`a cg{gciry m GG\7.

    `CEF4 rm gc`ia|a otagrat r`atg{aqric acgcy ir` eass |itimf&

    If cmfceqsimf% GG\7.nabigrab `[[7 afzyna ta{egcanafr

    gs io`ey aacri|a if rtagrifo r`a caeeqegt {gr`memoy gfb r`a qfc.

    rimfge {`afmry{a m r`a CEF4 nqrgfr nmqsa nmbae m cEIFCE&

    tagrnafr damta bisagsa mfsar {tm|ibab g sq{atimt r`atg{aqric

    dafalr rm rtagrnafr gat faqtm{gr`memoy gs aee asrgdeis`ab

    if r`a dtgif& Rasa bgrg sqooasr r`gr r`a einirifo gcrmt mt a.

    cgcy is r`a {ta|afrimf m itta|atsidea {`afmry{as sqc` gs gpmfge

    baoafatgrimf gfb banmfsrtgra r`a in{mtrgfca m agtey ifrat|af.

    rimf mt gc`ia|ifo af`gfcab r`atg{aqric dafalr& If ratns m GG\.

    nabigrab rtagrnafr m cEIFCE% tasqers m r`is srqby sqooasrs r`gr

    a|af r`mqo` gs{acrs m caeeqegt {gr`memoy cgf da ta|atsab dy oafa

    r`atg{y% r`ata gta gbbirimfge gs{acrs m r`a bisagsa r`gr bicrgra

    {tmotassimf gfb a|afrqge eias{gf& Rqs rtagrnafr m {griafrs `m

    gta air`at {ta.syn{rmngric mt s`m mfey nieb syn{rmns m r`a

    bisagsa ngy da faabab mt dasr r`atg{aqric mqrcmna&

    NGratIGes Gfb Nar`mbsGG\ |acrmt& Ra `qngf [[I {tmraif (gccassimf fqndat GL;7?21 4;) gfb 77 aahs

    (f > 4;) ata ifjacrab dy sratamrgcric sqtoaty ifrm r`a srtigrqn (;&1;%

    7&1;% gfb 4&;; nn)% `i{{mcgn{qs (4&;;% 7&?1% gfb 7&?1 nn)% gfb

    baa{ catadaeegt fqceaqs (1&01% 7&1;% gfb 4&41 nn) m r`a tio`r `ani.

    s{`ata% gfb ifrm r`a nmrmt cmtrap (7&;;% 7&41% gfb 7&41 nn)% r`gegnqs

    (4&;;% 7&?1% gfb 3&41 nn) gfb nabqeeg (1&01% 7&1;% gfb 3&1; nn)

    m r`a ea `anis{`ata& Agc` ifjacrimf sira tacai|ab 7&; 7; 7; oc (3 e) m

    GG\7.`CEF4 mt g rmrge m

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    Nmeacqegt Ratg{y

    R`a Gnaticgf Smciary m Oafa R`atg{yGG\7 Oafa R`atg{y mt cEIFCE

    1& [genat% BF% Lagtfeay% IN% Nabb% SN% _gehat% JA% Ngtrifqs% TB% Dgyeiss % SE ar ge&(7909)& Eysmsmnge srmtgoa m r`a BCCB tagcri|a {tmramei{ib sqdqfir m nirmc`mfbtige

    GR[ syfr`gsa if qngf gfb m|ifa catmib ei{mqscifmsas& Gb| Ap{ Nab Dime4