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N)-4.8(e)-1.7(w )35.9(Y)97(o)-5.4(rk)-5.4(: Un)-5.4(ited)-5.4( N)-4.8(a)-1.7(tio)-5.4(ns; )-6(201)-5.4(0. )]TJ -2.8743 -1.1497 TD -.0017 Tc -.0028 Tw [( )-1053.9(2 )-652.7(In)-4.7(tern)-4.7(ation)-4.7(a)-1(l Narco)-4.7(tics )-6(C)6.6(o)-4.7(n)-4.7(t)6.7(rol )-6(Bo)-4.7(ard)-4.7(.)-3.2( Psycho)-4.7(tro)-4.7(p)-4.7(i).7(c Sub)-4.7(s)-1.8(tan)-4.7(ces: )-6( Statistic)-7(s )-6(fo)-4.7(r 20)-4.7(09)-4.7(. )-6(New )29.9(Y)103.7(o)1.3(rk)-4.7(: Un)-4.7(ited )]TJ 2.8743 -1.1497 TD -.0026 Tc .0041 Tw [(N)-5(a)-1.9(tio)-5.6(ns; 201)30.3(1. )]TJ -2.8743 -1.1437 TD .0012 Tc .0003 Tw [( )-1047.9(3)4.2( )-646.7(Petersen)4.2( )59.9(A. )6(Da)7.9(wn)4.2( o)4.2(f)-1.1( a)7.9( ne)7.9(w sl)9.6(eep )6(dr)4.9(u)4.2(g)10.2(?)-10( )]TJ /TT16 1 Tf 18.6347 0 TD -.0024 Tc .0039 Tw [(W)94.1(a)-5.4(ll S)-5.4(t)0(r)33.5(eet Jo)-5.4(urna)-5.4(l)]TJ /TT10 1 Tf 7.6826 0 TD [( 201)30.5(1 Ju)-5.4(l )6(19)-5.4(;D1)-5.4(-)1.3(D)-4.8(4).6(. )]TJ -26.3174 -1.1497 TD .0001 Tc .0014 Tw [( )-1047.9(4 )-646.7(Ahm)11.5(a).8(d R, Bat)8.5(h)-2.9( )6(P)89.2(A)3.7(. Ide)6.8(n)-2.9(tification )6(of ris)6(k)-2.9( fa)6.8(ct)]TJ 20.8144 0 TD .0005 Tc .001 Tw [(ors )6(for )6(15-ye)7.2(a)1.2(r m)11.9(o)-2.5(rtality am)11.9(ong com)5.9(m)11.9(unity-dwelling ol)8.9(der )]TJ -17.9401 -1.1497 TD .0013 Tc .0002 Tw [(peo)4.3(p)-1.7(l)3.7(e)2( )6(usi)3.7(n)4.3(g C)9.6(o)-1.7(x)4.3( re)8(gre)8(ssi)3.7(o)4.3(n)-1.7( a)8(n)-1.7(d)4.3( a )6(genet)3.7(i)3.7(c)2( al)9.7(go)4.3(ri)3.7(t)3.7(h)-1.7(m)12.7(.)-.2( )]TJ /TT16 1 Tf 21.479 0 TD .0016 Tc -.0001 Tw [(J Ger)43.5(ont)10(ol)4( )18(A)19.6( Bi)10(ol)4( )6(Sc)8.3(i)4( Med )6(Sci)]TJ /TT10 1 Tf 11.9581 0 TD -.003 Tc -.0015 Tw [( 2)-6(005; )-6(6)-6(0)0(A)-5.4(:)-.6(105)-6(2-1)-6(0)0(5)-6(8)0(. )]TJ -36.3114 -1.1437 TD .0016 Tc -.0001 Tw [( )-1047.9(5)4.6( )-646.7(Al)4(l)4(gul)4(a)8.3(nde)8.3(r C)3.9(,)6.1( Lj)4(u)4.6(n)-1.4(g)4.6(b)-1.4(er)23.2(g )6(L, )6(Fi)4(sher)5.3( L)7.7(D)-.8(. L)7.7(o)4.6(ng)4.6(-t)4(erm)13( pr)5.3(og)4.6(n)4.6(o)-1.4(si)4(s i)4(n)4.6( ad)4.6(di)4(ct)4(i)4(o)4.6(n )6(on)4.6( se)8.3(dat)4(i)4(v)-1.4(e a)8.3(n)-1.4(d)4.6( hy)10.6(pn)4.6(ot)4(i)4(c)2.3( d)4.6(r)5.3(ugs)7.5( )]TJ 2.8743 -1.1497 TD .0003 Tc .0012 Tw [(analyzed )6(with t)8.7(h)-2.7(e C)8.6(o)-2.7(x re)7(gres)6.2(s)6.2(i)2.7(on m)11.7(odel. )]TJ /TT16 1 Tf 16.5449 0 TD .0016 Tc -.0001 Tw [(Act)4(a)-1.4( Psyc)8.3(hi)4(at)4(r)7.5( Sc)8.3(an)4.6(d)]TJ /TT10 1 Tf 8.5988 0 TD -.0032 Tc -.0013 Tw [( 19)-6.2(87)-6.2(; 7)-6.2(5)-.2(\(5\))-5.5(:)-.8(52)-6.2(1-)-5.5(531)-6.2(. )]TJ -28.018 -1.1497 TD -.002 Tc .0035 Tw [( )-1047.9(6 )-646.7(Bellev)-5(ille G)-4.4(.)-3.5( )6(Mo)-5(rtality h)-5(azard associated)-5( )6(w)-4.4(ith)-5( an)-5(x)-5(i)6.4(o)-5(l).4(ytic and)-5( )6(h)-5(ypn)-5(o)-5(tic )6(d)-5(r)1.7(ug)-5( )6(u)-5(s)-2.1(e in th)-5(e n)-5(a)-1.3(tion)-5(a)-1.3(l popu)-5(latio)-5(n)-5( )]TJ 2.8743 -1.1437 TD .0002 Tc .0013 Tw [(health s)6.1(u)-2.8(rvey)69.1(. )]TJ /TT16 1 Tf 5.7844 0 TD -.0001 Tc .0016 Tw [(Can J Psyc)6.6(hiat)8.3(ry)]TJ /TT10 1 Tf 6.8743 0 TD -.0031 Tc .0046 Tw [( 201)-6.1(0)-6.1(;)-.7( )6(55)-6.1(\(9)-6.1(\))-5.4(:)5.3(1)-6.1(37-)-5.4(146)-6.1(. )]TJ -15.5329 -1.1497 TD -.0014 Tc .0029 Tw [( )-1047.9(7 )-646.7(Brabb)-4.4(i)1(n)-4.4(s)4.5( CJ, )6(Dewey ME, C)6.9(opelan)-4.4(d)-4.4( RM, David)-4.4(s)-1.5(on)-4.4( )6(IA)]TJ 24.4252 0 TD -.001 Tc .0025 Tw [(, McW)32.7(illiam)10.4( C, Sau)-4(n)2(d)-4(e)5.7(rs )6(P)34.2( et al. )6(In)-4(so)-4(m)10.4(n)-4(ia in)-4( the )]TJ -21.5509 -1.1497 TD -.0013 Tc .0028 Tw [(eld)-4.3(e)-.6(rly: Prev)-4.3(al)7.1(en)-4.3(ce, )6(g)-4.3(e)5.4(n)-4.3(d)-4.3(e)5.4(r )6(d)-4.3(i)7.1(f)14.3(f)-3.6(eren)-4.3(ces and)-4.3( )6(relatio)-4.3(n)-4.3(s)-1.4(h)-4.3(i)7.1(p)-4.3(s)-1.4( )6(with)-4.3( m)10.1(o)-4.3(rb)-4.3(id)-4.3(ity an)-4.3(d m)10.1(o)-4.3(rtality)67.6(. )]TJ /TT16 1 Tf 35.0778 0 TD -.0001 Tc .0016 Tw [(Int J )6(Ger P)6(s)-.2(ych)]TJ /TT10 1 Tf 6.2395 0 TD 0 Tc 0 Tw ( )Tj -41.3174 -1.1437 TD -.0031 Tc .0046 Tw [(1)-6.1(993)-6.1(; 8)-6.1(:)5.3(4)-6.1(73-)-5.4(480)-6.1(. )]TJ -2.8743 -1.1497 TD -.0002 Tc .0017 Tw [( )-1047.9(8 )-646.7(Fukuha)6.5(ra S, )6(Green J)5.7(,)-1.7( )59.9(Albe)6.5(rt J, Mi)]TJ 16.1377 0 TD -.0004 Tc .0019 Tw [(hara )6(H, Pis)5.5(oni R)7.9(,)-1.9( )35.9(Y)99(a).3(m)11(azaki S et al. Sy)]TJ 15.3054 0 TD .0009 Tc -.0054 Tw [(mptom)12.3(s).8( )-6(of de)7.6(pre)7.6(ssion, presc)7.6(r)-1.4(ipt)9.3(i)3.3(on of )]TJ -28.5689 -1.1497 TD 0 Tc .0015 Tw [(benz)6.7(odiazepi)8.4(n)3(es, a)6.7(n)-3(d the )6(risk of )6(death )]TJ 15.497 0 TD .0001 Tc .0014 Tw [(i)8.5(n)-2.9( )6(he)6.8(m)11.5(odialysis patients in Japa)6.8(n. )]TJ /TT16 1 Tf 13.6826 0 TD .0005 Tc -.005 Tw (Kidney Int)Tj /TT10 1 Tf 4.1916 0 TD -.0031 Tc -.0014 Tw [( 20)-6.1(06)-6.1(; )-6(70\()-5.4(10)-6.1(\))-5.4(:)5.3(1)-6.1(866-)-5.4(187)-6.1(2. )]TJ -36.2455 -1.1437 TD -.0015 Tc .003 Tw [( )-1047.9(9 )-646.7(Hau)-4.5(s)4.4(k)-4.5(e)5.2(n)-4.5( )59.9(AM, )6(Sku)-4.5(r)-3.8(t)6.9(v)-4.5(eit S, )18(Tverd)-4.5(a)-.8(l )59.9(A. Use )6(o)-4.5(f)2.2( anx)-4.5(i).9(o)-4.5(l).9(ytic o)-4.5(r)2.2( hyp)-4.5(no)-4.5(tic drug)-4.5(s )6(an)-4.5(d to)-4.5(tal m)9.9(o)-4.5(rtality in)-4.5( a g)-4.5(e)5.2(n)-4.5(e)-.8(ral )]TJ 2.8743 -1.1497 TD -.0026 Tc -.0019 Tw [(mid)-5.6(d)-5.6(l)-.2(e-)-4.9(ag)-5.6(ed)-5.6( po)-5.6(pu)-5.6(latio)-5.6(n. )]TJ /TT16 1 Tf 10.012 0 TD -.0041 Tc .0056 Tw [(Pharm)-6.5(a)-7.1(co)-7.1(ep)-7.1(id)-7.1(em)-6.5(i)4.3(o)-7.1(l D)-6.5(r)1.8(ug)-7.1( )6(Sa)-7.1(f)]TJ /TT10 1 Tf 11.9641 0 TD .0027 Tc -.0012 Tw [( 2)5.7(0)5.7(07;)5.1( )6(1)5.7(6)-.3(\()6.4(8)-.3(\):)11.1(91)5.7(3)5.7(-)6.4(91)5.7(8.)7.2( )]TJ -24.8503 -1.1497 TD -.0015 Tc .003 Tw [( )-544.9(1)-4.5(0)1.5( )-646.7(Hays JC, Blazer DG, Fo)-4.5(ley DJ. Risk)-4.5( )6(of )6(n)-4.5(a)-.8(ppin)-4.5(g)-4.5(:).9( ex)-4.5(cessive )6(d)-4.5(a)-.8(yti)-5.1(m)9.9(e sleep)-4.5(in)-4.5(ess and)-4.5( m)9.9(o)-4.5(rtality in)-4.5( an)-4.5( o)-4.5(l)6.9(d)-4.5(e)-.8(r )]TJ 2.8743 -1.1437 TD .0022 Tc -.0007 Tw [(com)7.6(m)13.6(uni)4.6(t)4.6(y)5.2( po)5.2(pul)4.6(at)4.6(i)4.6(o)5.2(n. )]TJ /TT16 1 Tf 9.5689 0 TD -.0004 Tc -.0041 Tw [(J)6.3( )12(A)5.6(m)-2.8( Geriatr Soc)]TJ /TT10 1 Tf 6.9341 0 TD .003 Tc -.0075 Tw [( 19)6(96;)5.4( 4)6(4)0(:)5.4(6)6(93)6(-)6.7(6)0(9)6(8)6(.)1.5( )]TJ -19.3772 -1.1497 TD -.0012 Tc .0027 Tw [( )-586.8(1)37.7(1)1.8( )-646.7(Hedn)-4.2(er J, Caidah)-4.2(l K, Sjo)-4.2(l)1.2(and)-4.2( )6(H, )6(Karlsson)-4.2( )24(T)70.7(,)-2.7( )6(Herlitz )]TJ 23.7006 0 TD -.0016 Tc .0031 Tw [(J. )6(Sleep h)-4.6(a)5.1(b)-4.6(its and)-4.6( t)6.8(h)-4.6(eir asso)-4.6(ciatio)-4.6(n with)-4.6( m)9.8(o)-4.6(rtalit)-5.2(y d)-4.6(u)-4.6(r)-3.9(i)6.8(n)-4.6(g )]TJ -20.8263 -1.1437 TD .0015 Tc 0 Tw [(5-y)4.5(ear)5.2( f)5.2(o)-1.5(l)3.9(l)3.9(o)4.5(w-)5.2(up)4.5( aft)3.9(e)2.2(r)5.2( co)4.5(r)5.2(ona)8.2(ry)4.5( art)3.9(e)2.2(ry)4.5( )6(by)4.5(pas)7.4(s)1.4( su)4.5(r)17.1(g)-1.5(e)8.2(r)-.8(y)70.4(.)0( )]TJ /TT16 1 Tf 21.8204 0 TD -.0006 Tc -.0039 Tw [(Act)7.8(a)-3.6( Car)41.3(d)-3.6(iol)]TJ /TT10 1 Tf 5.1437 0 TD -.0034 Tc -.0011 Tw [( 2)-6.4(002)-6.4(; 5)-6.4(7)-.4(\(5)-6.4(\))-5.7(:)-1(341)-6.4(-34)-6.4(8)-.4(. )]TJ -29.8383 -1.1497 TD -.0018 Tc .0033 Tw [( )-544.9(1)-4.8(2)1.2( )-646.7(Hof)13.8(f)-4.1(m)9.6(a)-1.1(n)-4.8(n)-4.8( )24(VP)105.3(, )6(Do)-4.8(ssenb)-4.8(a)-1.1(ch)-4.8( M)7.1(,)-3.3( )24(W)73.8(e)-1.1(st )18(TM, Lowry )59.9(AJ. Mortality in)-4.8( a coho)-4.8(rt )6(o)-4.8(f)1.9( ou)-4.8(tp)-4.8(atien)-4.8(t).6(s )6(with)-4.8( sch)-4.8(i).6(zoph)-4.8(ren)-4.8(i).6(a: )]TJ 2.8743 -1.1497 TD -.0016 Tc .0031 Tw [(3)-4.6(-)-3.9(year ou)-4.6(tco)-4.6(m)9.8(es fro)-4.6(m)9.8( th)-4.6(e In)-4.6(tercon)-4.6(tin)-4.6(en)-4.6(tal Ou)-4.6(t)6.8(p)-4.6(atien)-4.6(t)]TJ 21.3174 0 TD .0017 Tc -.0002 Tw [( H)5.3(e)2.4(a)8.4(l)4.1(t)4.1(h)-1.3( O)5.3(u)-1.3(t)4.1(c)2.4(om)13.1(es St)4.1(udy)4.7( )6(\(IC)10(-S)7(O)5.3(H)-.7(O)5.3(\))-.6(. B)4(i)10.1(ol)4.1( Psy)4.7(c)8.4(hi)4.1(at)4.1(ry)4.7( )]TJ -21.3174 -1.1437 TD .0015 Tc 0 Tw [(61)4.5([)5.2(8)-1.5(S,)6( )53.9(A)5.1(b)-1.5(st)3.9(rac)8.2(t)3.9( Su)4.5(ppl)3.9(em)12.9(ent)3.9(])5.2(, 16)4.5(3S)6.8(-1)4.5(6)4.5(4)-1.5(S.)6( 2)4.5(0)4.5(0)-1.5(7)4.5(.)0( )6( )]TJ -2.8743 -1.1497 TD -.0013 Tc .0028 Tw [( )-544.9(1)-4.3(3)1.7( )-646.7(H)-3.7(u)1.7(b)-4.3(lin)-4.3( C)7(,)-2.8( Partin)-4.3(en M, )6(K)-3.7(o)1.7(sk)-4.3(env)-4.3(u)1.7(o)-4.3( M, K)-3.7(a)5.4(prio J. )]TJ 21.9401 0 TD -.0019 Tc .0034 Tw [(Sleep)-4.9( and)-4.9( mo)-4.9(rtality: a p)-4.9(opulatio)-4.9(n)-4.9(-)1.8(b)-4.9(a)-1.2(sed )6(2)-4.9(2)1.1(-year )6(fo)-4.9(llow)-4.3(-)1.8(up)-4.9( )]TJ -19.0659 -1.1497 TD .0017 Tc 0 Tw [(st)4.1(udy)70.6(. )]TJ /TT16 1 Tf 2.5988 0 TD -.0003 Tc (Sleep)Tj /TT10 1 Tf 2.1617 0 TD -.0029 Tc .0044 Tw [( 200)-5.9(7)-5.9(;)-.5( )6(30)-5.9(\(10)-5.9(\))-5.2(:1245)-5.9(-12)-5.9(5).1(3)-5.9(.)1.6( )]TJ -7.6347 -1.1437 TD -.0002 Tc .0017 Tw [( )-544.9(14 )-646.7(Isacs)5.7(on D, Carsjo K, Be)6.5(r)15.4(g)-3.2(m)11.2(a).5(n )6(U, Blac)6.5(kburn JL. )6(L)]TJ 22.8563 0 TD -.0001 Tc .0016 Tw [(ong-term)11.3( use)6.6( of )6(benz)6.6(odiazepin)]TJ 12.3353 0 TD -.001 Tc .0025 Tw [(es)4.9( in a)5.7( Swedis)4.9(h c)5.7(o)-4(mm)10.4(u)-10(n)-4(ity: )]TJ -32.3174 -1.1497 TD -.0015 Tc .003 Tw [(an)-4.5( eigh)-4.5(t-year fo)-4.5(llo)-4.5(w-u)-4.5(p)1.5(. )]TJ /TT16 1 Tf 9.9281 0 TD -.0024 Tc .0039 Tw [(J Clin)-5.4( Ep)-5.4(id)-5.4(emio)-5.4(l)]TJ /TT10 1 Tf 6.7665 0 TD .0029 Tc -.0074 Tw [( 1)5.9(9)5.9(92;)5.3( 4)5.9(5)-.1(\()6.6(4)-.1(\):)11.3(42)5.9(9)5.9(-)6.6(43)5.9(6.)7.4( )]TJ -19.5689 -1.1497 TD .0017 Tc -.0002 Tw [( )-544.9(15)4.7( )-646.7(Ko)4.7(ji)4.1(m)13.1(a)2.4( M)4.6(,).2( )24(W)71.3(a)8.4(kai)4.1( K)5.3(,).2( )6(Kawam)13.1(u)-1.3(ra)8.4( )18(T)73.6(,)6.2( )18(T)73.6(a)2.4(m)13.1(a)2.4(kos)7.6(hi)4.1( )59.9(A, )59.9(A)5.3(oki)4.1( R)10(,).2( )6(Li)4.1(n )41.9(Y)35.2( et)4.1( al)4.1(.)6.2( Sl)4.1(e)8.4(e)2.4(p )6(pat)4.1(t)4.1(e)2.4(rns)7.6( an)4.7(d)4.7( t)4.1(o)-1.3(t)4.1(a)2.4(l)4.1( m)13.1(o)-1.3(rt)4.1(al)4.1(i)4.1(t)-1.9(y:)4.1( a )]TJ 2.8743 -1.1437 TD .0015 Tc 0 Tw [(12)4.5(-y)4.5(ear )6(f)5.2(o)-1.5(l)3.9(l)3.9(o)-1.5(w)5.1(-)-.8(u)4.5(p)-1.5( st)9.9(udy)4.5( i)9.9(n)-1.5( Ja)8.2(pan)4.5(.)0( )]TJ /TT16 1 Tf 13.7006 0 TD .0005 Tc -.005 Tw [(J Epi)8.9(d)-2.5(emi)8.9(o)-2.5(l)]TJ /TT10 1 Tf 4.7904 0 TD -.0031 Tc .0046 Tw [( 200)-6.1(0)-6.1(;)-.7( )6(10)-6.1(\(2)-6.1(\))-5.4(:)5.3(8)-6.1(7)-.1(-9)-6.1(3. )]TJ -21.3653 -1.1497 TD .0015 Tc 0 Tw [( )-544.9(16)4.5( )-646.7(Kri)9.9(pke)8.2( D)5.1(F)78.6(,)6( Si)9.9(m)12.9(ons R)3.8(N)-.9(, )6(Ga)8.2(rf)5.2(i)3.9(nkel)3.9( L)7.6(,)0( )6(Ham)6.9(m).9(on)4.5(d )6(EC)3.8(. S)6.8(h)4.5(ort)3.9( )6(and)4.5( l)3.9(o)4.5(ng)4.5( sl)3.9(eep)4.5( )6(and)4.5( sl)3.9(eepi)9.9(n)-1.5(g)4.5( pi)9.9(l)3.9(l)3.9(s)1.4(:)3.9( Is i)3.9(n)-1.5(crea)8.2(se)8.2(d )]TJ 2.8743 -1.1497 TD -.0009 Tc .0024 Tw [(m)10.5(o)-3.9(rtality associated?)-12.1( )]TJ /TT16 1 Tf 8.7066 0 TD .0013 Tc -.0058 Tw [(Ar)37.2(c)8(h)-1.7( Ge)8(n )-6(Psyc)8(hi)3.7(at)3.7(ry)]TJ /TT10 1 Tf 8.3293 0 TD -.0027 Tc .0042 Tw [( 19)-5.7(79)-5.7(; )6(3)-5.7(6).3(\(1)-5.7(\))-5(:)-.3(103-)-5(1)36.2(1).3(6)-5.7(.)1.8( )]TJ -19.9102 -1.1437 TD .0003 Tc .0012 Tw [( )-544.9(17 )-646.7(Kri)8.7(pke)7( DF)77.4(, Kl)8.7(aube)7(r MR, )24(W)34(i)8.7(nga)7(rd )6(DL, )6(Fell RL, )59.9(Assm)11.7(us)]TJ 25.1198 0 TD -.001 Tc .0025 Tw [( JD, )6(Garfinkel L. Mortality)]TJ 10.8024 0 TD -.0004 Tc .0019 Tw ( hazard associ)Tj 5.6048 0 TD -.0005 Tc -.004 Tw (ated with )Tj -38.6527 -1.1497 TD .0021 Tc -.0066 Tw [(presc)8.8(r)-.2(i)4.5(p)-.9(t)4.5(i)4.5(o)5.1(n hy)11.1(pn)5.1(ot)4.5(i)4.5(c)2.8(s. )]TJ /TT16 1 Tf 9.4012 0 TD -.0012 Tc .0027 Tw [(Bi)7.2(o)-4.2(l)1.2( Psych)-4.2(ia)-4.2(try)]TJ /TT10 1 Tf 6.1796 0 TD -.003 Tc -.0015 Tw [( 19)-6(98; )-6(4)-6(3)-6(:)5.4(6)-6(87-)-5.3(693)-6(. )]TJ -18.4551 -1.1497 TD -.0017 Tc .0032 Tw [( )-544.9(1)-4.7(8)1.3( )-646.7(Kri)6.7(p)-4.7(k)-4.7(e)5( DF)75.4(, Garfink)-4.7(el L, )24(W)32(i)6.7(ng)-4.7(ard)-4.7( )6(DL, Klaub)-4.7(e)-1(r MR, Ma)]TJ 24.9521 0 TD -.0009 Tc .0024 Tw [(rler MR. M)8(o)-3.9(rtality asso)-3.9(ciated)-3.9( )6(wi)7.5(th)-3.9( sleep du)-3.9(rati)7.5(o)-3.9(n)2.1( and)-3.9( )]TJ -22.0778 -1.1437 TD -.0006 Tc 0 Tw [(in)-3.6(so)-3.6(m)10.8(n)-3.6(ia. )]TJ /TT16 1 Tf 4.1617 0 TD .0015 Tc [(Ar)37.4(c)8.2(h)4.5( Ge)8.2(n Psyc)8.2(hi)3.9(at)3.9(r)7.4(y)]TJ /TT10 1 Tf 8.3293 0 TD -.0029 Tc .0044 Tw [( 20)-5.9(02)-5.9(; )6(5)-5.9(9).1(\(2)-5.9(\))-5.2(:)5.5(1)-5.9(31-)-5.2(136)-5.9(. )]TJ -15.3653 -1.1497 TD -.0009 Tc .0024 Tw [( )-544.9(19 )-646.7(Lack LC)7.4(, Prior K, Luszcz M. )6(708. Does i)7.5(n)-3.9(som)10.5(n)-3.9(ia )]TJ 22.8323 0 TD -.0004 Tc .0019 Tw [(kill the elderly)14.6(?)-11.6( Slee)6.3(p )6(29[A)]TJ 11.0359 0 TD -.0007 Tc .0022 Tw [(bstract Supplem)10.7(e)0(nt], )53.9(A240. )]TJ -30.994 -1.1497 TD -.0012 Tc -.0033 Tw [(2)-4.2(006)-4.2(. )]TJ -2.8743 -1.1437 TD -.0016 Tc .0031 Tw [( )-544.9(2)-4.6(0)1.4( )-646.7(Mallo)-4.6(n)-4.6( L, Broman)-4.6( J-E, )6(Hetta J. Sleep)-4.6( co)-4.6(m)9.8(p)-4.6(lain)-4.6(ts pr)]TJ 23.4551 0 TD -.0013 Tc .0028 Tw [(ed)-4.3(ict coron)-4.3(a)-.6(ry artery )6(disease m)10.1(o)-4.3(rtalit)-4.9(y in)-4.3( m)10.1(a)-.6(les: a 1)-4.3(2)-4.3(-)]TJ -20.5808 -1.1497 TD -.0018 Tc .0033 Tw [(year)-4.1( fo)-4.8(llo)-4.8(w-u)-4.8(p)1.2( stud)-4.8(y of)-4.1( a m)9.6(i)]TJ 11.3892 0 TD .0017 Tc -.0002 Tw [(ddl)4.1(e-a)8.4(g)-1.3(ed)4.7( S)7(w)-.7(ed)4.7(i)4.1(s)1.6(h )6(po)4.7(p)4.7(u)-1.3(l)4.1(a)2.4(t)4.1(i)4.1(on.)6.2( )]TJ /TT16 1 Tf 12.5928 0 TD -.001 Tc .0025 Tw [(J Int Me)5.7(d)]TJ /TT10 1 Tf 3.8263 0 TD -.0028 Tc -.0017 Tw [( 2)-5.8(002)-5.8(; )-6(251)-5.8(:20)-5.8(7).2(-2)-5.8(16. )]TJ -30.6826 -1.1437 TD -.0015 Tc .003 Tw [( )-544.9(2)-4.5(1)1.5( )-646.7(Mallo)-4.5(n)-4.5( L, Broman)-4.5( JE, )6(Hetta )6(J. Is usag)-4.5(e of )6(hyp)-4.5(no)-4.5(tics asso)-4.5(ciated)-4.5( with m)9.9(o)-4.5(rtality)7.5(?)-18.7( )]TJ /TT16 1 Tf 34.6228 0 TD -.0004 Tc .0019 Tw [(Sleep M)6.3(e).3(d)]TJ /TT10 1 Tf 4.1856 0 TD -.003 Tc -.0015 Tw [( 2)-6(009)-6(; )-6(10\()-5.3(3\):2)-6(79)-6(-)]TJ -35.9341 -1.1497 TD .003 Tc 0 Tw [(28)6(6.)7.5( )]TJ -2.8743 -1.1497 TD .0021 Tc -.0006 Tw [( )-544.9(22)5.1( )-646.7(M)5(e)2.8(rl)4.5(o J)8(,).6( H)5.7(e)2.8(d)5.1(b)-.9(l)10.5(a)2.8(d B)4.4(,)6.6( O)5.7(g)-.9(re)8.8(n M)11(,).6( R)4.4(a)2.8(nst)4.5(a)2.8(m)13.5( J, O)5.7(s)2(t)4.5(e)2.8(r)17.7(g)5.1(ren)5.1( )]TJ 23.994 0 TD -.0001 Tc .0016 Tw [(PO, E)6(k)-3.1(eda)6.6(h)-3.1(l )59.9(A)51.4( et)8.3( al. )6(Inc)6.6(r)-2.4(ease)6.6(d)-3.1( ris)5.8(k)-3.1( )6(of ischaem)11.3(ic heart )]TJ -21.1198 -1.1437 TD -.0018 Tc .0033 Tw [(d)-4.8(i).6(sease m)9.6(o)-4.8(rtality in)-4.8( eld)-4.8(e)-1.1(rly men)-4.8( )6(u)-4.8(s)-1.9(ing)-4.8( anx)-4.8(i).6(o)-4.8(l)6.6(ytics-h)-4.8(y)1.2(p)-4.8(n)1.2(o)-4.8(tics and)-4.8( an)-4.8(alg)-4.8(e)-1.1(sics. )]TJ /TT16 1 Tf 10.02 0 0 10.02 407.4 167.5201 Tm -.0027 Tc .0042 Tw [(Eu)-5.7(r J Clin Pha)-5.7(r)-2.8(ma)-5.7(co)-5.7(l)]TJ /TT10 1 Tf 8.8443 0 TD -.0031 Tc -.0014 Tw [( 1)-6.1(996)-6.1(; )]TJ -39.4431 -1.1497 TD -.0034 Tc 0 Tw [(4)-6.4(9)-6.4(:)5(2)-6.4(61-)-5.7(265)-6.4(. )]TJ -2.8743 -1.1497 TD -.0012 Tc .0027 Tw [( )-544.9(2)-4.2(3)1.8( )-646.7(Ph)-4.2(illip)-4.2(s B, Man)-4.2(n)-4.2(i)7.2(n)-4.2(o)1.8( DM)7.7(. 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If each)-5( )6(p)-5(ill was )6(on)-5( )6(av)-5(erag)-5(e equ)-5(i).4(v)-5(a)4.7(len)-5(t).4( to)-5( )18(Th)-5(e )]TJ 22.1258 0 TD -.0017 Tc .0032 Tw [(In)-4.7(tern)-4.7(ation)-4.7(a)-1(l )6(Narco)-4.7(tics Con)-4.7(t).7(ro)-4.7(l Bo)-4.7(ard)49.9(s statistically-d)-4.7(efin)-4.7(ed)-4.7( )]TJ ET 1 g 70.5 639.48 471 11.52 re f 72 639.54 451.32 11.7 re f BT 10.02 0 0 10.02 72 641.8201 Tm 0 g .0019 Tc -.0004 Tw [(dai)4.3(l)4.3(y)4.9( do)4.9(se, at)4.3( t)10.3(h)-1.1(i)4.3(s)1.8( rat)4.3(e)2.6( )6(o)4.9(f)-.4( )6(hy)4.9(p)4.9(not)4.3(i)4.3(c)2.6( c)8.6(o)-1.1(n)4.9(s)1.8(um)13.3(pt)4.3(i)4.3(on )6(pe)8.6(r )6(hy)4.9(p)4.9(not)4.3(i)10.3(c)2.6( user)47.5(, i)4.3(t)4.3( w)5.5(o)4.9(ul)4.3(d)4.9( re)8.6(qui)4.3(re)8.6( 3)4.9(.).4(0)4.9(6)4.9(2)-1.1(5)4.9(%)2.6( *)4.9( \()5.6(3)-1.1(6)4.9(5)-1.1(.)6.4(2)4.9(5/)4.3(1)4.9(7)-1.1(7)4.9(.).4(4)4.9(9)4.9(\))-.4( = )]TJ ET 1 g 70.5 628.02 471 11.46 re f 72 628.02 449.04 11.7 re f BT 10.02 0 0 10.02 72 630.3 Tm 0 g .0015 Tc 0 Tw [(6.)6(3% )6(of)5.2( t)3.9(h)-1.5(e a)8.2(d)4.5(ul)3.9(t)3.9( p)4.5(o)-1.5(p)4.5(u)-1.5(l)3.9(a)2.2(t)3.9(i)3.9(o)4.5(n t)9.9(o)-1.5( c)8.2(o)-1.5(n)4.5(s)1.4(um)12.9(e t)3.9(h)-1.5(e )6(U.S)6.8(.)0( )6(defi)9.9(ned)4.5( d)4.5(a)2.2(i)3.9(l)3.9(y)4.5( dose c)8.2(o)4.5(ns)7.4(um)12.9(pt)3.9(i)3.9(on est)3.9(i)3.9(m)6.9(at)3.9(ed by)4.5( t)9.9(h)-1.5(e )6(Int)9.9(e)2.2(rnat)3.9(i)3.9(o)4.5(nal)3.9( )]TJ ET 1 g 70.5 616.5 471 11.52 re f 72 616.56 455.46 11.7 re f BT 10.02 0 0 10.02 72 618.84 Tm 0 g -.0019 Tc .0034 Tw [(N)-4.3(a)-1.2(r)-4.2(c)4.8(o)-4.9(tics Con)-4.9(t)6.5(r)-4.2(o)-4.9(l B)6.4(o)-4.9(ard)-4.9( )6(f)-4.2(o)1.1(r)-4.2( )6(20)-4.9(06-)-4.2(200)-4.9(8, th)-4.9(at )6(is, 6.3)-4.9(%)4.8( wou)-4.9(l).5(d b)-4.9(e)-1.2( )6(h)-4.9(ypno)-4.9(tic u)-4.9(s)4(er)-4.2(s. )6( Sin)-4.9(c)-1.2(e almo)-4.9(st )6(h)-4.9(a)-1.2(lf)-4.2( )6(o)-4.9(f)1.8( th)-4.9(e )6(zo)-4.9(lp)-4.9(id)-4.9(em)9.5( )]TJ ET 1 g 70.5 604.98 471 11.52 re f 72 605.04 466.02 11.7 re f BT 10.02 0 0 10.02 72 607.32 Tm 0 g -.0001 Tc .0016 Tw [(recipients )6(recei)8.3(ved 5-6.25 m)11.3(g)-3.1(. pills \(a)6.6(bo)]TJ 16.1018 0 TD -.0005 Tc -.004 Tw [(ut ha)6.2(lf )-6(of )-6(a statistica)-5.8(lly-define)6.2(d)-3.5( daily)]TJ 14.7126 0 TD 0 Tc .0015 Tw [( dose\), and )6(similar low )6(dose)6.7(s)-.1( m)11.4(a).7(y have )]TJ ET 1 g 70.5 593.52 471 11.46 re f 72 593.52 466.8 11.7 re f BT 10.02 0 0 10.02 72 595.8 Tm 0 g .0015 Tc 0 Tw [(been)4.5( p)4.5(r)-.8(esc)8.2(r)-.8(i)3.9(b)-1.5(e)8.2(d)-1.5( )6(wi)3.9(t)3.9(h)-1.5( s)7.4(o)-1.5(m)12.9(e)2.2( of)5.2( t)3.9(h)-1.5(e )6(ot)3.9(he)8.2(r c)8.2(o)-1.5(m)6.9(p)-1.5(o)4.5(u)4.5(nds)7.4(, i)3.9(t)3.9( m)12.9(i)3.9(ght)3.9( re)8.2(q)4.5(u)-1.5(i)3.9(r)-.8(e s)7.4(o)-1.5(m)6.9(e)2.2(what)3.9( m)12.9(o)-1.5(re t)9.9(h)4.5(an )6(6.)6(3% )6(of)5.2( ad)4.5(u)4.5(l)3.9(t)3.9(s)1.4( t)3.9(o)-1.5( eq)4.5(ual)3.9( t)3.9(h)-1.5(e)8.2( )]TJ ET 1 g 70.5 582 471 11.52 re f 72 582.06 452.28 11.7 re f BT 10.02 0 0 10.02 72 584.34 Tm 0 g .0017 Tc -.0002 Tw [(rep)4.7(o)-1.3(rt)4.1(e)8.4(d)-1.3( )6(20)4.7(0)4.7(6)-1.3(-)5.4(2)-1.3(0)4.7(0)4.7(8)-1.3( c)8.4(o)-1.3(n)4.7(s)1.6(um)13.1(pt)4.1(i)4.1(on )6(o)4.7(f)-.6( st)4.1(at)4.1(i)4.1(s)1.6(t)4.1(i)4.1(cal)4.1(l)4.1(y)4.7(-defi)4.1(n)-1.3(e)8.4(d)-1.3( )6(dai)4.1(l)4.1(y)4.7( dos)7.6(es. )6( M)4.6(o)4.7(re)8.4(ove)8.4(r)41.3(,).2( si)10.1(nce )6(hy)4.7(p)4.7(not)4.1(i)4.1(c)2.4( c)8.4(o)-1.3(n)4.7(s)1.6(um)13.1(pt)4.1(i)4.1(on )6(has)7.6( )]TJ ET 1 g 70.5 570.54 471 11.46 re f 72 570.54 432.36 11.7 re f BT 10.02 0 0 10.02 72 572.82 Tm 0 g .0003 Tc .0012 Tw [(increase)7(d)-2.7( si)8.7(nce)7( the a)7(v)]TJ 8.7305 0 TD -.003 Tc -.0015 Tw [(er)-5.3(ag)-6(e for)-5.3( 2)-6(006)-6(-2)-6(008)-6(,)]TJ 6.48 0 0 6.48 243.6 577.32 Tm 0 Tc 0 Tw (2 3)Tj 10.02 0 0 10.02 251.64 572.82 Tm -.0017 Tc .0032 Tw [( and)-4.7( co)-4.7(nsid)-4.7(eri)6.7(n)1.3(g)-4.7( th)-4.7(at t)6.7(h)-4.7(e )6(In)-4.7(tern)-4.7(atio)-4.7(n)-4.7(a)-1(l )6(Narcotics Co)-4.7(n)-4.7(t).7(ro)-4.7(l Board )]TJ ET 1 g 70.5 559.02 471 11.52 re f 72 559.08 449.34 11.7 re f BT 10.02 0 0 10.02 72 561.36 Tm 0 g .0015 Tc 0 Tw [(com)12.9(p)-1.5(i)3.9(l)3.9(a)2.2(t)3.9(i)3.9(on di)9.9(d )6(not)3.9( i)9.9(n)-1.5(cl)3.9(u)4.5(d)-1.5(e e)8.2(s)1.4(zo)4.5(pi)3.9(cl)3.9(one)8.2(, zal)9.9(epl)3.9(o)4.5(n, a)8.2(n)4.5(d a)8.2(n)-1.5(t)3.9(i)3.9(h)-1.5(i)3.9(s)1.4(t)3.9(a)2.2(m)6.9(i)3.9(nes w)5.1(h)-1.5(i)3.9(c)2.2(h )6(we c)8.2(o)-1.5(n)4.5(s)1.4(i)3.9(d)-1.5(er)5.2(ed )6(hy)4.5(p)4.5(not)3.9(i)3.9(c)2.2(s,)6( )6(we m)12.9(i)3.9(ght)3.9( )]TJ ET 1 g 70.5 547.5 471 11.52 re f 72 547.56 461.28 11.7 re f BT 10.02 0 0 10.02 72 549.84 Tm 0 g .0018 Tc -.0003 Tw [(ro)4.8(u)4.8(ghl)4.2(y)4.8( e)8.5(x)-1.2(t)4.2(r)-.5(ap)4.8(ol)4.2(at)4.2(e t)4.2(h)-1.2(at)4.2( )6(10%)8.5( )6(of)5.5( U.)6.3(S. a)8.5(d)4.8(ul)4.2(t)4.2(s)1.7( )6(m)7.2(i)4.2(ght)4.2( ha)8.5(ve c)8.5(o)4.8(nsum)13.2(ed )6(hy)4.8(p)4.8(not)10.2(i)4.2(c)2.5(s i)4.2(n)-1.2( )6(20)4.8(1)4.8(0)-1.2(. )6( )18(T)7.9(h)-1.2(i)4.2(s)1.7( i)4.2(s)1.7( a )6(ve)8.5(ry)4.8( r)5.5(o)4.8(ug)4.8(h e)8.5(s)1.7(t)4.2(i)-1.8(m)13.2(a)2.5(t)4.2(e)2.5( )]TJ ET 1 g 70.5 536.04 471 11.46 re f 72 536.04 431.88 11.7 re f BT 10.02 0 0 10.02 72 538.3201 Tm 0 g -.0022 Tc .0037 Tw [(w)-4.6(h)-5.2(ich)-5.2( )6(w)-4.6(o).8(u)-5.2(l).2(d no)-5.2(t in)-5.2(clud)-5.2(e )6(sed)-5.2(a)4.5(tiv)-5.2(e an)-5.2(tid)-5.2(ep)-5.2(r)-4.5(e)4.5(ssan)-5.2(ts su)-5.2(ch)-5.2( as t)6.2(r)1.5(azo)-5.2(don)-5.2(e )6(o)-5.2(r)1.5( low)-4.6(-)1.5(d)-5.2(o).8(se )6(d)-5.2(o).8(x)-5.2(e)4.5(p)-5.2(i).2(n)-5.2( )6(u)-5.2(s)-2.3(ed)-5.2( as )6(h)-5.2(ypno)-5.2(tics. )6( )]TJ ET 1 g 70.5 524.52 471 11.52 re f BT 10.02 0 0 10.02 72 526.86 Tm 0 g 0 Tc 0 Tw ( )Tj ET 1 g 70.5 513 471 11.52 re f 72 513.06 265.74 11.76 re f BT 10.02 0 0 10.02 72 515.22 Tm 0 g ( )Tj /TT12 1 Tf 3.5928 0 TD .0002 Tc .0013 Tw [(An es)6.1(timate )6(of h)5.5(y)-2.8(pn)5.5(otic-ass)6.1(ociated e)6.9(x)-2.8(cess)6.1( U.)4.7(S. )6(deaths)6.1(. )6( )]TJ ET 1 g 70.5 501.54 471 11.46 re f BT 10.02 0 0 10.02 72 503.7 Tm 0 g 0 Tc 0 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previ)8.9(ously )6(discussed, we)7.2( )]TJ 15.6826 0 TD .0001 Tc .0014 Tw [(ha)6.8(ve )6(no accurate est)8.5(i)-3.5(m)11.5(a).8(te of what )6(po)]TJ 14.7964 0 TD -.0046 Tw [(rtion of )-6(t)8.5(h)-2.9(e deaths)6( )-6(ass)6(o)-2.9(ciated with )]TJ ET 214.98 329.82 11.64 .47998 re f 229.14 329.82 18.9 .47998 re f 250.5 329.82 10.02 .47998 re f 263.04 329.82 33.3 .47998 re f 298.86 329.82 33.18 .47998 re f 334.56 329.82 8.4 .47998 re f 345.48 329.82 19.44 .47998 re f 367.38 329.82 28.92 .47998 re f 398.76 329.82 8.4 .47998 re f 409.68 329.82 12.18 .47998 re f 424.32 329.82 25.56 .47998 re f 452.4 329.82 41.1 .47998 re f 495.96 329.82 17.82 .47998 re f 1 g 70.5 317.52 471 11.52 re f 72 317.58 457.08 11.7 re f BT 10.02 0 0 10.02 72 319.86 Tm 0 g -.0018 Tc .0033 Tw [(h)-4.8(ypn)-4.8(o)-4.8(tics )6(p)-4.8(r)-4.1(escrip)-4.8(tion)-4.8(s)-1.9( are actu)-4.8(ally cau)-4.8(sed by th)-4.8(ese )6(h)-4.8(ypn)-4.8(o)-4.8(t).6(i)6.6(c)-1.1( )]TJ 24.6647 0 TD .0032 Tw [(dr)-4(ug)-4.7(s. )6(I)-4(n)1.3( 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Fc2*~}3xxqlSkՊ>W{VTGt-/[1u}UGvM]_hchOX?xwyx<]m6zWj|2R_*|G|,ݝLo$O eD<0c2,3鴛n8"_ьS~d;%Z12NMdv% vWKʖ]9dSӕL(}|>#::kޚ/`:e.^u^άzCi݆\Y3؛evHR.{g=rO ۢd$AFlI^2~LFNqWv%zu}\=GK{Nθ ԁ$*C%4*+YQDGmU~u!%JmQ Q?^a8v$ A~c뜱`xt-?~{cs$ ;qg#*lzWSHrSNlDgt>N`dmqK6kXYTLOfEIz]b*<-Mdm`(-MuTz͜4tt4jN4' t-p+܂+$KHᯀkddPpui`ֈ-[A.Ge̮lѶuR8Os+t&ANZkA};{VV'iyu/t?6~VOZٞ硝ZB2UϨY&UUFw,rzWLD15US _( endstream endobj 141 0 obj <>stream /GS1 gs BT /TT2 1 Tf 10.98 0 0 10.98 72 745.5601 Tm 0 g 0 Tc 0 Tw ( )Tj 20.8033 -60.9399 TD .0014 Tc (17 )Tj -20.8033 -2.3169 TD 0 Tc ( )Tj /TT14 1 Tf 12 0 0 12 243 708.84 Tm -.0001 Tc .0023 Tw (Additional Discussion )Tj /TT12 1 Tf 10.02 0 0 10.02 306 696.9 Tm 0 Tc 0 Tw ( )Tj /TT10 1 Tf -23.3533 -1.1497 TD .0015 Tc ( )Tj /TT12 1 Tf 3.5928 0 TD -.0012 Tc .0027 Tw [(Po)-4.2(ssibility of )6(g)-4.2(e)-.5(netic confo)-4.2(u)4.1(nding.)]TJ /TT10 1 Tf 14.5329 0 TD .0015 Tc 0 Tw [( )6( )]TJ -18.1257 -1.1317 TD 0 Tc ( )Tj 0 -1.1497 TD -.0019 Tc -.0026 Tw [( )-3347.3(Ep)-4.9(id)-4.9(em)9.5(io)-4.9(lo)-4.9(g)-4.9(i).5(c stu)-4.9(d)-4.9(i).5(es )-6(cann)-4.9(o)-4.9(t).5( to)-4.9(d)-4.9(a)-1.2(y )-6(co)-4.9(n)-4.9(t)6.5(ro)-4.9(l fo)-4.9(r )-6(g)-4.9(e)4.8(n)-4.9(e)]TJ 24.497 0 TD -.0016 Tc .0031 Tw [(tic suscep)-4.6(tib)-4.6(ility facto)-4.6(r)-3.9(s th)-4.6(at m)9.8(i).8(g)-4.6(h)-4.6(t).8( co)-4.6(n)-4.6(cei)6.8(v)-4.6(a)-.9(b)-4.6(l).8(y )6(bo)-4.6(th)-4.6( )]TJ -24.497 -1.1497 TD .001 Tc .0005 Tw [(i)3.4(n)-2(fl)3.4(ue)7.7(nce t)9.4(h)-2(e )6(n)4(eed )6(or)4.7( desi)9.4(re f)4.7(o)-2(r)4.7( hy)10(pn)4(ot)3.4(i)3.4(c)1.7(s a)7.7(n)-2(d)4( al)3.4(so)4( i)3.4(n)-2(fl)9.4(uen)4(ce su)4(rvi)9.4(v)-2(al)3.4(. 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-1.1437 TD [(di)4.1(ag)4.7(no)4.7(ses )6(pri)10.1(o)-1.3(r)5.4( t)4.1(o)-1.3( t)4.1(h)-1.3(e)8.4( pe)8.4(ri)4.1(o)4.7(d)-1.3(s )6(of)5.4( o)4.7(b)-1.3(se)8.4(rvat)4.1(i)4.1(o)4.7(n )6(\(Su)4.7(p)4.7(p)-1.3(l)4.1(e)2.4(m)13.1(e)2.4(nt)4.1(ary)4.7( )18(T)73.6(a)2.4(bl)4.1(e 4)4.7(\))-.6(. )6( J)7.6(u)4.7(dgi)10.1(ng)4.7( f)5.4(r)-.6(om)13.1( t)4.1(h)-1.3(e hi)4.1(g)4.7(h)-1.3(e)8.4(r)-.6( rat)4.1(e)2.4( )6(o)4.7(f)-.6( )6(num)13.1(ero)4.7(u)-1.3(s )]TJ 0 -1.1497 TD -.0003 Tw [(com)13.2(p)-1.2(l)4.2(i)4.2(cat)4.2(i)4.2(ons am)13.2(ong)4.8( t)4.2(h)-1.2(e )6(hy)4.8(p)4.8(not)4.2(i)4.2(c)2.5(s c)8.5(o)4.8(ho)4.8(rt)4.2( c)8.5(o)-1.2(m)13.2(p)-1.2(ared t)10.2(o)-1.2( c)8.5(o)4.8(nt)4.2(r)5.5(o)-1.2(l)4.2(s)1.7( be)8.5(f)5.5(o)-1.2(re t)10.2(h)4.8(e pe)8.5(ri)4.2(o)4.8(d)-1.2(s )6(of)5.5( o)4.8(b)4.8(s)1.7(ervat)4.2(i)4.2(o)4.8(n,)6.3( i)4.2(t)4.2( se)8.5(em)13.2(s pl)4.2(ausi)4.2(bl)4.2(e)8.5( )]TJ T* -.0004 Tc .0019 Tw [(that patients )6(who recei)8(ved hy)8.6(pnotics )6(had visited their )6(pr)]TJ 22.3413 0 TD -.0002 Tc .0017 Tw [(imary practitioners m)11.2(o)-3.2(re often )6(before the)6.5( pe)6.5(riods )6(of )]TJ -22.3413 -1.1437 TD -.0019 Tc .0034 Tw [(o)-4.9(b)-4.9(s)4(erv)-4.9(a)-1.2(tio)-4.9(n, con)-4.9(ceiv)-4.9(a)4.8(b)-4.9(l).5(y leav)-4.9(i)6.5(n)-4.9(g m)9.5(o)-4.9(re und)-4.9(iag)-4.9(n)1.1(o)-4.9(s)-2(ed)-4.9( )6(h)-4.9(y)1.1(p)-4.9(e)4.8(rten)-4.9(sion)-4.9( still to)-4.9( )6(b)-4.9(e)4.8( first-d)-4.9(i).5(agno)-4.9(sed)-4.9( am)9.5(o)-4.9(n)-4.9(g)1.1( con)-4.9(t).5(ro)-4.9(ls. )]TJ 0 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1557 TD ( )Tj /TT12 1 Tf 3.5928 0 TD -.0042 Tc .0057 Tw [(H)-4.8(e)-3.5(a)-7.2(r)2.5(t)-6.5( fa)-7.2(ilu)-4.9(r)14.5(e)-3.5( )6(h)-4.9(a)-7.2(za)-7.2(r)-3.5(d)-4.9( rat)-6.5(i)-1.8(o)-7.2(s)-4.3(.)]TJ /TT10 1 Tf 11.7365 0 TD .0015 Tc 0 Tw [( )6( )]TJ -15.3293 -1.1377 TD 0 Tc ( )Tj 0 -1.1497 TD -.0012 Tc .0027 Tw [( )-3341.3(Of )6(co)-4.2(m)10.2(o)-4.2(rb)-4.2(i)7.2(d)-4.2(ities, ap)-4.2(art )6(fro)-4.2(m)10.2( 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24.5569 0 TD 0 Tc .0015 Tw [(es in both gende)6.7(rs a)6.7(ssociat)]TJ 10.6407 0 TD .0015 Tc -.006 Tw [(ed wi)3.9(t)3.9(h)-1.5( hy)4.5(p)4.5(not)9.9(i)3.9(c)2.2( )-6(use,)6( )-6(an)4.5(d )]TJ ET 1 g 70.5 211.74 471 11.52 re f BT 10.02 0 0 10.02 72 214.08 Tm 0 g -.0001 Tw [(m)13(o)-1.4(rt)4(al)4(it)4(y)4.6( was )6(hi)4(g)4.6(h)-1.4(er)5.3( am)13(ong )6(m)7(e)2.3(n usi)10(n)-1.4(g)4.6( hy)10.6(p)4.6(not)4(i)4(c)2.3(s.)]TJ 6.48 0 0 6.48 272.28 218.58 Tm 0 Tc 0 Tw (24)Tj 10.02 0 0 10.02 278.76 214.08 Tm -.0015 Tc .003 Tw [( )6( It is i)6.9(n)-4.5(teresting)-4.5( t)6.9(h)-4.5(at )6(in)-4.5( th)-4.5(e curren)-4.5(t).9( )6(data set, u)-4.5(s)-1.6(e of )6(h)-4.5(ypn)-4.5(o)-4.5(tics )]TJ ET 1 g 70.5 200.22 471 11.52 re f BT 10.02 0 0 10.02 72 202.56 Tm 0 g .0018 Tc -.0003 Tw [(pr)5.5(o)4.8(v)-1.2(i)4.2(d)-1.2(e)8.5(d)-1.2( )6(no)4.8( p)4.8(r)5.5(ot)4.2(ect)4.2(i)4.2(on )6(w)5.4(h)-1.2(at)4.2(s)7.7(o)-1.2(eve)8.5(r)-.5( a)8.5(g)-1.2(ai)4.2(nst)4.2( )6(d)4.8(e)2.5(vel)4.2(o)4.8(pm)13.2(ent)4.2( of )6(obe)8.5(si)4.2(t)4.2(y)4.8( \(Su)4.8(p)4.8(p)-1.2(l)4.2(e)-3.5(m)13.2(e)2.5(nt)4.2(ary)4.8( )18(T)73.7(a)2.5(bl)10.2(e 4 a)8.5(n)4.8(d S)7.1(u)4.8(ppl)4.2(e)8.5(m)7.2(ent)4.2(a)2.5(ry)4.8( )]TJ ET 1 g 70.5 188.76 471 11.46 re f BT 10.02 0 0 10.02 72 191.0401 Tm 0 g -.0719 Tc .0734 Tw [(Ta)-71.2(b)-74.9(l)-69.5(e)-71.2( 6)-68.9(\))-74.2(.)-67.4( )]TJ ET 1 g 70.5 177.24 471 11.52 re f BT 10.02 0 0 10.02 72 179.58 Tm 0 g 0 Tc 0 Tw ( )Tj ET 1 g 70.5 165.72 471 11.52 re f 72 165.78 455.16 11.76 re f BT /TT12 1 Tf 10.02 0 0 10.02 72 167.94 Tm 0 g -.0006 Tc .0021 Tw [( )-3341.3(Com)6.1(b)-1.3(ining the extrapol)7.8(ated Geis)]TJ 17.7066 0 TD .001 Tc .0005 Tw [(i)3.4(n).3(ger)25.7( a)4(n)6.3(d In)6.3(tern)6.3(ati)9.4(o)-2(n)6.3(a)-2(l)3.4( N)4.6(a)-2(r)19.7(c)7.7(oti)3.4(c)1.7(s )6(C)4.6(o)-2(nt)4.7(r)19.7(o)-2(l)3.4( B)9.3(oar)7.7(d )6(dat)4.7(a)-2( )6(t)4.7(o)-2( es)6.9(ti)3.4(ma)4(te )]TJ ET 1 g 70.5 154.26 471 11.46 re f 72 154.26 252.78 11.76 re f BT 10.02 0 0 10.02 72 156.42 Tm 0 g 0 Tc .0015 Tw [( )-3341.3(the p)5.3(e).7(r)18.7(centage of )6(U.S.)4.5( adults con)5.3(s)-.1(umin)5.3(g h)5.3(y)-3(pn)5.3(otics)5.9(.)4.5( )]TJ ET 1 g 70.5 142.74 471 11.52 re f BT 10.02 0 0 10.02 306 144.9601 Tm 0 g 0 Tw ( )Tj ET 1 g 70.5 131.22 471 11.52 re f 72 131.28 443.82 11.7 re f BT 10.02 0 0 10.02 72 133.5601 Tm 0 g ( )Tj /TT10 1 Tf 3.5928 0 TD -.0022 Tc .0037 Tw [(A)-4.6(s)-2.3( ex)-5.2(p)-5.2(l).2(ai)6.2(n)-5.2(e)-1.5(d at th)-5.2(e b)-5.2(e)4.5(g)-5.2(i).2(nn)-5.2(i)6.2(n)-5.2(g of)-4.5( th)-5.2(is )6(Supp)-5.2(lemen)-5.2(t).2(, fo)-5.2(r)-4.5( )6(20)-5.2(06-)-4.5(200)-5.2(8, )18(Th)-5.2(e )6(I)-4.5(n)-5.2(t)6.2(e)-1.5(r)-4.5(n)-5.2(ation)-5.2(a)-1.5(l )6(N)-4.6(a)-1.5(rco)-5.2(tics Con)-5.2(t).2(ro)-5.2(l )]TJ ET 1 g 70.5 119.76 471 11.46 re f 72 119.76 458.52 11.7 re f BT 10.02 0 0 10.02 72 122.04 Tm 0 g .0015 Tc 0 Tw [(B)3.8(o)-1.5(ar)5.2(d est)3.9(i)3.9(m)12.9(at)3.9(ed t)3.9(h)-1.5(at)3.9( t)9.9(h)-1.5(e )6(U.S)6.8(.)0( )6(con)4.5(s)1.4(um)12.9(ed 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0 0 m 0 1.38 -1.14 2.46 -2.52 2.46 c -3.9 2.46 -4.98 1.38 -4.98 0 c -4.98 -1.38 -3.9 -2.52 -2.52 -2.52 c -1.14 -2.52 0 -1.38 0 0 c s Q BT /TT14 1 Tf 18.7781 0 0 18.7781 192.96 692.52 Tm 0 g .0005 Tc .0172 Tw [(HY)12.5(P)9.3(N).6(O)24.3(T)-43.7(I)13.1(C).6( US)-19.5(E)-22.7( an)-11.7(d)-11.7( A)32.5(G)-7.7(E)-22.7(:)]TJ -1.9235 -1.1822 TD -.0001 Tc .0181 Tw [(E)-23.3(F)-12.3(F)-15.5(E)-20.1(CT)-47.5(S)-23.3( o)19.6(n)-12.3( CA)31.9(NCE)-20.1(R I)15.7(NCI)15.7(DE)-23.3(NCE)]TJ ET 0 G 1.846 w q 1 0 0 1 133.56 413.4 cm 0 0 m 369.78 0 l S 1 0 0 1 0 0 cm 0 0 m 0 -3.6 l S Q BT 11.903 0 0 11.903 130.14 397.5 Tm 0 Tc 0 Tw (0)Tj ET q 1 0 0 1 145.8 413.4 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -3.6 l S Q BT 11.903 0 0 11.903 204 397.5 Tm (1)Tj ET q 1 0 0 1 219.66 413.4 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.42 0 cm 0 0 m 0 -3.6 l S Q BT 11.903 0 0 11.903 277.98 397.5 Tm (2)Tj ET q 1 0 0 1 293.64 413.4 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.42 0 cm 0 0 m 0 -3.6 l S Q BT 11.903 0 0 11.903 351.96 397.5 Tm (3)Tj ET q 1 0 0 1 367.62 413.4 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.42 0 cm 0 0 m 0 -3.6 l S Q BT 11.903 0 0 11.903 425.94 397.5 Tm (4)Tj ET q 1 0 0 1 441.6 413.4 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.36 0 cm 0 0 m 0 -2.04 l S 1 0 0 1 12.3 0 cm 0 0 m 0 -3.6 l S Q BT 11.903 0 0 11.903 499.7999 397.5 Tm (5)Tj ET q 1 0 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0 9.84 cm 0 0 m -2.04 0 l S 1 0 0 1 0 9.84 cm 0 0 m -3.6 0 l S Q BT 11.903 0 0 11.903 105.3 606.12 Tm [(0.)29.2(95)]TJ ET q 1 0 0 1 133.56 620.28 cm 0 0 m -2.04 0 l S 1 0 0 1 0 9.84 cm 0 0 m -2.04 0 l S 1 0 0 1 0 9.84 cm 0 0 m -2.04 0 l S 1 0 0 1 0 9.84 cm 0 0 m -2.04 0 l S 1 0 0 1 0 9.84 cm 0 0 m -3.6 0 l S Q BT 11.903 0 0 11.903 105.3 655.38 Tm [(1.)29.2(00)]TJ 4.7988 -11.6945 TD .0121 Tc -.0278 Tw [(age 18-)37.6(55:)-17.8( no hypnot)37.6(i)27.8(c)-1.4( )5.1(N)58.8(=)26.5(13039)]TJ ET q 141.84 519.42 6.66 2.1 re W n 0 .445 .699 RG q 1 0 0 1 141.84 520.5 cm 0 0 m 5.58 0 l S Q Q 0 .445 .699 RG q 1 0 0 1 151.14 520.5 cm 0 0 m 5.52 0 l S Q q 159.36 519.42 .59999 2.1 re W n q 1 0 0 1 160.38 520.5 cm 0 0 m 5.52 0 l S Q Q BT 11.903 0 0 11.903 162.42 502.02 Tm [(age 55-)37.5(65:)-17.9( no hypnot)37.5(i)27.7(c)-1.5( )5.1(N)58.7(=)26.4(4049)]TJ ET q 141.84 505.26 18.12 2.1 re W n q 1 0 0 1 141.84 506.34 cm 0 0 m 120.84 0 l S Q Q BT 11.903 0 0 11.903 162.42 487.86 Tm [(age 65-)37.5(75:)-17.9( 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m 1.86 0 l S Q BT 11.903 0 0 11.903 162.42 444.78 Tm [(age 50-)37.6(65:)-17.8( had hypnot)32.6(i)32.9(c)-1.4( )5.1(N)58.8(=)26.5(1758)]TJ ET q 141.84 447.72 18.12 2.7 re W n 2.461 w q 1 0 0 1 141.84 449.1 cm 0 0 m 120.84 0 l S Q Q BT 11.903 0 0 11.903 162.42 430.62 Tm [(age 65-)37.6(75:)-17.8( had hypnot)32.6(i)32.9(c)-1.4( )5.1(N)58.8(=)26.5(1477)]TJ ET q 141.84 433.86 18.12 2.1 re W n q 1 0 0 1 141.84 434.94 cm 0 0 m 120.84 0 l S Q Q .836 .367 .5 rg .836 .367 .5 RG .103 w q 1 0 0 1 148.44 437.4 cm 0 0 m 4.92 0 l 2.46 -4.92 l b* Q BT 11.903 0 0 11.903 162.42 417.06 Tm 0 g .0124 Tc -.0332 Tw [(age )-5.1(>)26.8(75:)-17.5( had hypnot)32.9(i)33.2(c)-1.1( )-5.1(N)64.1(=)26.8(1489)]TJ ET q 141.84 420.3 18.12 2.1 re W n .836 .367 0 RG 1.846 w q 1 0 0 1 141.84 421.38 cm 0 0 m 120.84 0 l S Q Q .402 .184 0 RG 1.23 w q 1 0 0 1 153.42 421.38 cm 0 0 m 0 1.38 -1.14 2.46 -2.52 2.46 c -3.9 2.46 -4.98 1.38 -4.98 0 c -4.98 -1.38 -3.9 -2.52 -2.52 -2.52 c -1.14 -2.52 0 -1.38 0 0 c s Q BT 17.0337 0 0 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u)-6.8(s)-2.8(ed como)]TJ 26.3008 0 TD [(rbidit)-6.8(y)12.4( )-7.5(groups as covariates. 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[(rat)8(e).3(d in Supplementary Fi)8(gure )6(2. )]TJ 13.6467 0 TD -.0002 Tc .0017 Tw [(The t)8.2(o)-3.2(p 10%)6.5( of )6(participa)6.5(n)-3.2(ts receive)6.5(d )]TJ -30.6168 -1.1497 TD -.0001 Tc .0016 Tw [(64.9% )6(of t)8.3(h)-3.1(e )6(prescri)8.3(p)-3.1(tion dos)5.8(e).6(s and a)6.6(v)]TJ 15.497 0 TD -.0016 Tc .0031 Tw [(erag)-4.6(ed)-4.6( )6(1)37.3(1)37.3(1)31.3(1 to)-4.6(tal doses p)-4.6(e)5.1(r year)50(. )6( )18(Th)-4.6(e )6(d)-4.6(i).8(stribu)-4.6(tion)-4.6( )6(was )6(q)-4.6(u)-4.6(ite sim)9.8(i).8(l)-5.2(a)-.9(r for )]TJ -15.497 -1.1497 TD -.0017 Tc [(zo)-4.7(lp)-4.7(id)-4.7(em)9.7(, with th)-4.7(e top)-4.7( )6(10)-4.7(% )6(receiv)-4.7(i).7(n)-4.7(g)1.3( 62)-4.7(% of th)-4.7(e )6(p)-4.7(r)-4(escrip)-4.7(tion)-4.7(s)]TJ 25.0599 0 TD -.0023 Tc .0038 Tw [( and)-5.3( av)-5.3(erag)-5.3(in)-5.3(g 886)-5.3( )6(p)-5.3(ills \(eith)-5.3(er )6(5)-5.3( )6(o)-5.3(r)1.4( 10)-5.3( m)9.1(g)-5.3(.\) )6(p)-5.3(e)-1.6(r year)49.3(. )]TJ -25.0599 -1.1437 TD 0 Tc 0 Tw ( )Tj ET endstream endobj 180 0 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612 -792 re W n .992 .914 .852 rg 263.76 558 35.52 11.52 re f Q .992 .914 .852 rg 268.62 558 25.2 11.52 re f BT /TT10 1 Tf 10.02 0 0 10.02 268.62 560.34 Tm 0 g .003 Tc 0 Tw [(0.)7.5(00)6(0)6( )]TJ ET q 304.62 569.52 -5.34 -11.52 re 299.28 569.52 m h 416.28 569.52 -5.46 -11.52 re 410.82 569.52 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 299.28 558 117 11.52 re f Q .992 .914 .852 rg 304.62 558 106.2 11.52 re f BT 10.02 0 0 10.02 321.42 560.34 Tm 0 g -.0022 Tc .0037 Tw [(6)-5.2(0).8(.40)-5.2( )6(\(3)-5.2(6.98)-5.2( t)6.2(o).8( 98)-5.2(.6)-5.2(5\) )]TJ ET q 421.62 569.52 -4.86 -11.52 re 416.76 569.52 m h 505.74 569.52 -4.92 -11.52 re 500.82 569.52 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 416.76 558 88.98 11.52 re f Q .992 .914 .852 rg q 1 0 0 1 421.62 569.52 cm 0 0 m 79.2 0 l 79.2 -11.52 l 0 -11.52 l f Q BT 10.02 0 0 10.02 483.3 560.34 Tm 0 g .003 Tc 0 Tw [(4.)7.5(08)]TJ ET 262.8 558 .96002 11.52 re f 415.8 558 .95999 11.52 re f 505.8 558 .96002 11.52 re f BT /TT12 1 Tf 10.02 0 0 10.02 184.44 548.7 Tm 9.4087 Tc [( )5886.2( )5413.2( )5802.4( )3568.9( )]TJ ET 262.8 546.54 .96002 11.46 re f 415.8 546.54 .95999 11.46 re f 505.8 546.54 .96002 11.46 re f BT 10.02 0 0 10.02 184.44 537.2401 Tm -.0037 Tc 12.8375 Tw [( C)-6.1(ANC)-6.1(ER)-6.1(S )3371.2( )]TJ ET 262.8 535.02 .96002 11.52 re f 415.8 535.02 .95999 11.52 re f 505.8 535.02 .96002 11.52 re f BT 10.02 0 0 10.02 166.38 519.96 Tm .0015 Tc 0 Tw [(GRO)6.9(U)-.9(P)7.5( )]TJ 11.1497 .5749 TD 0 Tc ( )Tj -.3054 -1.1497 TD .0006 Tc .0009 Tw [(P )-3766.5(AGE )6(HR)4.2( \()4.3(9)3.6(5)3.6(%)12.6( C.I.\))4.3( )]TJ 18.5808 1.1497 TD .0015 Tc 0 Tw ( )Tj -2.8443 -1.1497 TD .0002 Tc .0013 Tw [(Hyp)5.5(n)-.5(otic H)5.6(R)3.8( )]TJ ET 262.8 512.04 .96002 22.98 re f 415.8 512.04 .95999 22.98 re f 505.8 512.04 .96002 22.98 re f BT 10.02 0 0 10.02 111.12 501.72 Tm -.0025 Tc .004 Tw [(a)-5.5(g)-5.5(e)4.2( 18-)-4.8(55)-5.5(, no)-5.5( )6(hy)-5.5(pnot)-4.8(ics, )6(N)-4.9(=)4.5(1)-5.5(303)-5.5(9 )]TJ /TT10 1 Tf 17.9701 .012 TD -.0013 Tc .0028 Tw [(REFERENCE:)7.1( HR=1)-4.3(.0 )]TJ ET 105.78 511.08 157.02 .96002 re f 262.8 511.02 .96002 1.02 re f 263.76 511.08 152.04 .96002 re f 415.8 511.02 .95999 1.02 re f 416.76 511.08 89.04 .96002 re f 505.8 511.02 .96002 1.02 re f 262.8 499.5 .96002 11.52 re f 415.8 499.5 .95999 11.52 re f 505.8 499.5 .96002 11.52 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 490.2 Tm -.0025 Tc .004 Tw [(a)-5.5(g)-5.5(e)4.2( 55-)-4.8(65)-5.5(, no)-5.5( )6(hy)-5.5(pnot)-4.8(ics, )6(N)-4.9(=)4.5(4)-5.5(049 )]TJ /TT10 1 Tf 15.988 .012 TD .0028 Tc -.0013 Tw [(0.)7.3(00)5.8(0)5.8( )-4035.9(2.)7.3(55)5.8( \()6.5(2)-.2(.)7.3(1)41.7(1 t)5.2(o)5.8( 3)5.8(.)7.3(08)5.8(\))6.5( )-4778.4( )]TJ ET 262.8 488.04 .96002 11.46 re f 415.8 488.04 .95999 11.46 re f 505.8 488.04 .96002 11.46 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 478.7401 Tm -.0025 Tc .004 Tw [(a)-5.5(g)-5.5(e)4.2( 65-)-4.8(75)-5.5(, no)-5.5( )6(hy)-5.5(pnot)-4.8(ics, )6(N)-4.9(=)4.5(3)-5.5(641 )]TJ /TT10 1 Tf 15.988 .012 TD .0028 Tc -.0013 Tw [(0.)7.3(00)5.8(0)5.8( )-4000(4.)7.3(78)5.8( \()6.5(4)-.2(.)7.3(0)5.8(3 t)5.2(o)5.8( 5)5.8(.)7.3(67)5.8(\))6.5( )-4778.4( )]TJ ET 262.8 476.52 .96002 11.52 re f 415.8 476.52 .95999 11.52 re f 505.8 476.52 .96002 11.52 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 467.22 Tm -.0023 Tc -.0022 Tw [(a)-5.3(g)-5.3(e)-1.6(>75)-5.3(,)-3.8( )-6( )-6( )-6(no)-5.3( hy)-5.3(pnot)-4.6(ics, N)-4.7(=)4.6(2)-5.3(945 )]TJ /TT10 1 Tf 15.988 .012 TD .0028 Tc -.0013 Tw [(0.)7.3(00)5.8(0)5.8( )-4000(5.)7.3(73)5.8( \()6.5(4)-.2(.)7.3(7)5.8(7 t)5.2(o)5.8( 6)5.8(.)7.3(90)5.8(\))6.5( )-4778.4( )]TJ ET 262.8 465 .96002 11.52 re f 415.8 465 .95999 11.52 re f 505.8 465 .96002 11.52 re f q 111.12 465 -5.34 -11.46 re 105.78 465 m h 263.28 465 -5.46 -11.46 re 257.82 465 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 105.78 453.54 157.5 11.46 re f Q .992 .914 .852 rg 111.12 453.54 146.7 11.46 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 455.7 Tm 0 g -.0031 Tc .0046 Tw [(a)-6.1(g)-6.1(e)3.6( 18-)-5.4(55)-6.1(, ha)-6.1(d hypno)-6.1(t)-5.4(ic, N)-5.5(=)3.9(5)-6.1(807 )]TJ ET q 268.62 465 -4.86 -11.46 re 263.76 465 m h 299.28 465 -5.46 -11.46 re 293.82 465 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 263.76 453.54 35.52 11.46 re f Q .992 .914 .852 rg 268.62 453.54 25.2 11.46 re f BT /TT10 1 Tf 10.02 0 0 10.02 271.32 455.82 Tm 0 g .003 Tc 0 Tw [(0.)7.5(19)6(8)6( )]TJ ET q 304.62 465 -5.34 -11.46 re 299.28 465 m h 416.28 465 -5.46 -11.46 re 410.82 465 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 299.28 453.54 117 11.46 re f Q .992 .914 .852 rg 304.62 453.54 106.2 11.46 re f BT 10.02 0 0 10.02 336.42 455.82 Tm 0 g .0027 Tc -.0012 Tw [(1.)7.2(16)5.7( \()6.4(0)-.3(.)7.2(9)5.7(3 t)5.1(o)5.7( 1)5.7(.)7.2(44)5.7(\))6.4( )]TJ ET q 421.62 465 -4.86 -11.46 re 416.76 465 m h 505.74 465 -4.92 -11.46 re 500.82 465 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 416.76 453.54 88.98 11.46 re f Q .992 .914 .852 rg q 1 0 0 1 421.62 465 cm 0 0 m 79.2 0 l 79.2 -11.46 l 0 -11.46 l f Q BT 10.02 0 0 10.02 483.3 455.82 Tm 0 g .003 Tc 0 Tw [(1.)7.5(16)]TJ ET 262.8 453.54 .96002 11.46 re f 415.8 453.54 .95999 11.46 re f 505.8 453.54 .96002 11.46 re f q 111.12 453.54 -5.34 -11.52 re 105.78 453.54 m h 263.28 453.54 -5.46 -11.52 re 257.82 453.54 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 105.78 442.02 157.5 11.52 re f Q .992 .914 .852 rg 111.12 442.02 146.7 11.52 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 444.24 Tm 0 g -.0027 Tc .0042 Tw [(a)-5.7(g)-5.7(e)4( 55-)-5(65)-5.7(, ha)-5.7(d hypno)-5.7(t)-5(ics, N=1)-5.7(758 )]TJ ET q 268.62 453.54 -4.86 -11.52 re 263.76 453.54 m h 299.28 453.54 -5.46 -11.52 re 293.82 453.54 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 263.76 442.02 35.52 11.52 re f Q .992 .914 .852 rg 268.62 442.02 25.2 11.52 re f BT /TT10 1 Tf 10.02 0 0 10.02 271.32 444.36 Tm 0 g .003 Tc 0 Tw [(0.)7.5(00)6(0)6( )]TJ ET q 304.62 453.54 -5.34 -11.52 re 299.28 453.54 m h 416.28 453.54 -5.46 -11.52 re 410.82 453.54 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 299.28 442.02 117 11.52 re f Q .992 .914 .852 rg 304.62 442.02 106.2 11.52 re f BT 10.02 0 0 10.02 336.42 444.36 Tm 0 g .0027 Tc -.0012 Tw [(3.)7.2(05)5.7( \()6.4(2)-.3(.)7.2(4)5.7(2 t)5.1(o)5.7( 3)5.7(.)7.2(84)5.7(\))6.4( )]TJ ET q 421.62 453.54 -4.86 -11.52 re 416.76 453.54 m h 505.74 453.54 -4.92 -11.52 re 500.82 453.54 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 416.76 442.02 88.98 11.52 re f Q .992 .914 .852 rg q 1 0 0 1 421.62 453.54 cm 0 0 m 79.2 0 l 79.2 -11.52 l 0 -11.52 l f Q BT 10.02 0 0 10.02 483.3 444.36 Tm 0 g .003 Tc 0 Tw [(1.)7.5(25)]TJ ET 262.8 442.02 .96002 11.52 re f 415.8 442.02 .95999 11.52 re f 505.8 442.02 .96002 11.52 re f q 111.12 442.02 -5.34 -11.52 re 105.78 442.02 m h 263.28 442.02 -5.46 -11.52 re 257.82 442.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 105.78 430.5 157.5 11.52 re f Q .992 .914 .852 rg 111.12 430.5 146.7 11.52 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 432.72 Tm 0 g -.0027 Tc .0042 Tw [(a)-5.7(g)-5.7(e)4( 65-)-5(75)-5.7(, ha)-5.7(d hypno)-5.7(t)-5(ics, N=1)-5.7(477 )]TJ ET q 268.62 442.02 -4.86 -11.52 re 263.76 442.02 m h 299.28 442.02 -5.46 -11.52 re 293.82 442.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 263.76 430.5 35.52 11.52 re f Q .992 .914 .852 rg 268.62 430.5 25.2 11.52 re f BT /TT10 1 Tf 10.02 0 0 10.02 271.32 432.84 Tm 0 g .003 Tc 0 Tw [(0.)7.5(00)6(0)6( )]TJ ET q 304.62 442.02 -5.34 -11.52 re 299.28 442.02 m h 416.28 442.02 -5.46 -11.52 re 410.82 442.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 299.28 430.5 117 11.52 re f Q .992 .914 .852 rg 304.62 430.5 106.2 11.52 re f BT 10.02 0 0 10.02 336.42 432.84 Tm 0 g .0027 Tc -.0012 Tw [(5.)7.2(53)5.7( \()6.4(4)-.3(.)7.2(5)5.7(1 t)5.1(o)5.7( 6)5.7(.)7.2(79)5.7(\))6.4( )]TJ ET q 421.62 442.02 -4.86 -11.52 re 416.76 442.02 m h 505.74 442.02 -4.92 -11.52 re 500.82 442.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 416.76 430.5 88.98 11.52 re f Q .992 .914 .852 rg q 1 0 0 1 421.62 442.02 cm 0 0 m 79.2 0 l 79.2 -11.52 l 0 -11.52 l f Q BT 10.02 0 0 10.02 483.3 432.84 Tm 0 g .003 Tc 0 Tw [(1.)7.5(20)]TJ ET 262.8 430.5 .96002 11.52 re f 415.8 430.5 .95999 11.52 re f 505.8 430.5 .96002 11.52 re f q 111.12 430.5 -5.34 -11.46 re 105.78 430.5 m h 263.28 430.5 -5.46 -11.46 re 257.82 430.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 105.78 419.04 157.5 11.46 re f Q .992 .914 .852 rg 111.12 419.04 146.7 11.46 re f BT /TT12 1 Tf 10.02 0 0 10.02 111.12 421.2 Tm 0 g -.002 Tc .0035 Tw [(a)-5(g)-5(e)4.7( >75)-5(,)2.5( )6( ha)-5(d hypno)-5(t)-4.3(ics, N=1)-5(489 )]TJ ET q 268.62 430.5 -4.86 -11.46 re 263.76 430.5 m h 299.28 430.5 -5.46 -11.46 re 293.82 430.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 263.76 419.04 35.52 11.46 re f Q .992 .914 .852 rg 268.62 419.04 25.2 11.46 re f BT /TT10 1 Tf 10.02 0 0 10.02 271.32 421.32 Tm 0 g .003 Tc 0 Tw [(0.)7.5(00)6(0)6( )]TJ ET q 304.62 430.5 -5.34 -11.46 re 299.28 430.5 m h 416.28 430.5 -5.46 -11.46 re 410.82 430.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 299.28 419.04 117 11.46 re f Q .992 .914 .852 rg 304.62 419.04 106.2 11.46 re f BT 10.02 0 0 10.02 336.42 421.32 Tm 0 g .0027 Tc -.0012 Tw [(6.)7.2(85)5.7( \()6.4(5)-.3(.)7.2(5)5.7(7 t)5.1(o)5.7( 8)5.7(.)7.2(44)5.7(\))6.4( )]TJ ET q 421.62 430.5 -4.86 -11.46 re 416.76 430.5 m h 505.74 430.5 -4.92 -11.46 re 500.82 430.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 416.76 419.04 88.98 11.46 re f Q .992 .914 .852 rg q 1 0 0 1 421.62 430.5 cm 0 0 m 79.2 0 l 79.2 -11.46 l 0 -11.46 l f Q BT 10.02 0 0 10.02 483.3 421.32 Tm 0 g .003 Tc 0 Tw [(1.)7.5(22)]TJ ET 262.8 419.04 .96002 11.46 re f 415.8 419.04 .95999 11.46 re f 505.8 419.04 .96002 11.46 re f BT 10.02 0 0 10.02 72 409.86 Tm 0 Tc ( )Tj /TT12 1 Tf 0 -1.1617 TD ( )Tj 1.5329 -1.1497 TD -.0005 Tc .002 Tw [(Supplemen)4.8(tar)6.2(y)-3.5( )18(T)97.6(a)-3.5(ble )6(1)56.4(1)-3.5(: H)4.9(a)-3.5(z)6.2(a)-3.5(rd )6(Ratios)5.4( for)18.2( H)4.9(y)-3.5(p)4.8(n)-1.2(otic )]TJ 23.2695 0 TD -.0001 Tc .0016 Tw [(Users )59.9(Associ)8.3(ate)6.6(d)-.8( with S)5.2(p)-.8(ecifi)8.3(c Inciden)5.2(t)-2.4( )6(Cancers)5.8( )]TJ -24.8024 -1.1437 TD 0 Tc 0 Tw ( )Tj 0 -1.1377 TD .0015 Tc [( )6( )6( )]TJ /TT10 1 Tf 2.2515 0 TD -.0015 Tc .003 Tw [(T)76.4(o)-4.5( furth)-4.5(e)5.2(r ex)-4.5(p)-4.5(l)6.9(o)-4.5(r)-3.8(e t)6.9(h)-4.5(e )6(po)-4.5(ssib)-4.5(ility th)-4.5(at )6(h)-4.5(ypn)-4.5(o)-4.5(tics m)9.9(a)]TJ 20.4551 0 TD -.0014 Tc .0029 Tw [(y in)-4.4(crease )6(h)-4.4(azard)-4.4(s )6(o)-4.4(f)2.3( m)10(a)-.7(j)-5(o)-4.4(r can)-4.4(cer)38.2(, we p)-4.4(e)5.3(rfo)-4.4(r)2.3(med)-4.4( )]TJ -22.7066 -1.1437 TD .0014 Tc .0001 Tw [(expl)9.8(orat)9.8(ory)4.4( a)8.1(n)4.4(al)3.8(y)4.4(s)1.3(es fo)4.4(r t)3.8(h)-1.6(e)8.1( a)8.1(ssoci)3.8(at)3.8(i)3.8(o)-1.6(n)4.4( o)4.4(f)-.9( a)8.1(n)-1.6(y)4.4( hy)10.4(pn)4.4(ot)3.8(i)3.8(c)2.1( p)4.4(r)]TJ 23.3892 0 TD -.0012 Tc .0027 Tw [(escrip)-4.2(tion)-4.2( )6(with th)-4.2(e in)-4.2(ci)7.2(d)-4.2(e)5.5(n)-4.2(ce )6(o)-4.2(f)]TJ 12.5808 0 TD -.0002 Tc .0017 Tw [( 10 s)5.7(p)-3.2(ecific c)6.5(a).5(tegories of )]TJ -35.9701 -1.1497 TD -.0014 Tc -.0031 Tw [(maj)-5(o)-4.4(r )-6(can)-4.4(cers \(Supp)-4.4(lem)10(e)-.7(n)-4.4(t)1(ary )12(T)70.5(a)-.7(b)-4.4(l)1(e )-6(1)37.5(1)-4.4(.\) In ad)-4.4(d)-4.4(ition)-4.4(,)-2.9( HRs we)]TJ 24.7126 0 TD -.0011 Tc .0026 Tw [(re co)-4.1(m)10.3(p)-4.1(u)-4.1(t)1.3(ed fo)-4.1(r all )6(o)-4.1(t)1.3(h)-4.1(e)5.6(r maj)-4.7(o)1.9(r can)-4.1(c)-.4(ers )6(n)-4.1(o)1.9(t in)-4.1(clu)-4.1(d)-4.1(e)5.6(d)-4.1( i)7.3(n)-4.1( )]TJ -24.7126 -1.1497 TD -.002 Tc .0035 Tw [(th)-5(e 10)-5( )6(d)-5(i).4(agno)-5(st)6.4(ic g)-5(r)1.7(ou)-5(p)-5(s)3.9( and)-5( )6(sep)-5(a)-1.3(r)-4.3(a)-1.3(tely fo)-5(r no)-5(n-)-4.3(m)9.4(e)-1.3(lan)-5(o)-5(m)9.4(a s)-8(k)-5(in)-5( can)-5(c)-1.3(er)-4.3(s. )24(The h)-5(ypno)-5(tic-)-4.3(a)-1.3(sso)-5(c)-1.3(iated)-5( )6(H)-4.4(R).3(s )6(f)-4.3(o)1(r)-4.3( )]TJ 0 -1.1437 TD .0009 Tc .0006 Tw [(l)3.3(y)-2.1(m)12.3(phom)12.3(as, l)3.3(ung)3.9( cance)7.6(rs,)5.4( col)9.3(o)-2.1(n)3.9( cance)7.6(rs,)5.4( an)3.9(d t)3.3(h)-2.1(e)7.6( al)3.3(l)3.3( ot)9.3(her)4.6( cance)7.6(rs )6(were)7.6( )6(di)3.3(st)3.3(i)3.3(n)-2.1(ct)3.3(l)3.3(y)3.9( el)3.3(evat)3.3(ed, )6(wi)3.3(t)3.3(h)-2.1( )6(95)3.9(% )6(C)3.2(o)-2.1(n)3.9(f)-1.4(i)3.3(d)-2.1(e)7.6(n)-2.1(ce )]TJ 0 -1.1497 TD -.0015 Tc .003 Tw [(In)-4.5(terv)-4.5(als )6(no)-4.5(t ov)-4.5(erlap)-4.5(p)-4.5(i)6.9(n)-4.5(g)1.5( th)-4.5(e )6(HR fo)-4.5(r ca)]TJ 15.6886 0 TD .0004 Tc .0011 Tw [(ncers)6.3( suc)7.1(h)-2.6( as)6.3( leuke)7.1(m)5.8(ia, )-6(m)11.8(e)1.1(lanoma, bl)]TJ 15.1078 0 TD .0001 Tc .0014 Tw [(a)6.8(dde)6.8(r ca)6.8(nc)6.8(ers, )6(uterus/cervix cance)6.8(rs, )]TJ -30.7964 -1.1497 TD .0002 Tc [(breast ca)6.9(nce)6.9(r)-2.1(s, )6(and non-m)11.6(elanom)11.6(a-skin ca)]TJ 16.9341 0 TD .0004 Tc .0011 Tw [(nc)7.1(ers. )24(The)7.1( HR )6(for es)6.3(opha)7.1(geal c)7.1(a)1.1(ncer)]TJ 14.7246 0 TD -.0027 Tc .0042 Tw [(s w)-5.1(a)4(s also)-5.7( )6(h)-5.7(i)-.3(gh)-5.7( an)-5.7(d signif)-5(i)-.3(can)-5.7(t, )6(b)-5.7(u)-5.7(t)-.3( )]TJ -31.6587 -1.1437 TD -.0015 Tc -.003 Tw [(th)-4.5(e )-6(confid)-4.5(en)-4.5(ce in)-4.5(terv)-4.5(al was wi)6.9(d)-4.5(e)-.8( d)-4.5(u)-4.5(e)5.2( )-6(to)-4.5( on)-4.5(ly )-6(2)-4.5(0)1.5( )-6(eso)-4.5(p)1.5(h)-4.5(a)5.2(g)]TJ 22.6467 0 TD -.0003 Tc .0018 Tw [(eal )6(cancers)5.6( bei)8.1(n)-3.3(g )6(obs)5.6(erved. )18(T)5.8(h)-3.3(e )6(HR for prostate cance)6.4(r )6(was )]TJ -22.6467 -1.1497 TD -.0005 Tc .002 Tw [(statistically significant )6(but m)10.9(odest. )6(Neith)]TJ 16.3832 0 TD 0 Tc .0015 Tw [(er te)6.7(mazepam)11.4( nor z)6.7(o)-3(lpidem)11.4( was a)6.7(ssociat)]TJ 16.3174 0 TD -.0005 Tc -.004 Tw [(ed with specific )-6(ca)]TJ 7.4551 0 TD .0003 Tc .0012 Tw [(ncer incide)7(nces )]TJ -40.1557 -1.1497 TD .0017 Tc -.0062 Tw [(si)4.1(gni)4.1(fi)4.1(ca)8.4(nt)4.1(l)4.1(y)4.7( )-6(di)10.1(f)17.3(f)-.6(e)8.4(r)-.6(ent)4.1( fr)5.4(om)13.1( )-6(t)4.1(h)-1.3(at)4.1( )-6(fo)4.7(r user)5.4(s of al)4.1(l)4.1( )-6(hy)4.7(pn)4.7(ot)4.1(i)4.1(c)]TJ 22.3772 0 TD -.0003 Tc .0018 Tw [(s. )6(It was )6(observe)6.4(d)2.7( that the )]TJ 10.6108 0 TD .0019 Tw [(HR as)5.5(sociated )]TJ 5.988 0 TD -.0023 Tc -.0022 Tw [(with)-5.3( hyp)-5.3(no)-5.3(tic )]TJ -38.9761 -1.1437 TD -.0001 Tc .0016 Tw [(presc)6.6(r)-2.4(ibi)8.3(n)-3.1(g exc)6.6(eeded the )6(HR a)6.6(ssociated)]TJ 15.9162 0 TD -.0012 Tc -.0033 Tw [( with)-4.2( cu)-4.2(rren)-4.2(t sm)10.2(o)-4.2(k)-4.2(i)1.2(ng)-4.2( )-6(in )-6(th)-4.2(e sam)10.2(e)-.5( )-6(s)-7.3(t)1.2(ratified)-4.2( p)-4.2(r)2.5(o)-4.2(portio)-4.2(n)-4.2(a)-.5(l )-6(h)-4.2(a)5.5(zard)-4.2(s)-1.3( m)10.2(o)-4.2(d)-4.2(e)-.5(ls )-6(for )]TJ -15.9162 -1.1497 TD .0015 Tc 0 Tw [(l)3.9(y)-1.5(m)12.9(phom)12.9(as, l)3.9(ung)4.5(, c)8.2(o)-1.5(l)3.9(o)4.5(n, )6(p)4.5(r)-.8(os)7.4(t)3.9(a)2.2(t)3.9(e)2.2(, and)4.5( al)3.9(l)3.9( ot)9.9(her)5.2( cance)8.2(rs.)8.2( )6( )]TJ T* 0 Tc ( )Tj /TT12 1 Tf 0 -1.1557 TD 14.1213 Tc ( )Tj ET endstream endobj 176 0 obj <>/Font<>/ProcSet[/PDF/Text]>> endobj 173 0 obj <>stream /GS1 gs BT /TT2 1 Tf 10.98 0 0 10.98 72 745.5601 Tm 0 g 0 Tc 0 Tw ( )Tj 20.8033 -60.9399 TD 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H)5.1(a)2.7(z)6.4(a)-3.3(rd ratios )6(for)18.4( unique)6.4( us)]TJ 22.4132 0 TD -.0005 Tc .002 Tw [(e )6(of )6(8 h)4.8(y)-3.5(pn)4.8(otics \(all doses )6(for)24.2( e)6.2(a)-3.5(ch )6(hypn)4.8(otic\) )]TJ -1.8204 -1.1497 TD 0 Tc 0 Tw ( )Tj -9.3713 -1.1437 TD -.0045 Tw [(Hyp)5.3(n)-.7(otic )]TJ 12.6168 -.5569 TD -.0001 Tc 0 Tw (P )Tj 4.5689 .5569 TD .0019 Tc -.0064 Tw [(HR \()5.6(95%)19.9( )-6(C.I.\))5.6( )]TJ /TT10 1 Tf -23.2275 -2.2515 TD .0017 Tc -.0002 Tw [(No)4.7( hy)10.7(pn)4.7(ot)4.1(i)4.1(c)2.4( u)4.7(s)7.6(e, N=)8.8(2)4.7(3)-1.3(6)4.7(7)4.7(1)-1.3( )6(\(2)4.7(95)4.7( deat)10.1(hs\))5.4( )-826.3(refe)8.4(rence)8.4( )-9754.5( )]TJ 0 -1.1437 TD [(Zol)4.1(p)-1.3(i)10.1(d)-1.3(em)13.1( N=43)4.7(3)4.7(6)-1.3( )6(\(2)4.7(6)4.7(5)-1.3( )6(deat)4.1(hs\))5.4( )-4964.1(.0)4.7(00)4.7( )-3311.4(4.)6.2(82)4.7( \()5.4(4)-1.3(.)6.2(0)4.7(6 t)4.1(o)4.7( 5)4.7(.)6.2(74)4.7(\))5.4( )]TJ 0 -1.1497 TD .0001 Tc -.0046 Tw [(T)72(e)-5.2(m)11.5(azepa)-5.2(m)11.5( )-6(N=2076 \(143 de)6.8(aths)]TJ 13.2156 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.0001 Tw [( )6( N)5(u)-1.6(m)12.8(b)-1.6(er )6(of)5.1( i)3.8(n)-1.6(ci)3.8(de)8.1(nt)3.8( d)4.4(eat)3.8(h)4.4(s)1.3( i)3.8(n)-1.6( t)9.8(h)-1.6(e )6(peri)3.8(o)4.4(d)-1.6( )6(of)5.1( o)4.4(b)-1.6(se)8.1(rvat)3.8(i)3.8(o)4.4(n )6(fo)4.4(r eac)8.1(h )6(hy)4.4(p)4.4(n)-1.6(o)4.4(t)3.8(i)3.8(c)2.1(. )]TJ /TT12 1 Tf 30.3772 0 TD -.0001 Tc 0 Tw (P:)Tj /TT10 1 Tf .9461 0 TD -.0024 Tc .0039 Tw [( )6( pro)-5.4(b)-5.4(a)4.3(bilit)-6(y th)-5.4(at )]TJ -32.3832 -1.1497 TD .0005 Tc .001 Tw [(HR = )6(1 )6(from)11.9( Cox propor)]TJ 9.9701 0 TD .0002 Tc .0013 Tw [(tiona)6.9(l hazards m)11.6(ode)6.9(ls. )]TJ /TT12 1 Tf 9.4491 0 TD -.0054 Tc 0 Tw (HR)Tj /TT10 1 Tf 1.497 0 TD -.0004 Tc -.0041 Tw [( )-6(Haza)6.3(rd ratio )-6(for death. )]TJ /TT12 1 Tf 10.0299 0 TD -.0029 Tc 0 Tw [(C.)-4.4(I.:)]TJ /TT10 1 Tf 1.9401 0 TD -.0017 Tc .0032 Tw [( )6(95)-4.7(% )]TJ -32.8862 -1.1437 TD -.0008 Tc .0023 Tw [(confide)5.9(n)-3.8(ce i)7.6(n)-3.8(terval. )6( )]TJ -3.5928 -1.1497 TD 0 Tc 0 Tw ( )Tj /TT12 1 Tf 0 -1.1617 TD ( )Tj 0 -1.1437 TD .001 Tc .0005 Tw [( )-3341.3(Age)7.7( Ef)4.7(fects)6.9( o)4(n).3( H)6.4(R)-1.4(s )6(for)25.7( De)7.7(a)4(t)-1.3(h )6(and)6.3( C)4.6(a)-2(nce)7.7(r)97.5(. )]TJ 0 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1377 TD ( )Tj /TT10 1 Tf 3.5928 0 TD -.0004 Tc .0019 Tw [(T)71.5(o)-3.4( )6(plot a)6.3(g)-3.4(e e)6.3(f)15.2(fects and acc)6.3(omm)11(odate)]TJ 14.8443 0 TD -.0005 Tc .002 Tw [( li)-4.1(mits i)-4.1(n)-3.5( SPSS pl)7.9(otting ca)6.2(pabilitie)]TJ 13.7844 0 TD -.0013 Tc -.0032 Tw [(s, Cox )-6(proportiona)]TJ 7.4551 0 TD -.0006 Tc .0021 Tw [(l hazards m)10.8(o)-3.6(dels )]TJ -39.6766 -1.1437 TD -.0019 Tc .0034 Tw [(were co)-4.9(m)9.5(p)-4.9(u)-4.9(t).5(ed in)-4.9( )6(wh)-4.9(ich)-4.9( th)-4.9(e co)-4.9(m)9.5(o)-4.9(rb)-4.9(id)-4.9(ity)]TJ 16.4371 0 TD -.0001 Tc .0016 Tw [( classes we)6.6(re im)11.3(ple)-5.4(m)11.3(ented as c)6.6(o)2.9(variates )6(rathe)6.6(r)-2.4( )6(than )6(strata, a)6.6(nd a com)11.3(p)-3.1(lex )]TJ -16.4371 -1.1497 TD [(categorical covariate was 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10.02 0 0 10.02 322.8 492.36 Tm 0 g .0007 Tc 0 Tw [(Refere)7.4(nce)7.4( )]TJ ET q 1 i 374.1 501.54 -5.4 -11.52 re 368.7 501.54 m h 464.22 501.54 -5.4 -11.52 re 458.82 501.54 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 368.7 490.02 95.52 11.52 re f Q .992 .914 .852 rg 374.1 490.02 84.72 11.52 re f BT 10.02 0 0 10.02 458.82 492.36 Tm 0 g .0015 Tc [( )6( )]TJ ET q 1 i 153.18 490.02 -5.4 -11.52 re 147.78 490.02 m h 302.22 490.02 -5.4 -11.52 re 296.82 490.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 147.78 478.5 154.44 11.52 re f Q .992 .914 .852 rg 153.18 478.5 143.64 11.52 re f BT 10.02 0 0 10.02 153.18 480.84 Tm 0 g -.0016 Tc .0031 Tw [( )6(0)-4.6(.)2.9(4)-4.6(-)2.1(18)-4.6( )6(p)-4.6(ills/y)-4.6(r)38(,)-3.1( m)9.8(ean)-4.6( 8)-4.6(,)2.9( N=12)-4.6(00 )]TJ ET q 1 i 307.62 490.02 -5.4 -11.52 re 302.22 490.02 m h 368.7 490.02 -5.4 -11.52 re 363.3 490.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 302.22 478.5 66.48 11.52 re f Q .992 .914 .852 rg 307.62 478.5 55.68 11.52 re f BT 10.02 0 0 10.02 340.14 480.84 Tm 0 g -.0019 Tc 0 Tw [(<.00)-4.9(1 )]TJ ET q 1 i 374.1 490.02 -5.4 -11.52 re 368.7 490.02 m h 464.22 490.02 -5.4 -11.52 re 458.82 490.02 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 368.7 478.5 95.52 11.52 re f Q .992 .914 .852 rg 374.1 478.5 84.72 11.52 re f BT 10.02 0 0 10.02 384.42 480.84 Tm 0 g .0027 Tc -.0012 Tw [(3.)7.2(91)5.7( \()6.4(2)-.3(.)7.2(9)5.7(1 t)5.1(o)5.7( 5)5.7(.)7.2(25)5.7(\))6.4( )]TJ ET q 1 i 153.18 478.5 -5.4 -11.46 re 147.78 478.5 m h 302.22 478.5 -5.4 -11.46 re 296.82 478.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 147.78 467.04 154.44 11.46 re f Q .992 .914 .852 rg 153.18 467.04 143.64 11.46 re f BT 10.02 0 0 10.02 153.18 469.32 Tm 0 g -.0017 Tc .0032 Tw [( )6(1)-4.7(8)1.3(-1)-4.7(32)-4.7( )6(p)-4.7(ills/yr)37.9(,)-3.2( m)9.7(ean)-4.7( 5)-4.7(7)1.3(, )6(N=1)-4.7(289 )]TJ ET q 1 i 307.62 478.5 -5.4 -11.46 re 302.22 478.5 m h 368.7 478.5 -5.4 -11.46 re 363.3 478.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 302.22 467.04 66.48 11.46 re f Q .992 .914 .852 rg 307.62 467.04 55.68 11.46 re f BT 10.02 0 0 10.02 340.14 469.32 Tm 0 g -.0019 Tc 0 Tw [(<.00)-4.9(1 )]TJ ET q 1 i 374.1 478.5 -5.4 -11.46 re 368.7 478.5 m h 464.22 478.5 -5.4 -11.46 re 458.82 478.5 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 368.7 467.04 95.52 11.46 re f Q .992 .914 .852 rg 374.1 467.04 84.72 11.46 re f BT 10.02 0 0 10.02 384.42 469.32 Tm 0 g .0027 Tc -.0012 Tw [(4.)7.2(86)5.7( \()6.4(3)-.3(.)7.2(7)5.7(0 t)5.1(o)5.7( 6)5.7(.)7.2(39)5.7(\))6.4( )]TJ ET q 1 i 153.18 467.04 -5.4 -11.52 re 147.78 467.04 m h 302.22 467.04 -5.4 -11.52 re 296.82 467.04 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 147.78 455.52 154.44 11.52 re f Q .992 .914 .852 rg 153.18 455.52 143.64 11.52 re f BT 10.02 0 0 10.02 153.18 457.86 Tm 0 g -.0019 Tc .0034 Tw [( >1)-4.9(32)-4.9( )6(p)-4.9(ills/yr)37.7(,)-3.4( m)9.5(ean)-4.9( 4)-4.9(6)1.1(9)-4.9(,)-3.4( )6(N=1)-4.9(3)1.1(1)37(1)1.1( )]TJ ET q 1 i 307.62 467.04 -5.4 -11.52 re 302.22 467.04 m h 368.7 467.04 -5.4 -11.52 re 363.3 467.04 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 302.22 455.52 66.48 11.52 re f Q .992 .914 .852 rg 307.62 455.52 55.68 11.52 re f BT 10.02 0 0 10.02 340.14 457.86 Tm 0 g 0 Tw [(<.00)-4.9(1 )]TJ ET q 1 i 374.1 467.04 -5.4 -11.52 re 368.7 467.04 m h 464.22 467.04 -5.4 -11.52 re 458.82 467.04 m W* n 0 792.03 612 -792 re W n .992 .914 .852 rg 368.7 455.52 95.52 11.52 re f Q .992 .914 .852 rg 374.1 455.52 84.72 11.52 re f BT 10.02 0 0 10.02 384.42 457.86 Tm 0 g .0027 Tc -.0012 Tw [(5.)7.2(70)5.7( \()6.4(4)-.3(.)7.2(4)5.7(4 t)5.1(o)5.7( 7)5.7(.)7.2(33)5.7(\))6.4( )]TJ /TT12 1 Tf -23.0778 -1.1617 TD .0005 Tc -.005 Tw [(FEMALES)5.8(: )53.9(An)5.8(y )-6(h)5.8(y)-2.5(p)5.8(n)-.2(o)3.5(t)-1.8(ic )]TJ ET 153.18 444.18 51.72 .95999 re f BT /TT10 1 Tf 10.02 0 0 10.02 340.14 446.34 Tm -.0019 Tc .8297 Tw [(<.00)-4.9(1 )]TJ -18.6587 -1.1497 TD -.0018 Tc .0033 Tw [( )6(N)-4.2(O)1.8( h)-4.8(y)7.2(p)-4.8(n)1.2(o)-4.8(tics, N)-4.2(=)5.3(14)-4.8(837 )-6077.8(Ref)-4.1(e)-1.1(r)-4.1(e)4.9(n)-4.8(c)-1.1(e )-9281.4( )6( )]TJ 0 -1.1437 TD -.002 Tc .0035 Tw [( )6(0)-5(.)2.5(4)-5(-)1.7(18)-5( )6(p)-5(ills/y)-5(r)37.6(,)-3.5( m)9.4(ean)-5( 8)-5(,)2.5( N=22)-5(91 )-4856.3(<.00)-5(1 )-1856.3(3)-5(.)2.5(3)-5(4)1( \(2)-5(.45)-5( to 4.5)-5(6)1(\) )]TJ 0 -1.1497 TD [( )6(1)-5(8)1(-1)-5(32)-5( )6(p)-5(ills/yr)37.6(,)-3.5( m)9.4(ean)-5( 5)-5(7)1(, )6(N=2)-5(259 )-4113.8(<.00)-5(1 )-1856.3(4)-5(.)2.5(2)-5(9)1( \(3)-5(.26)-5( to 5.6)-5(5)1(\) )]TJ T* -.0022 Tc .0037 Tw [( >1)-5.2(32)-5.2( )6(p)-5.2(ills/yr)37.4(,)-3.7( m)9.2(ean)-5.2( 4)-5.2(6).8(9)-5.2(,)-3.7( )6(N)-4.6(=)4.9(2)-5.2(179 )-4377.2(<.00)-5.2(1 )-1856.3(4)-5.2(.)2.3(8)-5.2(8).8( \(3)-5.2(.84)-5.2( to 6.2)-5.2(1).8(\) )]TJ /TT12 1 Tf -8.1018 -1.1557 TD 0 Tc 0 Tw ( )Tj /TT10 1 Tf 0 -1.1377 TD ( )Tj /TT12 1 Tf 0 -1.1617 TD -.0002 Tc .0017 Tw [( )-3341.3(Haz)6.5(a)-3.2(rd )6(Rati)8.2(os for)18.5( )6(8 h)5.1(y)-3.2(p)5.1(n)-.9(otic classes. )]TJ 0 -2.3054 TD 0 Tc 0 Tw ( )Tj /TT10 1 Tf 3.5928 0 TD .0002 Tc .0013 Tw [(T)72.1(o)-2.8( e)6.9(x)-2.8(am)11.6(ine the HR )6(for t)8.6(h)-2.8(e )6(8 )6(hypnotic classe)6.9(s sepa)6.9(ra)]TJ 20.9701 0 TD .0001 Tc [(tely)69(, it was )6(necessa)6.8(ry )6(to com)11.5(pute )6(HR)8.4( enc)6.8(o)-2.9(m)11.5(p)-2.9(asing t)8.5(h)-2.9(e )]TJ -24.5629 -1.3174 TD 0 Tc .0015 Tw [(entire )6(dosa)6.7(g)-3(e )6(range)6.7( for each hypnotic, since)6.7( there)6.7( we)6.7(re )]TJ 22.2335 0 TD -.0003 Tc -.0042 Tw [(too few patients )-6(taking )-6(t)8.1(h)-3.3(e )-6(less popula)6.4(r)-2.6( hypnotic)6.4(s )-6(to )]TJ -22.2335 -1.3174 TD -.0014 Tc .0029 Tw [(reason)-4.4(ab)-4.4(ly d)-4.4(i)1(v)-4.4(i)7(d)-4.4(e)-.7( th)-4.4(ese )6(HR b)-4.4(y)7.6( do)-4.4(sag)-4.4(e)-.7( tertiles. )59.9(An)-4.4(alyses)]TJ 22.5928 0 TD -.0016 Tc .0031 Tw [( of t)6.8(h)-4.6(e )6(8)-4.6( )6(h)-4.6(ypn)-4.6(o)-4.6(tic classes in)-4.6(clud)-4.6(ed th)-4.6(e )6(p)-4.6(a)-.9(tien)-4.6(t).8(s )6(wh)-4.6(o h)-4.6(a)5.1(d)-4.6( )]TJ -22.5928 -1.3234 TD .0009 Tc -.0054 Tw [(t)3.3(a)1.6(ken o)3.9(n)-2.1(l)3.3(y)3.9( )-6(o)3.9(n)-2.1(e hy)3.9(p)3.9(not)3.3(i)3.3(c)1.6( dr)4.6(u)3.9(g)-2.1( cl)3.3(ass )-6(an)3.9(d )-6(e)7.6(x)-2.1(cl)3.3(u)3.9(d)-2.1(ed)3.9( )-6(t)3.3(h)3.9(ose w)4.5(h)-2.1(o)3.9( )]TJ 24 0 TD -.0021 Tc .0036 Tw [(h)-5.1(a)-1.4(d tak)-5.1(e)4.6(n)-5.1( m)9.3(o)-5.1(re th)-5.1(an on)-5.1(e class of)-4.4( )6(h)-5.1(ypn)-5.1(o)-5.1(tic )6(dr)-4.4(ug)-5.1(s. )18(Th)-5.1(ese )]TJ -24 -1.3174 TD -.0013 Tc .0028 Tw [(were an)-4.3(alyses )6(with)-4.3( co)-4.3(m)10.1(o)-4.3(rb)-4.3(id)-4.3(i)7.1(ties stratified)-4.3( fo)-4.3(r u)-4.3(s)-1.4(ers )6(o)-4.3(f)2.4( th)-4.3(at)]TJ 23.6707 0 TD .0017 Tc -.0002 Tw [( pa)8.4(rt)4.1(i)4.1(c)2.4(ul)4.1(ar )6(hy)4.7(p)4.7(not)4.1(i)4.1(c)2.4( cl)4.1(ass,)6.2( a)8.4(n)-1.3(d)4.7( co)4.7(nt)4.1(r)5.4(o)-1.3(l)4.1(l)4.1(e)2.4(d f)5.4(o)4.7(r )6(age, )6(ge)8.4(nde)8.4(r)41.3(,).2( )]TJ -23.6707 -1.3234 TD .0015 Tc -.006 Tw [(sm)12.9(oki)3.9(ng,)6( )-6(et)3.9(c. )-6( )18(The deat)3.9(h)4.5( )-6(HR)3.8( fo)4.5(r 8 hy)4.5(p)]TJ 15.3413 0 TD -.0024 Tc .0039 Tw [(n)-5.4(o)-5.4(tic )6(classes ar)-4.7(e )6(show)-4.8(n in)-5.4( )6(Supp)-5.4(lemen)-5.4(t)0(ar)-4.7(y )18(T)69.5(a)-1.7(b)-5.4(l)0(e 9. )18(Th)-5.4(e )6(H)-4.8(R)-.1( 95)-5.4(% )6(Co)-5.4(nf)-4.7(id)-5.4(en)-5.4(ce )]TJ -15.3413 -1.3174 TD .0014 Tc .0001 Tw [(Int)3.8(e)2.1(r)5.1(v)-1.6(al)3.8( )6(fo)4.4(r )6(6 )6(o)4.4(f)-.9( t)3.8(h)-1.6(e)8.1( ot)9.8(her )6(hy)4.4(p)4.4(not)3.8(i)3.8(c)2.1(s i)9.8(n)-1.6(cl)3.8(u)4.4(d)-1.6(ed)4.4( t)3.8(h)-1.6(e m)12.8(ean HR)3.7( )6(f)5.1(o)-1.6(r)5.1( zol)9.8(p)-1.6(i)3.8(d)-1.6(em)12.8(, so t)3.8(h)-1.6(e)8.1(s)1.3(e )6(dr)5.1(ug)4.4(s )6(d)4.4(i)3.8(d n)4.4(o)-1.6(t)3.8( )6(have)8.1( a si)9.8(gni)9.8(fi)3.8(cant)3.8(l)3.8(y)4.4( )]TJ T* .0003 Tc .0012 Tw [(dif)15.9(f)-2(e)7(r)-2(e)7(n)-2.7(t deat)8.7(h )6(hazard )6(from)11.7( that of zol)8.7(p)-2.7(idem)11.7(. )18(T)6.4(h)-2.7(e e)7(x)-2.7(cep)]TJ 22.5808 0 TD .0005 Tc .001 Tw [(tion )6(was esz)7.2(o)3.5(piclone)7.2(, )6(whic)7.2(h )6(had an e)7.2(s).4(tim)11.9(a)1.2(ted death HR)8.8( of )]TJ -22.5808 -1.3234 TD .0017 Tc -.0062 Tw [(30)4.7(.6)4.7(2 \()5.4(1)-1.3(2)4.7(.).2(9)4.7(0)-1.3(-)5.4(7)4.7(2.)6.2(72)4.7(, 95)4.7(% )-6(C)4(o)4.7(n)4.7(f)-.6(i)4.1(d)-1.3(e)8.4(n)-1.3(ce )-6(I)5.4(n)-1.3(t)4.1(e)2.4(r)5.4(v)]TJ 17.4671 0 TD .0001 Tc .0014 Tw [(a)6.8(l)2.5(.\) )18(T)6.2(h)-2.9(e e)6.8(x)-2.9(trem)11.5(e elevation )6(of t)8.5(h)-2.9(e esz)6.8(o)3.1(piclone)6.8( death HR)8.4( is di)8.5(f)15.7(f)-2.2(icult t)8.5(o)-2.9( )]TJ -17.4671 -1.3174 TD 0 Tc .0015 Tw [(interpret because there)6.7( we)6.7(re )6(only 6 )6(d)]TJ 14.7485 0 TD -.0003 Tc .0018 Tw [(eaths a)6.4(m)11.1(ong the )6(sm)11.1(all group prescri)8.1(b)-3.3(ed on)]TJ 17.1257 0 TD .0002 Tc .0013 Tw [(ly esz)6.9(o)-2.8(piclone, a)6.9(n)3.2(d t)8.6(h)-2.8(eir )6(periods)6.1( of )]TJ -31.8743 -1.3234 TD -.0002 Tc .0017 Tw [(obs)5.7(ervation average)6.5(d)-3.2( )6(only 0.79)]TJ 12.5329 0 TD -.0001 Tc .0016 Tw [( years, pa)6.6(rtly because esz)6.6(o)]TJ 10.6108 0 TD .0003 Tc -.0048 Tw [(piclone)7( )-6(wa)7(s not )-12(m)11.7(a)1(rketed be)7(fo)]TJ 12.2515 0 TD .0006 Tc .0009 Tw [(re)7.3( m)12(i)3(d-2005. )6( Note that )]TJ -35.3952 -1.3174 TD .0015 Tc 0 Tw [(pat)3.9(i)3.9(e)2.2(nt)3.9(s )6(presc)8.2(r)-.8(i)9.9(b)-1.5(ed)4.5( hy)10.5(pn)4.5(ot)3.9(i)3.9(c)2.2(s )6(were)8.2( n)4.5(o)-1.5(t)3.9( ra)8.2(n)4.5(d)-1.5(o)4.5(m)6.9(l)3.9(y)4.5( assi)3.9(gned t)9.9(o)-1.5( t)3.9(h)-1.5(e)8.2( di)9.9(f)17.1(f)-.8(e)8.2(r)-.8(ent)3.9( )6(dr)5.2(u)4.5(g)-1.5(s, a)8.2(n)4.5(d t)3.9(h)-1.5(e)8.2(r)5.2(e m)12.9(a)-3.8(y)4.5( have )6(be)8.2(en )6(bi)3.9(ases )6(fo)4.5(r )]TJ T* [(part)3.9(i)3.9(c)2.2(ul)3.9(a)8.2(r)-.8( )6(dr)5.2(ug)4.5(s i)3.9(n)-1.5( )6(pre)8.2(s)1.4(cri)3.9(b)-1.5(i)9.9(n)4.5(g am)12.9(ong)4.5( pat)3.9(i)3.9(e)8.2(nt)3.9(s )6(of )6(va)8.2(ry)4.5(i)3.9(n)-1.5(g)4.5( )6(ages,)6( ge)8.2(n)4.5(d)-1.5(ers)7.4(,)0( )6(sm)12.9(oki)3.9(ng st)3.9(at)3.9(u)4.5(s)7.4(, et)3.9(c., a)8.2(s)1.4( )6(wel)3.9(l)3.9( as di)3.9(f)23.1(f)-.8(eri)9.9(n)-1.5(g)4.5( )]TJ 0 -1.3234 TD .0013 Tc .0002 Tw [(num)12.7(bers )6(o)4.3(f)-1( )6(hy)4.3(pn)4.3(ot)3.7(i)3.7(c)2( d)4.3(o)-1.7(ses)7.2( re)8(cei)3.7(ved )6(by)4.3( )6(pat)3.7(i)3.7(e)2(nt)3.7(s i)3.7(n)4.3( di)3.7(f)22.9(f)-1(ere)8(n)-1.7(t)3.7( )6(dr)5(u)4.3(g)-1.7( cl)3.7(asses.)5.8( )24(The c)8(o)4.3(nt)3.7(rol)3.7( )6(co)4.3(ho)4.3(rt)3.7(s )6(were)8( n)4.3(o)-1.7(t)3.7( )6(ext)3.7(r)-1(act)3.7(ed)4.3( f)5(o)-1.7(r)5( )]TJ 0 -1.3174 TD .0015 Tc 0 Tw [(m)6.9(a)2.2(t)3.9(c)2.2(hi)3.9(ng t)9.9(o)-1.5( t)3.9(h)4.5(e pa)8.2(rt)3.9(i)3.9(c)2.2(ul)3.9(ar c)8.2(o)4.5(ho)4.5(rt)3.9(s t)3.9(a)2.2(ki)9.9(ng)4.5( ea)8.2(ch si)9.9(ngl)3.9(e cl)3.9(ass)7.4( )6(of)5.2( hy)10.5(pn)4.5(ot)3.9(i)3.9(c)2.2(. )18(T)7.6(hus)7.4(, al)3.9(t)3.9(h)4.5(o)4.5(u)-1.5(g)4.5(h)-1.5( t)9.9(h)-1.5(e a)8.2(n)-1.5(al)3.9(y)4.5(s)1.4(es i)3.9(n)-1.5( )24(T)73.4(a)2.2(bl)3.9(e 9)4.5( we)8.2(re )]TJ 0 -1.3234 TD .0014 Tc .0001 Tw [(st)3.8(rat)3.8(i)3.8(f)-.9(i)3.8(e)2.1(d f)5.1(o)4.4(r c)8.1(o)-1.6(m)12.8(o)-1.6(rbi)3.8(d)-1.6(i)3.8(t)3.8(y)4.4( cl)3.8(asses f)5.1(o)-1.6(r)5.1( eac)8.1(h )6(d)4.4(r)-.9(u)4.4(g)-1.6( a)8.1(n)4.4(d c)8.1(ont)3.8(r)5.1(o)-1.6(l)9.8(l)3.8(ed f)5.1(o)-1.6(r)5.1( co)4.4(va)8.1(ri)3.8(at)3.8(es, c)8.1(o)-1.6(m)12.8(p)-1.6(ari)3.8(s)1.3(on)4.4(s o)4.4(f)-.9( )6(HR)3.7( bet)9.8(w)-1(e)8.1(e)2.1(n i)3.8(n)4.4(di)3.8(vi)9.8(du)4.4(al)3.8( )]TJ 0 -1.3174 TD .0002 Tw [(hy)4.3(p)4.3(not)3.7(i)3.7(c)2( cl)3.7(asse)8(s co)4.3(ul)3.7(d)4.3( be)8( m)12.7(i)3.7(sleadi)3.7(n)4.3(g. )24(Thi)3.7(s)1.2( m)12.7(a)2(y)4.3( have)8( bee)8(n)-1.7( )6(p)4.3(a)2(rt)3.7(i)3.7(c)2(ul)3.7(arl)3.7(y)4.3( a c)8(o)4.3(ncer)5(n )6(fo)4.3(r )6(bar)5(b)-1.7(i)9.7(t)3.7(urat)3.7(es a)8(n)-1.7(d)4.3( ant)3.7(i)9.7(hi)3.7(st)3.7(am)6.7(i)3.7(n)-1.7(es, )]TJ T* .0002 Tc .0013 Tw [(for )6(whic)6.9(h the)6.9( prescri)8.6(b)-2.8(ing inte)6.9(ntions )]TJ 14.503 0 TD 0 Tc .0015 Tw [(m)11.4(a).7(y not ha)6.7(ve )6(been fully com)11.4(p)-3(arable )]TJ 14.8024 0 TD [(t)8.4(o)-3( those)6.7( for the )6(benz)6.7(odiazepi)8.4(n)3(es and )]TJ -29.3054 -1.3234 TD .0001 Tc .0014 Tw [(benz)6.8(odiazepi)8.5(n)3.1(e agonists.)]TJ /TT12 1 Tf 9.976 0 TD 14.1213 Tc 0 Tw ( )Tj ET endstream endobj 172 0 obj <>/Font<>/ProcSet[/PDF/Text]>> endobj 124 0 obj <> endobj 125 0 obj <> endobj 126 0 obj <> endobj 127 0 obj <> endobj 128 0 obj <> endobj 189 0 obj <>stream /GS1 gs BT /TT2 1 Tf 10.98 0 0 10.98 72 745.5601 Tm 0 g 0 Tc 0 Tw ( )Tj 20.8033 -60.9399 TD .0014 Tc (10 )Tj -20.8033 -2.3169 TD 0 Tc ( )Tj /TT12 1 Tf 10.02 0 0 10.02 72 710.7 Tm ( )Tj 0 -1.1497 TD .0001 Tc .0014 Tw [( )-3341.3(Haz)6.8(a)-2.9(rd r)6.8(a)3.1(tios)6( for)18.8( su)5.4(bsampl)8.5(es diag)]TJ 18.2156 0 TD -.0006 Tc -.0039 Tw [(n)4.7(o)-3.6(sed)4.7( with )-6(specific d)4.7(i)1.8(sease )-6(classes. )]TJ -18.2156 -1.1437 TD 0 Tc 0 Tw ( )Tj 0 -1.1377 TD ( )Tj /TT10 1 Tf 3.5928 0 TD -.0012 Tc .0027 Tw [(T)70.7(o)-4.2( furth)-4.2(e)-.5(r ex)-4.2(amin)-4.2(e an)-4.2(y influen)-4.2(ce )6(o)-4.2(f)2.5( 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[(m)9.9(o)-4.5(st lik)-4.5(ely d)-4.5(u)-4.5(e)-.8( to)-4.5( th)-4.5(e sm)9.9(all s)-7.5(a)-6.8(m)9.9(p)-4.5(le size, so)-4.5( )6(th)-4.5(at d)-4.5(i).9(sease )6(class is no)-4.5(t sho)-4.5(w)2.1(n. )]TJ 0 -1.1497 TD 0 Tc 0 Tw ( )Tj /TT2 1 Tf 10.98 0 0 10.98 306 594.54 Tm ( )Tj /TT12 1 Tf 10.02 0 0 10.02 130.92 582.3 Tm .0015 Tw [(Supplemen)5.3(tar)6.7(y)-3( )18(T)98.1(a)-3(ble )6(7: )59.9(Ad)5.3(juste)6.7(d)-.7( h)5.3(a)-3(z)6.7(a)-3(rd )6(ra)]TJ 18.9701 0 TD -.0002 Tc .0017 Tw [(ti)8.2(os )6(\(95)-9.2(%)17.8( confid)5.1(ence limits\) )6(for)18.5( de)6.5(ath)5.1( )]TJ -19.497 -1.1497 TD .0015 Tc 0 Tw [(fr)20.2(om)8.2( C)5.1(o)4.5(x r)20.2(e)8.2(gr)26.2(essi)3.9(on)6.8(* f)5.2(o)-1.5(r)26.2( su)6.8(bpo)4.5(pul)3.9(a)4.5(t)-.8(i)3.9(o)-1.5(n)6.8(s)1.4( )6(defi)]TJ 19.2515 0 TD -.0006 Tc .0021 Tw [(ned by the)6.1( pr)18.1(esence)6.1( of s)5.3(p)-1.3(ecific disease)6.1(s)-.7(, )]TJ -16.006 -1.1497 TD .0022 Tw [(comparing ter)6(t)-3(iles of user)6(s )6(of )6(any hy)]TJ 15.5269 0 TD -.0005 Tc .002 Tw [(pnotic with nonuser)6.2(s)-.6( \(r)18.2(e)6.2(f)-2.8(er)18.2(ence)6.2(\). )]TJ /TT10 1 Tf -24.1257 -1.1317 TD 0 Tc 0 Tw ( )Tj ET 1 g 72 521.52 124.56 24.06 re f BT /TT18 1 Tf 10.02 0 0 10.02 72 524.28 Tm 0 g -.0006 Tc -.0039 Tw (Disease class )Tj ET q 1 i 232.68 545.58 -36.12 -5.88 re 196.56 545.58 m h 232.68 527.46 -36.12 -5.94 re 196.56 527.46 m W* n 0 792.03 612 -792 re W n 1 g 196.56 521.52 36.12 24.06 re f Q 1 g 196.56 527.46 36.12 12.24 re f BT 10.02 0 0 10.02 211.32 530.22 Tm 0 g 0 Tc 0 Tw (N )Tj ET 1 g 232.68 521.52 285.54 24.06 re f BT 10.02 0 0 10.02 332.82 536.16 Tm 0 g -.0007 Tc .0022 Tw [(Pills )6(per y)11.9(e)-.3(ar \()5.4(m)-1.6(ean)]TJ /TT2 1 Tf 8.2036 0 TD 0 Tc 0 Tw (\))Tj ET q 1 i 72 521.52 m 72 508.32 l 77.4 508.32 l 77.4 520.56 l 191.16 520.56 l 191.16 508.32 l 196.56 508.32 l 196.56 521.52 l W* n 0 792.03 612 -792 re W n 1 g 72 508.32 124.56 13.2 re f Q 1 g 77.4 508.32 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 511.08 Tm 0 g ( )Tj ET q 1 i 196.56 521.52 m 196.56 508.32 l 201.96 508.32 l 201.96 520.56 l 227.28 520.56 l 227.28 508.32 l 232.68 508.32 l 232.68 521.52 l W* n 0 792.03 612 -792 re W n 1 g 196.56 508.32 36.12 13.2 re f Q 1 g 201.96 508.32 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 214.62 511.08 Tm 0 g ( )Tj ET q 1 i 232.68 521.52 m 232.68 508.32 l 238.08 508.32 l 238.08 520.56 l 322.32 520.56 l 322.32 508.32 l 327.72 508.32 l 327.72 521.52 l W* n 0 792.03 612 -792 re W n 1 g 232.68 508.32 95.04 13.2 re f Q 1 g 238.08 508.32 84.24 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 255.3 511.08 Tm 0 g .0014 Tc .0001 Tw [(0.)5(4 t)12.8(o).1( )6(1)5.2(8)-.7( \(8)5.2(\))7.5( )]TJ ET q 1 i 327.72 521.52 m 327.72 508.32 l 333.12 508.32 l 333.12 520.56 l 417.3 520.56 l 417.3 508.32 l 422.7 508.32 l 422.7 521.52 l W* n 0 792.03 612 -792 re W n 1 g 327.72 508.32 94.98 13.2 re f Q 1 g 333.12 508.32 84.18 12.24 re f BT 10.02 0 0 10.02 346.56 511.08 Tm 0 g .0015 Tc 0 Tw [(18 t)18.8(o).2( 1)5.3(3)5.3(2)-.6( \(5)5.3(7\))7.6( )]TJ ET q 1 i 422.7 521.52 m 422.7 508.32 l 428.1 508.32 l 428.1 520.56 l 512.82 520.56 l 512.82 508.32 l 518.22 508.32 l 518.22 521.52 l W* n 0 792.03 612 -792 re W n 1 g 422.7 508.32 95.52 13.2 re f Q 1 g 428.1 508.32 84.72 12.24 re f BT 10.02 0 0 10.02 448.5 511.08 Tm 0 g -.0042 Tc .0057 Tw [(>1)-6.3(32)-6.3( \(4)-6.3(69)-6.3(\) )]TJ ET q 1 i 72 508.32 m 72 495.12 l 77.4 495.12 l 77.4 507.36 l 191.16 507.36 l 191.16 495.12 l 196.56 495.12 l 196.56 508.32 l W* n 0 792.03 612 -792 re W n 1 g 72 495.12 124.56 13.2 re f Q 1 g 77.4 495.12 113.76 12.24 re f BT 10.02 0 0 10.02 77.4 497.88 Tm 0 g -.0004 Tc 0 Tw [(Hypert)10.9(en)3.3(sio)4.3(n)3.3( )]TJ ET q 1 i 196.56 508.32 m 196.56 495.12 l 201.96 495.12 l 201.96 507.36 l 227.28 507.36 l 227.28 495.12 l 232.68 495.12 l 232.68 508.32 l W* n 0 792.03 612 -792 re W n 1 g 196.56 495.12 36.12 13.2 re f Q 1 g 201.96 495.12 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 201.96 497.88 Tm 0 g .0021 Tc [(13)5.9(11)5.9(6)5.9( )]TJ ET q 1 i 232.68 508.32 m 232.68 495.12 l 238.08 495.12 l 238.08 507.36 l 322.32 507.36 l 322.32 495.12 l 327.72 495.12 l 327.72 508.32 l W* n 0 792.03 612 -792 re W n 1 g 232.68 495.12 95.04 13.2 re f Q 1 g 238.08 495.12 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 497.88 Tm 0 g .0011 Tc .0004 Tw [(4.1)4.9(4)-1( \()4.9(3)-1(.1)4.9(7 t)12.7(o)1.5( )6(5.)8(40)4.9(\))4.9( )]TJ ET q 1 i 327.72 508.32 m 327.72 495.12 l 333.12 495.12 l 333.12 507.36 l 417.3 507.36 l 417.3 495.12 l 422.7 495.12 l 422.7 508.32 l W* n 0 792.03 612 -792 re W n 1 g 327.72 495.12 94.98 13.2 re f Q 1 g 333.12 495.12 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 497.88 Tm 0 g [(5.9)4.9(0)-1( \()4.9(4)-1(.6)4.9(8 t)12.7(o)1.5( )6(7.)8(45)4.9(\))4.9( )]TJ ET q 1 i 422.7 508.32 m 422.7 495.12 l 428.1 495.12 l 428.1 507.36 l 512.82 507.36 l 512.82 495.12 l 518.22 495.12 l 518.22 508.32 l W* n 0 792.03 612 -792 re W n 1 g 422.7 495.12 95.52 13.2 re f Q 1 g 428.1 495.12 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 497.88 Tm 0 g -.0036 Tc .0051 Tw [(5)-5.7(.)-2.7(85)-5.7( \(4)-5.7(.74)-5.7( t)8(o)-3.2( )6(7)-5.8(.)3.3(2)-5.8(3\) )]TJ ET q 1 i 72 495.12 m 72 481.92 l 77.4 481.92 l 77.4 494.16 l 191.16 494.16 l 191.16 481.92 l 196.56 481.92 l 196.56 495.12 l W* n 0 792.03 612 -792 re W n 1 g 72 481.92 124.56 13.2 re f Q 1 g 77.4 481.92 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 484.68 Tm 0 g -.0004 Tc .0019 Tw [(P)16.9(e)0(ptic Ul)5.7(cer Di)5.7(sease)6( )]TJ ET q 1 i 196.56 495.12 m 196.56 481.92 l 201.96 481.92 l 201.96 494.16 l 227.28 494.16 l 227.28 481.92 l 232.68 481.92 l 232.68 495.12 l W* n 0 792.03 612 -792 re W n 1 g 196.56 481.92 36.12 13.2 re f Q 1 g 201.96 481.92 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 484.68 Tm 0 g .0021 Tc 0 Tw [(62)5.9(86)5.9( )]TJ ET q 1 i 232.68 495.12 m 232.68 481.92 l 238.08 481.92 l 238.08 494.16 l 322.32 494.16 l 322.32 481.92 l 327.72 481.92 l 327.72 495.12 l W* n 0 792.03 612 -792 re W n 1 g 232.68 481.92 95.04 13.2 re f Q 1 g 238.08 481.92 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 484.68 Tm 0 g .0011 Tc .0004 Tw [(3.7)4.9(2)-1( \()4.9(2)-1(.3)4.9(5 t)12.7(o)1.5( )6(5.)8(87)4.9(\))4.9( )]TJ ET q 1 i 327.72 495.12 m 327.72 481.92 l 333.12 481.92 l 333.12 494.16 l 417.3 494.16 l 417.3 481.92 l 422.7 481.92 l 422.7 495.12 l W* n 0 792.03 612 -792 re W n 1 g 327.72 481.92 94.98 13.2 re f Q 1 g 333.12 481.92 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 484.68 Tm 0 g [(5.7)4.9(3)-1( \()4.9(3)-1(.8)4.9(1 t)12.7(o)1.5( )6(8.)8(62)4.9(\))4.9( )]TJ ET q 1 i 422.7 495.12 m 422.7 481.92 l 428.1 481.92 l 428.1 494.16 l 512.82 494.16 l 512.82 481.92 l 518.22 481.92 l 518.22 495.12 l W* n 0 792.03 612 -792 re W n 1 g 422.7 481.92 95.52 13.2 re f Q 1 g 428.1 481.92 84.72 12.24 re f BT 10.02 0 0 10.02 429.48 484.68 Tm 0 g .0013 Tc .0002 Tw [( 7.2)5.1(7)-.8( )6(\(5.)8.2(1)-.8(4 t)12.9(o)7.7( 1)5.1(0)-.8(.2)5.1(9\))5.1( )]TJ ET q 1 i 72 481.92 m 72 468.72 l 77.4 468.72 l 77.4 480.96 l 191.16 480.96 l 191.16 468.72 l 196.56 468.72 l 196.56 481.92 l W* n 0 792.03 612 -792 re W n 1 g 72 468.72 124.56 13.2 re f Q 1 g 77.4 468.72 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 471.48 Tm 0 g -.0024 Tc 0 Tw [(Diabet)9(es )]TJ ET q 1 i 196.56 481.92 m 196.56 468.72 l 201.96 468.72 l 201.96 480.96 l 227.28 480.96 l 227.28 468.72 l 232.68 468.72 l 232.68 481.92 l W* n 0 792.03 612 -792 re W n 1 g 196.56 468.72 36.12 13.2 re f Q 1 g 201.96 468.72 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 471.48 Tm 0 g .0021 Tc [(52)5.9(15)5.9( )]TJ ET q 1 i 232.68 481.92 m 232.68 468.72 l 238.08 468.72 l 238.08 480.96 l 322.32 480.96 l 322.32 468.72 l 327.72 468.72 l 327.72 481.92 l W* n 0 792.03 612 -792 re W n 1 g 232.68 468.72 95.04 13.2 re f Q 1 g 238.08 468.72 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 471.48 Tm 0 g .0011 Tc .0004 Tw [(5.2)4.9(3)-1( \()4.9(3)-1(.7)4.9(2 t)12.7(o)1.5( )6(7.)8(37)4.9(\))4.9( )]TJ ET q 1 i 327.72 481.92 m 327.72 468.72 l 333.12 468.72 l 333.12 480.96 l 417.3 480.96 l 417.3 468.72 l 422.7 468.72 l 422.7 481.92 l W* n 0 792.03 612 -792 re W n 1 g 327.72 468.72 94.98 13.2 re f Q 1 g 333.12 468.72 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 471.48 Tm 0 g [(5.1)4.9(6)-1( \()4.9(3)-1(.7)4.9(2 t)12.7(o)1.5( )6(7.)8(14)4.9(\))4.9( )]TJ ET q 1 i 422.7 481.92 m 422.7 468.72 l 428.1 468.72 l 428.1 480.96 l 512.82 480.96 l 512.82 468.72 l 518.22 468.72 l 518.22 481.92 l W* n 0 792.03 612 -792 re W n 1 g 422.7 468.72 95.52 13.2 re f Q 1 g 428.1 468.72 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 471.48 Tm 0 g -.0036 Tc .0051 Tw [(6)-5.7(.)-2.7(78)-5.7( \(5)-5.7(.08)-5.7( t)8(o)-3.2( )6(9)-5.8(.)3.3(0)-5.8(3\) )]TJ ET q 1 i 72 468.72 m 72 455.52 l 77.4 455.52 l 77.4 467.76 l 191.16 467.76 l 191.16 455.52 l 196.56 455.52 l 196.56 468.72 l W* n 0 792.03 612 -792 re W n 1 g 72 455.52 124.56 13.2 re f Q 1 g 77.4 455.52 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 458.28 Tm 0 g -.0003 Tc .0018 Tw [(Car)13.9(d)-2.6(iov)11.8(a)8.3(scu)3.4(l)-.2(ar Disease)6.1( )]TJ ET q 1 i 196.56 468.72 m 196.56 455.52 l 201.96 455.52 l 201.96 467.76 l 227.28 467.76 l 227.28 455.52 l 232.68 455.52 l 232.68 468.72 l W* n 0 792.03 612 -792 re W n 1 g 196.56 455.52 36.12 13.2 re f Q 1 g 201.96 455.52 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 458.28 Tm 0 g .0021 Tc 0 Tw [(54)5.9(51)5.9( )]TJ ET q 1 i 232.68 468.72 m 232.68 455.52 l 238.08 455.52 l 238.08 467.76 l 322.32 467.76 l 322.32 455.52 l 327.72 455.52 l 327.72 468.72 l W* n 0 792.03 612 -792 re W n 1 g 232.68 455.52 95.04 13.2 re f Q 1 g 238.08 455.52 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 458.28 Tm 0 g .0011 Tc .0004 Tw [(3.9)4.9(4)-1( \()4.9(3)-1(.0)4.9(1 t)12.7(o)1.5( )6(5.)8(16)4.9(\))4.9( )]TJ ET q 1 i 327.72 468.72 m 327.72 455.52 l 333.12 455.52 l 333.12 467.76 l 417.3 467.76 l 417.3 455.52 l 422.7 455.52 l 422.7 468.72 l W* n 0 792.03 612 -792 re W n 1 g 327.72 455.52 94.98 13.2 re f Q 1 g 333.12 455.52 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 458.28 Tm 0 g [(5.0)4.9(5)-1( \()4.9(3)-1(.9)4.9(6 t)12.7(o)1.5( )6(6.)8(43)4.9(\))4.9( )]TJ ET q 1 i 422.7 468.72 m 422.7 455.52 l 428.1 455.52 l 428.1 467.76 l 512.82 467.76 l 512.82 455.52 l 518.22 455.52 l 518.22 468.72 l W* n 0 792.03 612 -792 re W n 1 g 422.7 455.52 95.52 13.2 re f Q 1 g 428.1 455.52 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 458.28 Tm 0 g -.0036 Tc .0051 Tw [(5)-5.7(.)-2.7(70)-5.7( \(4)-5.7(.59)-5.7( t)8(o)-3.2( )6(7)-5.8(.)3.3(0)-5.8(7\) )]TJ ET q 1 i 72 455.52 m 72 442.32 l 77.4 442.32 l 77.4 454.56 l 191.16 454.56 l 191.16 442.32 l 196.56 442.32 l 196.56 455.52 l W* n 0 792.03 612 -792 re W n 1 g 72 442.32 124.56 13.2 re f Q 1 g 77.4 442.32 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 445.08 Tm 0 g -.0004 Tc .0019 Tw [(Cor)13.8(o)-1.7(nary Hear)7.8(t Diseas)3.3(e)6( )]TJ ET q 1 i 196.56 455.52 m 196.56 442.32 l 201.96 442.32 l 201.96 454.56 l 227.28 454.56 l 227.28 442.32 l 232.68 442.32 l 232.68 455.52 l W* n 0 792.03 612 -792 re W n 1 g 196.56 442.32 36.12 13.2 re f Q 1 g 201.96 442.32 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 445.08 Tm 0 g .0021 Tc 0 Tw [(36)5.9(63)5.9( )]TJ ET q 1 i 232.68 455.52 m 232.68 442.32 l 238.08 442.32 l 238.08 454.56 l 322.32 454.56 l 322.32 442.32 l 327.72 442.32 l 327.72 455.52 l W* n 0 792.03 612 -792 re W n 1 g 232.68 442.32 95.04 13.2 re f Q 1 g 238.08 442.32 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 445.08 Tm 0 g .0011 Tc .0004 Tw [(4.6)4.9(3)-1( \()4.9(3)-1(.2)4.9(9 t)12.7(o)1.5( )6(6.)8(52)4.9(\))4.9( )]TJ ET q 1 i 327.72 455.52 m 327.72 442.32 l 333.12 442.32 l 333.12 454.56 l 417.3 454.56 l 417.3 442.32 l 422.7 442.32 l 422.7 455.52 l W* n 0 792.03 612 -792 re W n 1 g 327.72 442.32 94.98 13.2 re f Q 1 g 333.12 442.32 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 445.08 Tm 0 g [(5.4)4.9(3)-1( \()4.9(3)-1(.9)4.9(6 t)12.7(o)1.5( )6(7.)8(43)4.9(\))4.9( )]TJ ET q 1 i 422.7 455.52 m 422.7 442.32 l 428.1 442.32 l 428.1 454.56 l 512.82 454.56 l 512.82 442.32 l 518.22 442.32 l 518.22 455.52 l W* n 0 792.03 612 -792 re W n 1 g 422.7 442.32 95.52 13.2 re f Q 1 g 428.1 442.32 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 445.08 Tm 0 g -.0036 Tc .0051 Tw [(6)-5.7(.)-2.7(60)-5.7( \(5)-5.7(.00)-5.7( t)8(o)-3.2( )6(8)-5.8(.)3.3(7)-5.8(1\) )]TJ ET q 1 i 72 442.32 m 72 429.12 l 77.4 429.12 l 77.4 441.36 l 191.16 441.36 l 191.16 429.12 l 196.56 429.12 l 196.56 442.32 l W* n 0 792.03 612 -792 re W n 1 g 72 429.12 124.56 13.2 re f Q 1 g 77.4 429.12 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 431.88 Tm 0 g -.0002 Tc 0 Tw [(Obesity)6.4( )]TJ ET q 1 i 196.56 442.32 m 196.56 429.12 l 201.96 429.12 l 201.96 441.36 l 227.28 441.36 l 227.28 429.12 l 232.68 429.12 l 232.68 442.32 l W* n 0 792.03 612 -792 re W n 1 g 196.56 429.12 36.12 13.2 re f Q 1 g 201.96 429.12 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 431.88 Tm 0 g .0021 Tc [(26)5.9(65)5.9( )]TJ ET q 1 i 232.68 442.32 m 232.68 429.12 l 238.08 429.12 l 238.08 441.36 l 322.32 441.36 l 322.32 429.12 l 327.72 429.12 l 327.72 442.32 l W* n 0 792.03 612 -792 re W n 1 g 232.68 429.12 95.04 13.2 re f Q 1 g 238.08 429.12 84.24 12.24 re f BT 10.02 0 0 10.02 238.08 431.88 Tm 0 g -.0005 Tw [( 8.)8.9(07 )6(\(3.)8.9(6)-.1(4)5.8( t)13.6(o)2.4( )6(17.)8.9(89)5.8(\))5.8( )]TJ ET q 1 i 327.72 442.32 m 327.72 429.12 l 333.12 429.12 l 333.12 441.36 l 417.3 441.36 l 417.3 429.12 l 422.7 429.12 l 422.7 442.32 l W* n 0 792.03 612 -792 re W n 1 g 327.72 429.12 94.98 13.2 re f Q 1 g 333.12 429.12 84.18 12.24 re f BT 10.02 0 0 10.02 333.12 431.88 Tm 0 g [( 6.)8.9(37 )6(\(2.)8.9(7)-.1(3)5.8( t)13.6(o)2.4( )6(14.)8.9(88)5.8(\))5.8( )]TJ ET q 1 i 422.7 442.32 m 422.7 429.12 l 428.1 429.12 l 428.1 441.36 l 512.82 441.36 l 512.82 429.12 l 518.22 429.12 l 518.22 442.32 l W* n 0 792.03 612 -792 re W n 1 g 422.7 429.12 95.52 13.2 re f Q 1 g 428.1 429.12 84.72 12.24 re f BT 10.02 0 0 10.02 429.48 431.88 Tm 0 g .0013 Tc .0002 Tw [( 9.3)5.1(4)-.8( )6(\(4.)8.2(4)-.8(7 t)12.9(o)7.7( 1)5.1(9)-.8(.5)5.1(2\))5.1( )]TJ ET q 1 i 72 429.12 m 72 415.92 l 77.4 415.92 l 77.4 428.16 l 191.16 428.16 l 191.16 415.92 l 196.56 415.92 l 196.56 429.12 l W* n 0 792.03 612 -792 re W n 1 g 72 415.92 124.56 13.2 re f Q 1 g 77.4 415.92 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 418.68 Tm 0 g -.0012 Tc 0 Tw [(As)8.5(thma )]TJ ET q 1 i 196.56 429.12 m 196.56 415.92 l 201.96 415.92 l 201.96 428.16 l 227.28 428.16 l 227.28 415.92 l 232.68 415.92 l 232.68 429.12 l W* n 0 792.03 612 -792 re W n 1 g 196.56 415.92 36.12 13.2 re f Q 1 g 201.96 415.92 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 418.68 Tm 0 g .0021 Tc [(21)5.9(93)5.9( )]TJ ET q 1 i 232.68 429.12 m 232.68 415.92 l 238.08 415.92 l 238.08 428.16 l 322.32 428.16 l 322.32 415.92 l 327.72 415.92 l 327.72 429.12 l W* n 0 792.03 612 -792 re W n 1 g 232.68 415.92 95.04 13.2 re f Q 1 g 238.08 415.92 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 418.68 Tm 0 g .0011 Tc .0004 Tw [(2.9)4.9(5)-1( \()4.9(1)-1(.2)4.9(5 t)12.7(o)1.5( )6(6.)8(96)4.9(\))4.9( )]TJ ET q 1 i 327.72 429.12 m 327.72 415.92 l 333.12 415.92 l 333.12 428.16 l 417.3 428.16 l 417.3 415.92 l 422.7 415.92 l 422.7 429.12 l W* n 0 792.03 612 -792 re W n 1 g 327.72 415.92 94.98 13.2 re f Q 1 g 333.12 415.92 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 418.68 Tm 0 g [(4.1)4.9(7)-1( \()4.9(1)-1(.8)4.9(7 t)12.7(o)1.5( )6(9.)8(31)4.9(\))4.9( )]TJ ET q 1 i 422.7 429.12 m 422.7 415.92 l 428.1 415.92 l 428.1 428.16 l 512.82 428.16 l 512.82 415.92 l 518.22 415.92 l 518.22 429.12 l W* n 0 792.03 612 -792 re W n 1 g 422.7 415.92 95.52 13.2 re f Q 1 g 428.1 415.92 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 418.68 Tm 0 g -.0036 Tc .0051 Tw [(3)-5.7(.)-2.7(65)-5.7( \(1)-5.7(.71)-5.7( t)8(o)-3.2( )6(7)-5.8(.)3.3(8)-5.8(0\) )]TJ ET q 1 i 72 415.92 m 72 402.72 l 77.4 402.72 l 77.4 414.96 l 191.16 414.96 l 191.16 402.72 l 196.56 402.72 l 196.56 415.92 l W* n 0 792.03 612 -792 re W n 1 g 72 402.72 124.56 13.2 re f Q 1 g 77.4 402.72 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 405.48 Tm 0 g -.0083 Tc 0 Tw [(CO)-8.7(P)-9(D)-.7( )]TJ ET q 1 i 196.56 415.92 m 196.56 402.72 l 201.96 402.72 l 201.96 414.96 l 227.28 414.96 l 227.28 402.72 l 232.68 402.72 l 232.68 415.92 l W* n 0 792.03 612 -792 re W n 1 g 196.56 402.72 36.12 13.2 re f Q 1 g 201.96 402.72 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 405.48 Tm 0 g .0021 Tc [(22)5.9(20)5.9( )]TJ ET q 1 i 232.68 415.92 m 232.68 402.72 l 238.08 402.72 l 238.08 414.96 l 322.32 414.96 l 322.32 402.72 l 327.72 402.72 l 327.72 415.92 l W* n 0 792.03 612 -792 re W n 1 g 232.68 402.72 95.04 13.2 re f Q 1 g 238.08 402.72 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 405.48 Tm 0 g .0011 Tc .0004 Tw [(4.4)4.9(8)-1( \()4.9(2)-1(.8)4.9(4 t)12.7(o)1.5( )6(7.)8(01)4.9(\))4.9( )]TJ ET q 1 i 327.72 415.92 m 327.72 402.72 l 333.12 402.72 l 333.12 414.96 l 417.3 414.96 l 417.3 402.72 l 422.7 402.72 l 422.7 415.92 l W* n 0 792.03 612 -792 re W n 1 g 327.72 402.72 94.98 13.2 re f Q 1 g 333.12 402.72 84.18 12.24 re f BT 10.02 0 0 10.02 333.12 405.48 Tm 0 g .002 Tc -.0005 Tw [( 7.)8.9(46 )6(\(5.)8.9(0)-.1(6)5.8( t)13.6(o)2.4( )6(10.)8.9(99)5.8(\))5.8( )]TJ ET q 1 i 422.7 415.92 m 422.7 402.72 l 428.1 402.72 l 428.1 414.96 l 512.82 414.96 l 512.82 402.72 l 518.22 402.72 l 518.22 415.92 l W* n 0 792.03 612 -792 re W n 1 g 422.7 402.72 95.52 13.2 re f Q 1 g 428.1 402.72 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 405.48 Tm 0 g -.0036 Tc .0051 Tw [(6)-5.7(.)-2.7(18)-5.7( \(4)-5.7(.30)-5.7( t)8(o)-3.2( )6(8)-5.8(.)3.3(9)-5.8(0\) )]TJ ET q 1 i 72 402.72 m 72 389.52 l 77.4 389.52 l 77.4 401.76 l 191.16 401.76 l 191.16 389.52 l 196.56 389.52 l 196.56 402.72 l W* n 0 792.03 612 -792 re W n 1 g 72 389.52 124.56 13.2 re f Q 1 g 77.4 389.52 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 392.28 Tm 0 g 0 Tc .0015 Tw [(Cer)14.2(e).4(br)14.2(ov)12.1(a)8.6(s)-2.3(c)5.3(u)-2.3(l)6.1(a)2.6(r Disease)6.4( )]TJ ET q 1 i 196.56 402.72 m 196.56 389.52 l 201.96 389.52 l 201.96 401.76 l 227.28 401.76 l 227.28 389.52 l 232.68 389.52 l 232.68 402.72 l W* n 0 792.03 612 -792 re W n 1 g 196.56 389.52 36.12 13.2 re f Q 1 g 201.96 389.52 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 392.28 Tm 0 g .0021 Tc 0 Tw [(15)5.9(04)5.9( )]TJ ET q 1 i 232.68 402.72 m 232.68 389.52 l 238.08 389.52 l 238.08 401.76 l 322.32 401.76 l 322.32 389.52 l 327.72 389.52 l 327.72 402.72 l W* n 0 792.03 612 -792 re W n 1 g 232.68 389.52 95.04 13.2 re f Q 1 g 238.08 389.52 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 392.28 Tm 0 g .0011 Tc .0004 Tw [(4.9)4.9(7)-1( \()4.9(3)-1(.0)4.9(9 t)12.7(o)1.5( )6(7.)8(99)4.9(\))4.9( )]TJ ET q 1 i 327.72 402.72 m 327.72 389.52 l 333.12 389.52 l 333.12 401.76 l 417.3 401.76 l 417.3 389.52 l 422.7 389.52 l 422.7 402.72 l W* n 0 792.03 612 -792 re W n 1 g 327.72 389.52 94.98 13.2 re f Q 1 g 333.12 389.52 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 392.28 Tm 0 g [(6.2)4.9(3)-1( \()4.9(3)-1(.9)4.9(3 t)12.7(o)1.5( )6(9.)8(85)4.9(\))4.9( )]TJ ET q 1 i 422.7 402.72 m 422.7 389.52 l 428.1 389.52 l 428.1 401.76 l 512.82 401.76 l 512.82 389.52 l 518.22 389.52 l 518.22 402.72 l W* n 0 792.03 612 -792 re W n 1 g 422.7 389.52 95.52 13.2 re f Q 1 g 428.1 389.52 84.72 12.24 re f BT 10.02 0 0 10.02 432 392.28 Tm 0 g .0018 Tc -.0003 Tw [( 6.3)5.6(4)-.3( )6(\(4.)8.7(26 t)13.4(o)8.2( 9)5.6(.)2.7(44\))5.6( )]TJ ET q 1 i 72 389.52 m 72 376.32 l 77.4 376.32 l 77.4 388.56 l 191.16 388.56 l 191.16 376.32 l 196.56 376.32 l 196.56 389.52 l W* n 0 792.03 612 -792 re W n 1 g 72 376.32 124.56 13.2 re f Q 1 g 77.4 376.32 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 379.08 Tm 0 g -.0004 Tc .0019 Tw [(Heart F)27.4(a)2.2(ilur)13.8(e)0( )]TJ ET q 1 i 196.56 389.52 m 196.56 376.32 l 201.96 376.32 l 201.96 388.56 l 227.28 388.56 l 227.28 376.32 l 232.68 376.32 l 232.68 389.52 l W* n 0 792.03 612 -792 re W n 1 g 196.56 376.32 36.12 13.2 re f Q 1 g 201.96 376.32 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 204.48 379.08 Tm 0 g .0021 Tc 0 Tw [(14)5.9(27)5.9( )]TJ ET q 1 i 232.68 389.52 m 232.68 376.32 l 238.08 376.32 l 238.08 388.56 l 322.32 388.56 l 322.32 376.32 l 327.72 376.32 l 327.72 389.52 l W* n 0 792.03 612 -792 re W n 1 g 232.68 376.32 95.04 13.2 re f Q 1 g 238.08 376.32 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 379.08 Tm 0 g .0011 Tc .0004 Tw [(3.6)4.9(7)-1( \()4.9(2)-1(.5)4.9(5 t)12.7(o)1.5( )6(5.)8(29)4.9(\))4.9( )]TJ ET q 1 i 327.72 389.52 m 327.72 376.32 l 333.12 376.32 l 333.12 388.56 l 417.3 388.56 l 417.3 376.32 l 422.7 376.32 l 422.7 389.52 l W* n 0 792.03 612 -792 re W n 1 g 327.72 376.32 94.98 13.2 re f Q 1 g 333.12 376.32 84.18 12.24 re f BT 10.02 0 0 10.02 337.92 379.08 Tm 0 g [(3.7)4.9(6)-1( \()4.9(2)-1(.7)4.9(0 t)12.7(o)1.5( )6(5.)8(26)4.9(\))4.9( )]TJ ET q 1 i 422.7 389.52 m 422.7 376.32 l 428.1 376.32 l 428.1 388.56 l 512.82 388.56 l 512.82 376.32 l 518.22 376.32 l 518.22 389.52 l W* n 0 792.03 612 -792 re W n 1 g 422.7 376.32 95.52 13.2 re f Q 1 g 428.1 376.32 84.72 12.24 re f BT 10.02 0 0 10.02 433.2 379.08 Tm 0 g -.0036 Tc .0051 Tw [(4)-5.7(.)-2.7(53)-5.7( \(3)-5.7(.37)-5.7( t)8(o)-3.2( )6(6)-5.8(.)3.3(1)-5.8(1\) )]TJ ET q 1 i 72 376.32 m 72 363.12 l 77.4 363.12 l 77.4 375.36 l 191.16 375.36 l 191.16 363.12 l 196.56 363.12 l 196.56 376.32 l W* n 0 792.03 612 -792 re W n 1 g 72 363.12 124.56 13.2 re f Q 1 g 77.4 363.12 113.76 12.24 re f BT /TT18 1 Tf 10.02 0 0 10.02 77.4 365.88 Tm 0 g .0001 Tc .0014 Tw [(P)17.4(e).5(ripher)26.2(a)2.7(l V)52.5(a)8.7(s)3.8(c)-.6(ular Disea)8.7(s)-2.2(e)6.5( )]TJ ET q 1 i 196.56 376.32 m 196.56 363.12 l 201.96 363.12 l 201.96 375.36 l 227.28 375.36 l 227.28 363.12 l 232.68 363.12 l 232.68 376.32 l W* n 0 792.03 612 -792 re W n 1 g 196.56 363.12 36.12 13.2 re f Q 1 g 201.96 363.12 25.32 12.24 re f BT /TT2 1 Tf 10.02 0 0 10.02 207.06 365.88 Tm 0 g -.0038 Tc 0 Tw [(8)-5.9(76 )]TJ ET q 1 i 232.68 376.32 m 232.68 363.12 l 238.08 363.12 l 238.08 375.36 l 322.32 375.36 l 322.32 363.12 l 327.72 363.12 l 327.72 376.32 l W* n 0 792.03 612 -792 re W n 1 g 232.68 363.12 95.04 13.2 re f Q 1 g 238.08 363.12 84.24 12.24 re f BT 10.02 0 0 10.02 242.88 365.88 Tm 0 g .0011 Tc .0004 Tw [(3.1)4.9(4)-1( \()4.9(1)-1(.7)4.9(0 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TD -.0022 Tc .0037 Tw [(th)-5.2(at class fo)-5.2(r)-4.5( each gr)-4.5(oup)-5.2( )6(o)-5.2(f)-4.5( )6(h)-5.2(ypno)-5.2(tics non)-5.2(u)-5.2(s)-2.3(er)-4.5(s )6(an)-5.2(d user)-4.5(s. )]TJ ET 72 697.74 46.68 .47998 re f BT 10.02 0 0 10.02 72 687.84 Tm -.0016 Tc .0031 Tw [(No)-4.6(te t)6.8(h)-4.6(at th)-4.6(e )6(m)9.8(o)-4.6(re p)-4.6(a)-.9(tien)-4.6(t).8(s )6(were d)-4.6(i).8(ag)-4.6(no)-4.6(sed)-4.6( )6(with)-4.6( th)-4.6(e co)-4.6(m)9.8(o)]TJ 23.2515 0 TD -.0014 Tc .0029 Tw [(rb)-4.4(id)-4.4(ity b)-4.4(e)5.3(fore th)-4.4(e )6(p)-4.4(e)-.7(ri)7(o)-4.4(d)1.6( of )6(ob)-4.4(serv)-4.4(ation)-4.4( )6(\(Sup)-4.4(p)-4.4(l)1(em)10(en)-4.4(tary )]TJ -23.2515 -1.1497 TD .0013 Tc .0002 Tw [(T)73.2(a)2(bl)3.7(e 4)4.3(\))-1(, t)9.7(h)-1.7(e )6(fe)8(wer)5( co)4.3(ul)3.7(d)4.3( be)8( d)4.3(i)3.7(agn)4.3(o)-1.7(se)8(d )6(wi)3.7(t)3.7(h)-1.7( )6(new)4.9( i)3.7(n)-1.7(ci)3.7(de)8(nce)8( )6(du)4.3(ri)3.7(n)4.3(g)-1.7( t)9.7(h)-1.7(e )6(peri)9.7(od)4.3( o)4.3(f)-1( 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)-37.6(Fl)-4.2(ur)22.9(a)-4.3(z)-2.7(.)-5.3( )15.1(B)-5.1(a)-4.3(rbi)-4.2(t)-.9(.)-5.3( )52.7(A)-4.8(n)8.6(ti)-4.2(hi)-4.2(s)6.2(t)-.9(.)-5.3( )-7.5(Mi)-4.2(x)21.7(e)-2(d)-6.4( )]TJ -4.5489 -1.8045 TD .0003 Tc 0 Tw [(As)8.2(th)3.1(ma)-9.8( )]TJ /TT2 1 Tf 7.2256 0 TD -.0031 Tc 2.1154 Tw [(2.)-6.3(2)-7.5( 2.)-6.3(5)-7.5( )-699.2(2.)-6.3(4)-7.5( )-819.5(2.)-6.3(6)-7.5( )-466.1(1.)-6.3(9)-7.5( )-1383.4(0.)-6.3(9)-7.5( )-902.2(3.)-6.3(1)-7.5( )-609(3.)-6.3(8)-7.5( )-654.1(2.)-6.3(2)-7.5( )-1406(1.)-6.3(4)-7.5( )-451.1(3.)-6.3(1)-7.5( )]TJ ET 226.98 611.28 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 97.14 599.1 Tm .0034 Tc 0 Tw [(C)6.4(e)3.1(r)13(e)3.1(br)20.5(ov)17.9(ascu)6.2(lar )]TJ /TT2 1 Tf 10.7444 0 TD -.0031 Tc 2.1154 Tw [(1.)-6.3(8)-7.5( 2.)-6.3(1)-7.5( )-699.2(2.)-6.3(1)-7.5( )-819.5(1.)-6.3(8)-7.5( )-466.1(0.)-6.3(4)-7.5( )-1383.4(1.)-6.3(5)-7.5( )-902.2(3.)-6.3(1)-7.5( )-609(4.)-6.3(5)-7.5( )-654.1(1.)-6.3(8)-7.5( )-1406(3.)-6.3(2)-7.5( )-451.1(2.)-6.3(1)-7.5( )]TJ ET 226.98 596.88 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 85.62 584.7 Tm -.0011 Tc .0006 Tw [(Co)-4.9(r)16(o)-4.9(na)-3.7(r)-6.5(y)-1.2( H)-9.3(e)-1.4(a)-3.7(r)1(t Di)-11.1(s.)-4.7( )]TJ /TT2 1 Tf 12.188 0 TD -.0031 Tc 2.1154 Tw [(3.)-6.3(0)-7.5( 3.)-6.3(1)-7.5( )-699.2(2.)-6.3(6)-7.5( )-819.5(3.)-6.3(5)-7.5( )-466.1(0.)-6.3(0)-7.5( )-1383.4(3.)-6.3(9)-7.5( )-902.2(4.)-6.3(7)-7.5( )-609(3.)-6.3(8)-7.5( )-654.1(3.)-6.3(1)-7.5( )-1406(3.)-6.3(8)-7.5( )-451.1(3.)-6.3(6)-7.5( )]TJ ET 226.98 582.48 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 86.88 570.3 Tm -.001 Tc .0005 Tw [(Ch)-5.7(r)16.1(o)-4.8(ni)-3.5(c)-3.6( Ki)-3.5(d)-5.7(n)1.8(ey Di)-11(s.)-4.6( )]TJ /TT2 1 Tf 12.0301 0 TD -.0031 Tc 2.1154 Tw [(0.)-6.3(6)-7.5( 0.)-6.3(9)-7.5( )-699.2(0.)-6.3(6)-7.5( )-819.5(1.)-6.3(2)-7.5( )-466.1(0.)-6.3(4)-7.5( )-1383.4(1.)-6.3(2)-7.5( )-902.2(3.)-6.3(1)-7.5( )-609(0.)-6.3(8)-7.5( )-654.1(0.)-6.3(9)-7.5( )-1406(1.)-6.3(4)-7.5( )-451.1(1.)-6.3(0)-7.5( )]TJ ET 226.98 568.08 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 131.82 555.9 Tm -.0105 Tc 0 Tw [(CO)-10.9(P)-12.1(D)-19.2( )]TJ /TT2 1 Tf 6.3985 0 TD -.0031 Tc 2.1154 Tw [(2.)-6.3(1)-7.5( 2.)-6.3(7)-7.5( )-699.2(2.)-6.3(0)-7.5( )-819.5(2.)-6.3(6)-7.5( )-466.1(0.)-6.3(4)-7.5( )-1383.4(3.)-6.3(9)-7.5( )-902.2(7.)-6.3(8)-7.5( )-609(6.)-6.3(0)-7.5( )-654.1(3.)-6.3(1)-7.5( )-1406(2.)-6.3(0)-7.5( )-451.1(4.)-6.3(0)-7.5( )]TJ ET 226.98 553.68 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 74.88 541.5 Tm .0007 Tc -.0012 Tw [(Car)10.3(d)3.5(iov)15.2(a)-1.9(scular Disease )]TJ /TT2 1 Tf 13.5338 0 TD -.0031 Tc 2.1154 Tw [(5.)-6.3(1)-7.5( 4.)-6.3(9)-7.5( )-699.2(4.)-6.3(4)-7.5( )-819.5(5.)-6.3(1)-7.5( )-466.1(0.)-6.3(8)-7.5( )-1383.4(5.)-6.3(1)-7.5( )-902.2(6.)-6.3(3)-7.5( )-609(8.)-6.3(3)-7.5( )-654.1(5.)-6.3(7)-7.5( )-1406(4.)-6.3(4)-7.5( )-451.1(5.)-6.3(7)-7.5( )]TJ ET 226.98 539.28 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 118.2 527.1 Tm .0009 Tc 0 Tw [(Demen)11.2(t)1.7(ia)-9.2( )]TJ /TT2 1 Tf 8.1053 0 TD -.0031 Tc 2.1154 Tw [(0.)-6.3(3)-7.5( 0.)-6.3(3)-7.5( )-699.2(0.)-6.3(2)-7.5( )-819.5(0.)-6.3(1)-7.5( )-466.1(0.)-6.3(0)-7.5( )-1383.4(0.)-6.3(3)-7.5( )-902.2(0.)-6.3(0)-7.5( )-609(0.)-6.3(8)-7.5( )-654.1(0.)-6.3(9)-7.5( )-1406(0.)-6.3(4)-7.5( )-451.1(0.)-6.3(4)-7.5( )]TJ ET 226.98 524.88 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 121.62 512.7 Tm .0007 Tc 0 Tw [(Diabe)7.9(t)16.6(es)-6.4( )]TJ /TT2 1 Tf 7.6767 0 TD -.0031 Tc 2.1154 Tw [(4.)-6.3(8)-7.5( 4.)-6.3(0)-7.5( )-699.2(3.)-6.3(8)-7.5( )-819.5(3.)-6.3(9)-7.5( )-466.1(0.)-6.3(4)-7.5( )-1383.4(3.)-6.3(3)-7.5( )-902.2(6.)-6.3(3)-7.5( )-609(5.)-6.3(3)-7.5( )-654.1(3.)-6.3(9)-7.5( )-1406(4.)-6.3(0)-7.5( )-451.1(4.)-6.3(7)-7.5( )]TJ ET 226.98 510.48 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 107.88 498.3 Tm .0008 Tc -.0013 Tw [(Heart F)31.2(a)-1.8(ilu)3.6(r)10.4(e)-7.1( )]TJ /TT2 1 Tf 9.3985 0 TD -.0031 Tc 2.1154 Tw [(1.)-6.3(5)-7.5( 2.)-6.3(0)-7.5( )-699.2(1.)-6.3(7)-7.5( )-819.5(2.)-6.3(4)-7.5( )-466.1(0.)-6.3(0)-7.5( )-1383.4(1.)-6.3(2)-7.5( )-902.2(1.)-6.3(6)-7.5( )-609(4.)-6.3(5)-7.5( )-654.1(1.)-6.3(8)-7.5( )-1406(0.)-6.3(8)-7.5( )-451.1(2.)-6.3(8)-7.5( )]TJ ET 226.98 496.08 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 105.96 483.9 Tm .002 Tc 0 Tw [(Hypert)17.9(e)-5.9(n)4.8(sion )]TJ /TT2 1 Tf 9.1353 0 TD -.0031 Tc 2.1154 Tw [(10.)-6.3(7)-7.5( 7.)-6.3(8)-7.5( )-699.2(7.)-6.3(1)-7.5( )-819.5(7.)-6.3(7)-7.5( )-466.1(3.)-6.3(0)-7.5( )-1383.4(8.)-6.3(5)-7.5( )-398.5(17.)-6.3(2)-7.5( )-609(7.)-6.3(5)-7.5( )-654.1(8.)-6.3(8)-7.5( )-1406(9.)-6.3(5)-7.5( )-451.1(9.)-6.3(1)-7.5( )]TJ ET 226.98 481.68 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 125.28 469.5 Tm -.0001 Tc 0 Tw [(Obesity)-7.7( )]TJ /TT2 1 Tf 7.218 0 TD -.0031 Tc 2.1154 Tw [(2.)-6.3(7)-7.5( 2.)-6.3(5)-7.5( )-699.2(2.)-6.3(2)-7.5( )-819.5(2.)-6.3(1)-7.5( )-466.1(0.)-6.3(4)-7.5( )-1383.4(3.)-6.3(0)-7.5( )-902.2(1.)-6.3(6)-7.5( )-609(1.)-6.3(5)-7.5( )-654.1(3.)-6.3(5)-7.5( )-1406(2.)-6.3(6)-7.5( )-451.1(3.)-6.3(5)-7.5( )]TJ ET 226.98 467.28 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 99.96 455.1 Tm -.0007 Tc .0002 Tw [(R)13.4(e)6.5(fl)-3.2(ux & )-7.5(pe)-8.6(p)9.6(t).1(i)-3.2(c)-10.8( )]TJ /TT2 1 Tf 10.391 0 TD -.0031 Tc 2.1154 Tw [(5.)-6.3(8)-7.5( 7.)-6.3(6)-7.5( )-699.2(6.)-6.3(7)-7.5( )-819.5(7.)-6.3(0)-7.5( )-466.1(2.)-6.3(3)-7.5( )-1383.4(7.)-6.3(9)-7.5( )-398.5(12.)-6.3(5)-7.5( )-105.2(12.)-6.3(0)-7.5( )-654.1(7.)-6.3(9)-7.5( )-1406(7.)-6.3(3)-7.5( )-451.1(9.)-6.3(8)-7.5( )]TJ ET 226.98 452.88 .48001 14.4 re f BT /TT18 1 Tf 7.98 0 0 7.98 72.78 440.7 Tm -.0013 Tc .0008 Tw [(P)12.1(e)-1.6(ri)-3.8(phe)-9.2(r)23.3(a)-3.9(l)-3.8( V)48.7(a)-3.9(sc)-3.9(ul)-3.8(a)-3.9(r).8( Di)-3.8(s.)-4.9( )]TJ /TT2 1 Tf 13.797 0 TD -.0031 Tc 2.1154 Tw [(0.)-6.3(8)-7.5( 0.)-6.3(9)-7.5( )-699.2(0.)-6.3(7)-7.5( )-819.5(0.)-6.3(9)-7.5( )-466.1(0.)-6.3(4)-7.5( )-1383.4(0.)-6.3(3)-7.5( )-902.2(0.)-6.3(0)-7.5( )-609(2.)-6.3(3)-7.5( )-654.1(0.)-6.3(9)-7.5( )-1406(1.)-6.3(2)-7.5( )-451.1(1.)-6.3(5)-7.5( )]TJ ET 226.98 438.48 .48001 14.4 re f BT /TT12 1 Tf 10.02 0 0 10.02 306 429.3 Tm 0 Tc 0 Tw ( )Tj /TT10 1 Tf .2515 0 TD ( )Tj -23.6048 -1.1437 TD .0013 Tc .0002 Tw [( )-3341.3(The i)3.7(m)12.7(pressi)3.7(o)4.3(n)-1.7( )6(fr)5(om)12.7( Sup)4.3(p)-1.7(l)3.7(e)2(m)6.7(e)2(nt)3.7(ary)4.3( )18(T)73.2(a)2(bl)3.7(e )6(5 m)12.7(i)3.7(ght)3.7( be t)9.7(h)-1.7(at)9.7( n)4.3(o)-1.7(n)4.3(u)-1.7(se)8(rs )6(were)8( m)12.7(o)-1.7(re l)3.7(i)3.7(k)-1.7(el)3.7(y)4.3( t)3.7(o)-1.7( )6(be )6(newl)3.7(y)4.3( )]TJ ET 1 i q 1 0 0 1 344.58 416.76 cm 0 0 m 31.68 0 l 31.68 -.48 l 0 -.48 l f Q BT 10.02 0 0 10.02 72 406.32 Tm -.0021 Tc .0036 Tw [(d)-5.1(i).3(agn)-5.1(o).9(sed with certain)-5.1( co)-5.1(m)9.3(o)-5.1(rb)-5.1(id)-5.1(ities th)-5.1(an)-5.1( )6(hyp)-5.1(no)-5.1(tic u)-5.1(s)-2.2(ers )6(du)]TJ 24.0299 0 TD -.001 Tc -.0035 Tw [(ri)7.4(n)-4(g)2( )-6(th)-4(e p)-4(e)-.3(ri)7.4(od)-4(s o)-4(f)2.7( )-6(ob)-4(serv)-4(ati)7.4(o)-4(n. )-6( Ho)-4(wev)-4(e)-.3(r)44.6(,)-2.5( if )-6(we )]TJ -24.0299 -1.1437 TD .0001 Tc .0014 Tw [(consider the )6(num)11.5(ber in each group who )6(ha)6.8(d )6(not )6(bee)6.8(n)-2.9( )6(pre)6.8(v)]TJ 23.1737 0 TD -.0046 Tw [(i)8.5(ously diagnose)6.8(d with )-6(the)6.8( )]TJ 10.4731 0 TD -.0001 Tc .0016 Tw [(com)11.3(o)-3.1(rbidity \(Suppl)8.3(e)-5.4(m)11.3(entary )]TJ -33.6467 -1.1497 TD -.0016 Tc .0031 Tw [(T)70.3(a)-.9(b)-4.6(l).8(e 4 sub)-4.6(t).8(racted)-4.6( fro)-4.6(m)9.8( th)-4.6(e total p)-4.6(a)-.9(rticip)-4.6(an)-4.6(ts\) as t)6.8(h)-4.6(e )6(d)-4.6(e)-.9(no)-4.6(m)9.8(i)-5.2(n)-4.6(a)-.9(to)-4.6(r)44(,)-3.1( th)-4.6(e p)-4.6(e)5.1(rcen)-4.6(ts )6(o)-4.6(f)-3.9( t)6.8(h)-4.6(e )6(remain)-4.6(in)-4.6(g p)-4.6(a)-.9(tien)-4.6(t).8(s )6(d)-4.6(i).8(agn)-4.6(o)1.4(sed )]TJ T* -.0006 Tc .0021 Tw [(with )6(new incidence )6(of each c)6.1(o)]TJ 12.1138 0 TD .0004 Tc .0011 Tw [(m)11.8(o)-2.6(rbidity during t)8.8(h)-2.6(e )6(peri)8.8(ods)6.3( of )6(obse)7.1(r)4.1(vation )]TJ 17.6886 0 TD .0002 Tc .0013 Tw [(we)6.9(re )6(greater in the)6.9( )]TJ 7.7066 0 TD -.0004 Tc -.0041 Tw (group of hypnotics )Tj -37.509 -1.1437 TD -.0002 Tc .0017 Tw [(users)5.7( for m)11.2(o)-3.2(st classes \(S)]TJ 9.8144 0 TD .002 Tc -.0185 Tw [(u)5(ppl)4.4(e)8.7(m)7.4(ent)4.4(a)2.7(ry)5( T)73.9(a)2.7(bl)4.4(e )-12(6\))5.7(.)6.5( )]TJ -9.8144 -1.1497 TD 0 Tc 0 Tw ( )Tj /TT12 1 Tf 4.988 -1.1617 TD -.0003 Tc .0018 Tw [(Supplemen)5(tar)6.4(y)-3.3( )18(T)97.8(a)-3.3(ble )6(6: In)5(c)6.4(i)2.1(dence of c)6.4(o)-3.3(m)6.4(o)-3.3(rbid)]TJ 20.2395 0 TD -.0042 Tw [(ities duri)8.1(n)-1(g the periods)5.6( )-6(of obser)6.4(v)-3.3(ation: )]TJ -11.2695 -1.1437 TD -.0001 Tc .0016 Tw [(Per)18.6(cent )6(of patients not pr)18.6(e)6.6(v)-3.1(i)8.3(o)-3.1(usly di)8.3(agnos)5.8(ed )]TJ /TT18 1 Tf 7.98 0 0 7.98 78.84 312.54 Tm -.0021 Tc .0091 Tw [(R)12(e)-2.4(ma)-4.7(i)-4.6(nde)-10(r Inc)-4.7(i)-4.6(de)-10(nc)-4.7(e )]TJ ET 78.84 311.1 69.78 .71997 re f BT 7.98 0 0 7.98 159.42 312.54 Tm -.0017 Tc 1.2643 Tw [(no)-5.5(nu)-6.4(ser)7.9(s)-8.8( )-37.6(use)-9.6(r)15.4(s)-8.8( )45.1(Z)10.2(o)-5.5(l)-4.2(p)1.1(i)-4.2(d)1.1(.)-5.3( T)87.4(e)-2(ma)-4.3(z.)-5.3( )-82.8(Es)6.2(z)12.3(o)-5.5(p.)-5.3( Za)-4.3(l)-4.2(e)-2(pl)-4.2(o)-5.5(n)1.1( )52.6(T)49.8(r).4(i)-4.2(a)-4.3(z)12.3(o)-5.5(l)-4.2(.)2.2( )-60.2(Fl)-4.2(ur)22.9(a)-4.3(z)-2.7(.)-5.3( )-15.1(B)-5.1(a)-4.3(rbi)-4.2(t)-.9(.)-5.3( )15(A)-4.8(n)8.6(ti)-4.2(hi)-4.2(s)6.2(t)-.9(.)-5.3( )-37.6(Mi)-4.2(x)21.7(e)-2.1(d)-6.4( )]TJ /TT2 1 Tf -4.4586 -1.6541 TD -.003 Tc 3.8296 Tw [(Ast)-6.4(h)-3.9(ma)-5.2( 2.)-6.2(3)-7.4( )1684.3(2.)-6.2(7)-7.4( )992.5(2.)-6.2(6)-7.4( )864.7(2.)-6.2(8)-7.4( )1225.6(2.)-6.2(0)-7.4( )308.3(1.)-6.2(0)-7.4( )789.5(3.)-6.2(5)-7.4( )1097.8(3.)-6.2(9)-7.4( )1030.1(2.)-6.2(3)-7.4( )278.2(1.)-6.2(5)-7.4( )1240.6(3.)-6.2(5)-7.4( )]TJ ET 225.3 297.12 .48 13.2 re f BT 7.98 0 0 7.98 96.18 285.54 Tm -.0024 Tc 3.829 Tw [(Cer)15.4(e)-8.6(br)7.9(o)6.1(v)13.2(a)-4.6(s)-2.3(cul)-6(a)-4.6(r)-7.1( 1.)-5.6(8)-6.8( )1684.3(2.)-5.6(1)-6.8( )992.5(2.)-5.6(2)-6.8( )864.7(1.)-5.6(9)-6.8( )1225.6(0.)-5.6(4)-6.8( )308.3(1.)-5.6(5)-6.8( )789.5(3.)-5.6(2)-6.8( )1097.8(4.)-5.6(7)-6.8( 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to)-4.9(tal group)-4.9( )6(with)-4.9(in)-4.9( t)6.5(h)-4.9(e BMI ran)-4.9(g)-4.9(e)4.8( d)-4.9(e)4.8(fin)-4.9(e)4.8(d)-4.9( as )6(m)]TJ 6.48 0 0 6.48 475.08 558.6 Tm 0 Tc 0 Tw (2)Tj 10.02 0 0 10.02 478.32 554.1 Tm .0023 Tc -.0008 Tw [(/)4.7(kg. )]TJ /TT12 1 Tf -36.9581 -1.1437 TD -.0005 Tc .008 Tw [(Ethnicity %)17.5(:)]TJ /TT10 1 Tf 5.515 0 TD 0 Tc .0015 Tw [( the pe)6.7(rce)6.7(n)-3(tage )6(in each self-re)6.7(ported )]TJ 15 0 TD -.0013 Tc .0028 Tw (ethnicity category \(A)Tj 8.479 0 TD -.0004 Tc .0019 Tw [(s)5.5(i)2(ans, Blacks, a)6.3(n)-3.4(d )]TJ -28.994 -1.1497 TD .0012 Tc -.0057 Tw [(Hi)3.6(spa)7.9(n)-1.8(i)3.6(c)1.9(s were)7.9( )-6(com)12.6(b)-1.8(i)3.6(n)-1.8(ed bec)7.9(a)1.9(use of)4.9( )-6(t)3.6(h)-1.8(e sm)6.6(al)3.6(l)3.6( )-6(num)12.6(bers\))4.9(.)-.3( )-6( )]TJ /TT12 1 Tf 23.4491 0 TD -.0001 Tc -.0044 Tw [(Alcoh)5.2(o)-3.1(l Use %)11.9(:)]TJ /TT10 1 Tf 6.6467 0 TD -.0004 Tc .0019 Tw [( is a si)-4(m)11(p)-3.4(le yes/n)-3.4(o)2.6( )]TJ -30.0958 -1.1497 TD .0006 Tc -.0051 Tw [(self-re)7.3(p)3.6(o)-2.4(rt by)3.6( )-6(t)9(h)-2.4(e patient )-6(w)4.2(h)-2.4(et)9(he)]TJ 12.9701 0 TD .0005 Tc .001 Tw [(r)4.2( the )6(patient )6(dri)8.9(nks)6.4( alco)3.5(hol.)5( )]TJ /TT12 1 Tf 11.4491 0 TD .0017 Tc 0 Tw [(Mi)10.1(xed)7(:)]TJ /TT10 1 Tf 3.0479 0 TD -.0014 Tc .0029 Tw [( are )6(data for )6(p)-4.4(a)-.7(tien)-4.4(t)1(s wh)-4.4(o )]TJ -27.4671 -1.1437 TD -.0003 Tc .0018 Tw [(receive)6.4(d at lea)6.4(s)-.4(t two of the)6.4( hypnotic classes)5.6(.)-1.8( )6(Da)]TJ 19.4012 0 TD -.0006 Tc .0021 Tw [(ta for the )6(9th class)5.3( \(Oth)]TJ 9.4012 0 TD -.001 Tc .0025 Tw [(e)5.7(r)-3.3( )6(hypnotics\) are not )]TJ -28.8024 -1.1497 TD -.0019 Tc .0034 Tw [(listed)-4.9(,)-3.4( as it was pr)-4.2(o)-4.9(s)4(p)-4.9(ectiv)-4.9(ely )6(d)-4.9(ecid)-4.9(e)4.8(d)-4.9( )6(n)-4.9(o)-4.9(t).5( t)6.5(o)-4.9( )6(an)-4.9(alyze d)-4.9(a)-1.2(ta )6(f)-4.2(o)1.1(r)-4.2( th)-4.9(is )6(h)-4.9(ypno)-4.9(tic class b)-4.9(ecau)-4.9(s)-2(e )6(of)-4.2( th)-4.9(e )]TJ T* -.0018 Tc .0033 Tw [(sm)9.6(a)-7.1(ll n)-4.8(u)-4.8(m)9.6(b)-4.8(e)-1.1(r)-4.1(s)-1.9( )6(o)-4.8(f)1.9( pr)-4.1(escr)-4.1(i)6.6(p)-4.8(tio)-4.8(ns and)-4.8( t)6.6(h)-4.8(e inhom)9.6(o)-4.8(g)-4.8(e)-1.1(n)-4.8(e)-1.1(ity o)-4.8(f)-4.1( t)6.6(h)-4.8(eir)-4.1( )6(ph)-4.8(ar)-4.1(m)9.6(aco)-4.8(lo)-4.8(g)-4.8(i).6(c ef)13.8(f)-4.1(ects. )]TJ -3.5928 -1.1437 TD 0 Tc 0 Tw ( )Tj 0 -1.1497 TD ( )Tj 0 -1.1617 TD ( )Tj /TT12 1 Tf 3.5928 0 TD -.0004 Tc .0019 Tw [(Prior)18.3( pr)18.3(e)6.3(v)2.6(alence and incide)6.3(nce of c)6.3(o)-3.4(m)6.3(o)-3.4(rbidities. )]TJ -3.5928 -1.1437 TD 0 Tc 0 Tw ( )Tj 0 -1.1377 TD .0015 Tc [( )6( )]TJ /TT10 1 Tf 1.2515 0 TD -.0009 Tc .0024 Tw [(Befo)-3.9(re th)-3.9(e )6(p)-3.9(e)-.2(ri)7.5(o)-3.9(d)-3.9(s)5( of )6(ob)-3.9(serv)-3.9(ation)-3.9(,)3.6( h)-3.9(y)8.1(p)-3.9(n)2.1(o)-3.9(t)7.5(ic u)-3.9(s)-1(ers )6(w)-3.3(e)-.2(re)]TJ 21.8383 0 TD -.0013 Tc -.0032 Tw [( diag)-4.3(no)-4.3(sed)-4.3( w)-3.7(ith)-4.3( m)10.1(o)-4.3(re )-6(co)-4.3(m)10.1(o)-4.3(rb)-4.3(idities )-6(th)-4.3(an)-4.3( n)-4.3(onusers for )-6(each)-4.3( )]TJ ET 84.54 426.06 27.18 .48001 re f BT 10.02 0 0 10.02 72 416.1 Tm -.0018 Tc .0033 Tw [(o)-4.8(f)1.9( th)-4.8(e co)-4.8(m)9.6(o)-4.8(rb)-4.8(i)6.6(d)-4.8(ities, th)-4.8(at is, before th)-4.8(e first-reco)-4.8(rd)-4.8(ed)-4.8( )6(h)]TJ 21.8982 0 TD .0032 Tw [(ypn)-4.7(otic p)-4.7(r)-4(escrip)-4.7(tion fo)-4.7(r )6(81)-4.7(.5)-4.7(% )6(o)-4.7(f)2( users )6(\(Su)-4.7(p)1.3(p)-4.7(l).7(em)9.7(e)-7(n)-4.7(tary )18(T)70.2(a)-1(b)-4.7(l).7(e )]TJ -21.8982 -1.1437 TD .0002 Tc .0013 Tw [(4\). )18(T)6.2(h)-2.8(e )6(pe)6.9(rcentages for eac)6.9(h )6(com)11.6(o)-2.8(rbidity)]TJ 16.6946 0 TD [( class are)6.9( also list)8.6(e).9(d )6(for )6(users )6(of )]TJ 12.9701 0 TD -.0004 Tc .0019 Tw [(each m)11(e).3(dication class )6(uniquely and for )]TJ -29.6647 -1.1497 TD -.0001 Tc .0016 Tw [(those)6.6( who )6(were prescri)8.3(b)-3.1(ed more)6.6( tha)6.6(n)-3.1( )6(one)6.6( hypnotic class \(m)]TJ 23.9162 0 TD -.0012 Tc .0027 Tw [(ix)-4.2(ed)-4.2(\). )18(Th)-4.2(e esti)-4.8(m)10.2(a)-.5(tes fo)-4.2(r zolp)-4.2(id)-4.2(em)10.2(, te)-6.5(m)10.2(aze)-6.5(p)-4.2(a)-.5(m)10.2(,)-2.7( an)-4.2(d)-4.2( t)7.2(h)-4.2(e )]TJ -23.9162 -1.1437 TD .0016 Tc -.0001 Tw [(m)7(i)4(xed g)4.6(r)5.3(ou)4.6(p m)13(a)2.3(y)4.6( be )6(reaso)4.6(n)-1.4(a)8.3(b)4.6(l)4(y)4.6( st)4(abl)4(e)2.3(, b)4.6(u)-1.4(t)4( e)8.3(s)1.5(t)4(i)-2(m)13(a)2.3(t)4(e)2.3(s for t)10(h)4.6(e l)4(e)2.3(ss f)5.3(r)-.7(eq)4.6(ue)8.3(nt)4(l)4(y)4.6(-pre)8.3(scri)4(be)8.3(d )6(h)4.6(y)4.6(p)-1.4(n)4.6(o)-1.4(t)4(i)4(c)2.3(s ha)8.3(d t)10(o)4.6(o )6(few)5.2( )]TJ 0 -1.1497 TD -.006 Tw [(pat)3.9(i)3.9(e)2.2(nt)3.9(s )-6(i)3.9(n)4.5( )-6(eac)8.2(h gr)5.2(o)4.5(u)-1.5(p)4.5( )-6(t)3.9(o)-1.5( be r)5.2(e)2.2(l)3.9(i)3.9(a)2.2(bl)3.9(e. )]TJ /TT12 1 Tf 0 -1.1617 TD 0 Tc 0 Tw ( )Tj 4.5629 -1.1437 TD -.0001 Tc .0016 Tw [(Supplemen)5.2(tar)6.6(y)-3.1( )18(T)98(a)-3.1(ble )6(4. Pr)18.6(e)6.6(valence)6.6( of c)6.6(o)2.9(morbid)]TJ 20.6946 0 TD -.0003 Tc .0018 Tw [(ities)5.6( pr)6.4(ior)18.4( to )6(the )6(peri)]TJ 8.7904 0 TD .0001 Tc -.0046 Tw [(ods of obser)6.8(v)-2.9(ation)5.4(:)3.8( )]TJ -17.1317 -1.1497 TD .0006 Tc .0009 Tw [(Per)19.3(cents)6.5( o)3.6(f)-1.7( p)5.9(a)3.6(tients)6.5( dia)3.6(g)-2.4(n)5.9(o)-2.4(s)6.5(e)1.3(d )]TJ 6.4371 -1.1497 TD 0 Tc 0 Tw ( )Tj -22.4192 -1.3174 TD -.0014 Tc -.0031 Tw [(Prio)-4.4(r)17.3( Co)-4.4(mo)-4.4(rbidities )-6( )]TJ ET 106.44 308.76 61.14 .96002 re f BT /TT18 1 Tf 7.98 0 0 7.98 178.32 310.8 Tm -.0017 Tc 1.129 Tw [(no)-5.5(nu)-6.4(ser)7.9(s)-8.8( use)-9.6(r)15.4(s)-8.8( Z)10.2(o)-5.5(l)-4.2(p)1.1(i)-4.2(d)1.1(.)-5.3( )-7.5(T)87.4(e)-2(ma)-4.3(z.)-5.3( Es)6.2(z)12.3(o)-5.5(p.)-5.3( )-7.5(Za)-4.3(l)-4.2(e)-2(pl)-4.2(.)-5.3( T)49.8(r).4(i)-4.2(a)-4.3(z)12.3(o)-5.5(l)-4.2(.)2.2( )-7.5(Fl)-4.2(ur)22.9(a)-4.3(z)-2.7(.)-5.3( )-7.5(B)-5.1(a)-4.3(rbi)-4.2(t)-.9(.)-5.3( A)-4.8(n)8.6(ti)-4.2(hi)-4.2(s)6.2(t)-.9(.)-5.3( Mi)-4.2(x)21.7(e)-2(d)-6.4( )]TJ /TT12 1 Tf 10.02 0 0 10.02 134.22 297.0001 Tm .0003 Tc 0 Tw [(Ast)4(h)-.4(ma)3.3( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 297.0001 Tm -.0031 Tc 2.0477 Tw [(4.)-6.3(4)-7.5( 8.)-6.3(8)-7.5( )-654.1(8.)-6.3(5)-7.5( )-714.3(8.)-6.3(7)-7.5( )-421.1(7.)-6.3(9)-7.5( )-82.7(10.)-6.3(3)-7.5( )-293.2(10.)-6.3(9)-7.5( )-556.4(3.)-6.3(0)-7.5( )-624.1(6.)-6.3(1)-7.5( )-1330.8(5.)-6.3(7)-7.5( )82.7(10.)-6.3(0)-7.5( )]TJ ET 242.1 294.84 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 96.3 283.2 Tm .0011 Tc 0 Tw [(Cer)19.8(e)1.8(br)25.8(ov)4.1(asc)7.8(u)6.4(l)3.5(a)-1.9(r )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 283.2 Tm -.0031 Tc 2.4688 Tw [(2.)-6.3(0)-7.5( )421.1(4.)-6.3(1)-7.5( )-233(3.)-6.3(8)-7.5( )-293.2(4.)-6.3(2)-7.5( 1.)-6.3(5)-7.5( )-165.4(2.)-6.3(1)-7.5( )-375.9(3.)-6.3(1)-7.5( )-135.3(3.)-6.3(0)-7.5( )-203(6.)-6.3(1)-7.5( )-909.7(6.)-6.3(5)-7.5( 4.)-6.3(8)-7.5( )]TJ ET 242.1 281.04 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 79.74 269.4001 Tm .0012 Tc .0003 Tw [(Cor)25.9(o)-1.8(n)6.5(a)-1.8(r)7.9(y)-1.8( He)7.9(a)4.2(r)1.9(t )6(Dis.)5.7( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 269.4001 Tm -.0031 Tc 1.5439 Tw [(6.)-6.3(3)-7.5( 11.)-6.3(4)-7.5( )-654.2(11.)-6.3(5)-7.5( )-714.3(12.)-6.3(4)-7.5( )-924.9(9.)-6.3(0)-7.5( )-1090.3(8.)-6.3(2)-7.5( )-797(15.)-6.3(6)-7.5( )-556.4(10.)-6.3(5)-7.5( )-1127.9(4.)-6.3(8)-7.5( )-1330.9(10.)-6.3(1)-7.5( )-421.1(12.)-6.3(2)-7.5( )]TJ ET 242.1 267.24 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 80.28 255.6001 Tm .0003 Tc .0012 Tw [(Chr)25(o)-2.7(nic Kid)5.6(n)5.6(e)1(y )6(Dis.)4.8( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 255.6001 Tm -.0031 Tc 2.4688 Tw [(0.)-6.3(3)-7.5( )421.1(0.)-6.3(8)-7.5( )-233(0.)-6.3(9)-7.5( )-293.2(0.)-6.3(7)-7.5( 0.)-6.3(0)-7.5( )-165.4(1.)-6.3(2)-7.5( )-375.9(1.)-6.3(6)-7.5( )-135.3(1.)-6.3(5)-7.5( )-203(0.)-6.3(9)-7.5( )-909.7(0.)-6.3(8)-7.5( 0.)-6.3(9)-7.5( )]TJ ET 242.1 253.44 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 139.26 241.8 Tm .0015 Tc 0 Tw [(COP)7.6(D)5.1( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 241.8 Tm -.0031 Tc 2.4688 Tw [(3.)-6.3(4)-7.5( )421.1(6.)-6.3(4)-7.5( )-233(6.)-6.3(7)-7.5( )-293.2(6.)-6.3(3)-7.5( 7.)-6.3(1)-7.5( )-165.4(6.)-6.3(6)-7.5( )-375.9(6.)-6.3(3)-7.5( )-135.3(5.)-6.3(3)-7.5( )-203(3.)-6.3(9)-7.5( )-909.7(4.)-6.3(6)-7.5( 6.)-6.3(6)-7.5( )]TJ ET 242.1 239.64 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 101.64 230.3401 Tm .0018 Tc 0 Tw [(Car)8.5(d)1.1(i)4.2(o)4.8(va)4.8(scul)10.2(ar)20.5( )]TJ 3.4192 -1.1497 TD .0004 Tc [(Disease)7.1( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 218.8201 Tm -.0031 Tc 1.965 Tw [(9.)-6.3(0)-7.5( )421.1(16.)-6.3(5)-7.5( )-233.1(16.)-6.3(6)-7.5( )-293.2(17.)-6.3(1)-7.5( 10.)-6.3(9)-7.5( )-165.4(11.)-6.3(2)-7.5( )-375.9(20.)-6.3(3)-7.5( )-135.3(15.)-6.3(0)-7.5( )-203(11.)-6.3(0)-7.5( )-909.8(16.)-6.3(8)-7.5( 17.)-6.3(9)-7.5( )]TJ ET 242.1 216.6 .48001 23.04 re f BT /TT12 1 Tf 10.02 0 0 10.02 126.48 205.0201 Tm -.0012 Tc 0 Tw (Dementia )Tj /TT2 1 Tf 7.98 0 0 7.98 198.54 205.0201 Tm -.0031 Tc 2.4688 Tw [(0.)-6.3(3)-7.5( )421.1(0.)-6.3(4)-7.5( )-233(0.)-6.3(5)-7.5( )-293.2(0.)-6.3(1)-7.5( 0.)-6.3(4)-7.5( )-165.4(0.)-6.3(3)-7.5( )-375.9(0.)-6.3(0)-7.5( )-135.3(0.)-6.3(0)-7.5( )-203(0.)-6.3(4)-7.5( )-909.7(1.)-6.3(0)-7.5( 0.)-6.3(2)-7.5( )]TJ ET 242.1 202.8 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 130.92 191.22 Tm .0004 Tc 0 Tw [(Diabe)7.1(t)-1.9(es)6.3( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 191.22 Tm -.0031 Tc 1.5439 Tw [(9.)-6.3(8)-7.5( 13.)-6.3(9)-7.5( )-654.2(14.)-6.3(0)-7.5( )-714.3(14.)-6.3(6)-7.5( )-924.9(7.)-6.3(9)-7.5( )-586.5(10.)-6.3(9)-7.5( )-797(20.)-6.3(3)-7.5( )-556.4(11.)-6.3(3)-7.5( )-1127.9(9.)-6.3(2)-7.5( )-1330.9(13.)-6.3(9)-7.5( )-421.1(14.)-6.3(8)-7.5( )]TJ ET 242.1 189 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 109.2 177.42 Tm -.0013 Tc .0028 Tw [(Hea)-4.3(r)5.4(t Fa)-4.3(ilur)17.4(e)5.4( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 177.42 Tm -.0031 Tc 2.4688 Tw [(1.)-6.3(7)-7.5( )421.1(4.)-6.3(6)-7.5( )-233(4.)-6.3(9)-7.5( )-293.2(4.)-6.3(2)-7.5( 2.)-6.3(6)-7.5( )-165.4(2.)-6.3(4)-7.5( )127.9(10.)-6.3(9)-7.5( )-135.3(5.)-6.3(3)-7.5( )-203(1.)-6.3(3)-7.5( )-909.7(5.)-6.3(1)-7.5( 4.)-6.3(9)-7.5( )]TJ ET 242.1 175.2 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 109.8 163.6201 Tm .001 Tc 0 Tw [(Hyper)7.7(t)-1.3(ensi)9.4(on)6.3( )]TJ /TT2 1 Tf 7.98 0 0 7.98 194.52 163.6201 Tm -.0031 Tc 1.965 Tw [(26.)-6.3(8)-7.5( )421.1(35.)-6.3(0)-7.5( )-233.1(34.)-6.3(8)-7.5( )-293.2(36.)-6.3(2)-7.5( 33.)-6.3(8)-7.5( )-165.4(27.)-6.3(5)-7.5( )-375.9(37.)-6.3(5)-7.5( )-135.3(36.)-6.3(1)-7.5( )-203(23.)-6.3(7)-7.5( )-909.8(34.)-6.3(5)-7.5( 36.)-6.3(5)-7.5( )]TJ ET 242.1 161.4 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 134.82 149.8201 Tm -.0014 Tc 0 Tw (Obesity )Tj /TT2 1 Tf 7.98 0 0 7.98 198.54 149.8201 Tm -.0031 Tc 2.4688 Tw [(4.)-6.3(0)-7.5( )421.1(8.)-6.3(0)-7.5( )-233(7.)-6.3(4)-7.5( )-293.2(7.)-6.3(9)-7.5( 9.)-6.3(0)-7.5( )-165.4(8.)-6.3(8)-7.5( )-375.9(6.)-6.3(3)-7.5( )-135.3(9.)-6.3(0)-7.5( )-203(4.)-6.3(8)-7.5( )-909.7(8.)-6.3(1)-7.5( 9.)-6.3(1)-7.5( )]TJ ET 242.1 147.6 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 99.84 136.0201 Tm -.0045 Tc .006 Tw [(R)-6.9(e)-3.8(f)-6.8(l)-2.1(ux)-7.5( & p)-5.2(e)-3.8(ptic )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 136.0201 Tm -.0031 Tc 1.965 Tw [(9.)-6.3(2)-7.5( )421.1(20.)-6.3(3)-7.5( )-233.1(20.)-6.3(2)-7.5( )-293.2(19.)-6.3(3)-7.5( 22.)-6.3(9)-7.5( )-165.4(19.)-6.3(3)-7.5( )-375.9(23.)-6.3(4)-7.5( )-135.3(18.)-6.3(8)-7.5( )-706.8(9.)-6.3(2)-7.5( )-909.8(17.)-6.3(2)-7.5( 22.)-6.3(7)-7.5( )]TJ ET 242.1 133.8 .48001 13.8 re f BT /TT12 1 Tf 10.02 0 0 10.02 82.44 124.5001 Tm -.0001 Tc -.0224 Tw [(Peripheral V)93.3(a)2.9(scular)18.6( )]TJ 6.8623 -1.1437 TD .0001 Tc 0 Tw [(Dis.)4.6( )]TJ /TT2 1 Tf 7.98 0 0 7.98 198.54 113.04 Tm -.0031 Tc 2.4688 Tw [(1.)-6.3(3)-7.5( )421.1(3.)-6.3(0)-7.5( )-233(3.)-6.3(3)-7.5( )-293.2(2.)-6.3(8)-7.5( 0.)-6.3(8)-7.5( )-165.4(2.)-6.3(1)-7.5( )-375.9(1.)-6.3(6)-7.5( )-135.3(3.)-6.3(8)-7.5( )-203(1.)-6.3(3)-7.5( )-909.7(3.)-6.3(2)-7.5( 3.)-6.3(0)-7.5( )]TJ ET 242.1 110.82 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[(wi)4.1(del)4.1(y)4.7(-)5.4(d)-1.3(i)4.1(s)1.6(pa)8.4(ra)8.4(t)4.1(e)2.4( pha)8.4(rm)13.1(acol)4.1(ogy)70.6(. )18(T)7.7(h)4.7(us,)6.2( C)4(l)4.1(ass 9)4.7(\))-.6( )6(was )6(defi)10.1(ne)]TJ 23.5569 0 TD -.0063 Tw [(d onl)4.2(y)4.8( )-6(t)4.2(o)4.8( )-6(kee)8.5(p)-1.2( t)4.2(h)-1.2(ese )-6(ra)8.5(rel)4.2(y)4.8(-p)4.8(r)5.5(e)2.5(scri)4.2(be)8.5(d dr)5.5(u)4.8(g)-1.2(s fr)5.5(om)13.2( )-6(bei)4.2(ng )]TJ -23.5569 -1.1437 TD .0002 Tc .0013 Tw [(confounded wi)8.6(th the )6(othe)6.9(r cla)6.9(sses of )]TJ 14.8623 0 TD -.0001 Tc .0016 Tw [(m)11.3(e).6(dication. For eac)6.6(h )6(class of m)11.3(e).6(dica)]TJ 15.0359 0 TD -.0019 Tc .0034 Tw [(tio)-4.9(n)-4.9(,)-3.4( t)6.5(h)-4.9(e )6(nu)-4.9(mb)-4.9(er)-4.2(s of)-4.2( )6(un)-4.9(it doses \()-4.2(e)4.8(.g., )]TJ -29.8982 -1.1497 TD -.0026 Tw [(p)-4.9(ills\) )-6(prescrib)-4.9(ed)-4.9( \(in)-4.9(c)-1.2(lud)-4.9(i).5(ng)-4.9( )-6(t)6.5(h)1.1(o)-4.9(s)-2(e p)-4.9(r)-4.2(escrib)-4.9(ed)-4.9( th)-4.9(ro)-4.9(ugh)-4.9( )-6(re)]TJ 21.9521 0 TD -.0016 Tc .0031 Tw [(fills\) were su)-4.6(mmed)-4.6( for each)-4.6( )6(p)-4.6(a)-.9(tient u)-4.6(p)1.4( to)-4.6( t)6.8(h)-4.6(e end)-4.6( )6(o)-4.6(f)2.1( th)-4.6(e )]TJ -21.9521 -1.1497 TD .0013 Tc .0002 Tw [(peri)9.7(od)4.3( o)4.3(f)-1( )6(ob)4.3(ser)5(v)-1.7(at)3.7(i)3.7(o)-1.7(n)4.3( \()5(d)-1.7(efi)9.7(n)-1.7(e)8(d)4.3( ab)4.3(ove)8(\).)5.8( )18(T)7.3(h)-1.7(e )6(n)4.3(u)-1.7(m)12.7(b)-1.7(er o)4.3(f)-1( )]TJ 21.982 0 TD .0001 Tc .0014 Tw [(unit )6(dos)6(es )6(presc)6.8(r)-2.2(ibe)6.8(d)-2.9( )6(for that class)6( )6(was m)11.5(e).8(r)15.7(g)-2.9(ed int)8.5(o)-2.9( the)6.8( )]TJ -21.982 -1.1437 TD -.0007 Tc .0022 Tw [(master file. )6( )]TJ 0 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1557 TD ( )Tj /TT12 1 Tf 3.5928 0 TD -.0015 Tc .003 Tw [(Statistica)-4.5(l models. )6( )]TJ -3.5928 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1377 TD ( )Tj /TT10 1 Tf 3.5928 0 TD -.0007 Tc .0022 Tw [(Cox proportional hazards m)10.7(o)-3.7(dels \(S)]TJ 14.4192 0 TD -.0003 Tc -.0042 Tw [(PSS 12.0.0 for )18(W)33.4(i)8.1(ndows\) were)6.4( )-6(co)]TJ 13.5509 0 TD .0018 Tw [(m)11.1(p)-3.3(uted using )6(backwards ste)6.4(p)2.7(wise )]TJ -31.5629 -1.1437 TD -.0028 Tc .0043 Tw [(eli)-6.4(m)2.6(in)-5.8(atio)-5.8(n)-5.8( sp)-5.8(ecifyin)-5.8(g)-5.8( all co)-5.8(va)]TJ 12.3353 0 TD -.0004 Tc .0019 Tw [(riates with )6(cri)8(t)2(eria of p )]TJ /TT9 1 Tf 9.3413 0 TD 0 Tc 0 Tw <0094>Tj /TT10 1 Tf .5449 0 TD -.0015 Tc .003 Tw [( 0.10)-4.5( to retain, an)-4.5(d p)-4.5( )]TJ /TT9 1 Tf 8.485 0 TD 0 Tc 0 Tw <0094>Tj /TT10 1 Tf .5509 0 TD -.0011 Tc .0026 Tw [( )6(0.05 to re)5.6(-enter)50.5(. )18(T)5(h)-4.1(e t)7.3(w)-3.5(o control )]TJ -31.2575 -1.1497 TD .0001 Tc .0014 Tw [(nonusers)6( m)11.5(a).8(tc)-5.2(hed to eac)6.8(h )6(use)6.8(r)-2.2( were a)6.8(ssigne)6.8(d)-2.9( the)6.8( sam)11.5(e).8( star)]TJ 23.5269 0 TD -.0015 Tc .003 Tw [(t o)-4.5(f)2.2( th)-4.5(eir )6(p)-4.5(e)5.2(riod)-4.5( )6(o)-4.5(f)2.2( ob)-4.5(serv)-4.5(ation)-4.5( as th)-4.5(e )6(u)-4.5(s)-1.6(er )6(un)-4.5(less th)-4.5(at )]TJ -23.5269 -1.1497 TD -.0025 Tc .004 Tw [(r)-4.8(e)-1.8(su)-5.5(lted in)-5.5( a )6(p)-5.5(e)4.2(r)-4.8(i)-.1(od)-5.5( )6(o)-5.5(f)-4.8( )6(ob)-5.5(serv)-5.5(atio)-5.5(n)-5.5( <0)-5.5(.2)-5.5(3 year fo)-5.5(r)-4.8( t)5.9(h)-5.5(e co)-5.5(n)-5.5(t)5.9(r)-4.8(o)-5.5(l)5.9( no)-5.5(nu)-5.5(ser)43.1(,)-4( in which)-5.5( r)-4.8(a)4.2(r)-4.8(e)-1.8( instan)-5.5(ces, Jan)-5.5(u)-5.5(a)4.2(r)-4.8(y).5( )6(1)-5.5( )6(20)-5.5(02)-5.5( )6(or)-4.8( th)-5.5(e )]TJ 0 -1.1437 TD -.0012 Tc .0027 Tw [(first record)-4.2(ed)-4.2( )6(visit th)-4.2(ereafter )6(was selected to start th)-4.2(e )6(p)-4.2(e)]TJ 22.3054 0 TD -.0015 Tc .003 Tw [(riod)-4.5( )6(o)-4.5(f)2.2( ob)-4.5(serv)-4.5(ation)-4.5( )6(for th)-4.5(is con)-4.5(t).9(ro)-4.5(l non)-4.5(user)56.1(. )18(Thu)-4.5(s)-1.6(, t)6.9(h)-4.5(e )]TJ -22.3054 -1.1497 TD .0017 Tc -.0002 Tw [(pr)5.4(o)4.7(p)-1.3(o)4.7(r)-.6(t)4.1(i)4.1(onal)4.1( )6(ha)8.4(zards)7.6( m)13.1(odel)4.1(s)1.6( c)8.4(ove)8.4(re)8.4(d i)4.1(n)-1.3(t)4.1(e)2.4(r)5.4(v)-1.3(al)10.1(s st)4.1(art)4.1(i)4.1(n)4.7(g )6(wi)4.1(t)4.1(h)-1.3( )6(t)4.1(h)-1.3(e fi)4.1(r)5.4(s)1.6(t)4.1( hy)10.7(pn)4.7(ot)10.1(i)4.1(c)2.4( presc)8.4(r)-.6(i)4.1(p)-1.3(t)4.1(i)4.1(o)4.7(n )6(aft)4.1(e)2.4(r Ja)8.4(n)4.7(u)-1.3(ary)4.7( )6(1)4.7(,).2( 2)4.7(0)4.7(0)-1.3(2)4.7( f)5.4(o)-1.3(r)5.4( )]TJ T* -.0013 Tc .0028 Tw [(u)-4.3(s)-1.4(ers \(and)-4.3( )6(for )6(al)-4.9(m)10.1(o)-4.3(st all co)-4.3(n)-4.3(t)7.1(ro)-4.3(l )6(no)-4.3(nu)-4.3(sers match)-4.3(e)-.6(d)-4.3( t)7.1(o)-4.3( eac)]TJ 22.7545 0 TD -.0016 Tc .0031 Tw [(h)-4.6( )6(u)-4.6(s)-1.7(er\) and)-4.6( ex)-4.6(tend)-4.6(ed un)-4.6(til d)-4.6(eat)6.8(h, a lost-to-fo)-4.6(llow-u)-4.6(p)1.4( date, )]TJ -22.7545 -1.1437 TD .0001 Tc .0014 Tw [(or Decem)11.5(ber )6(31, )6(2006. Beca)6.8(use it )6(was )6(recognize)6.8(d that)8.5( m)11.5(a)-5.2(ny )]TJ 24.6946 0 TD 0 Tc .0015 Tw [(deat)8.4(hs )6(occ)6.7(u)3(rre)6.7(d in the )6(first)8.4( m)11.4(onth after the final clinic )]TJ -24.6946 -1.1497 TD -.0003 Tc .0018 Tw [(visit which )6(ha)6.4(d ended the )6(pe)6.4(riod of )6(obse)]TJ 16.1617 0 TD -.0005 Tc .002 Tw [(rvation, e)6.2(v)-3.5(ide)6.2(n)-3.5(tly because m)10.9(a).2(ny patients )]TJ 16.515 0 TD -.0002 Tc .0017 Tw [(could )6(not be)6.5( see)6.5(n)-3.2( in the clinic in )]TJ -32.6766 -1.1497 TD .0006 Tc .0009 Tw [(their term)12(inal m)12(onths and m)12(a)1.3(y have)7.3( recei)9(ve)7.3(d ca)7.3(re at )6(hom)12(e, )]TJ 23.8563 0 TD .0001 Tc .0014 Tw [(in the)6.8( hos)6(p)-2.9(ital, or i)8.5(n)-2.9( )6(hos)6(pice,)]TJ 11.5569 0 TD 0 Tc .0015 Tw [( deaths )6(occurri)8.4(ng in t)8.4(h)-3(is )]TJ -35.4132 -1.1437 TD .0015 Tc 0 Tw [(fi)3.9(rst)3.9( m)12.9(ont)3.9(h )6(fol)3.9(l)9.9(owi)9.9(n)-1.5(g)4.5( t)3.9(h)-1.5(e )6(pe)8.2(ri)3.9(od)4.5( o)4.5(f)-.8( )6(o)4.5(b)-1.5(ser)5.2(v)-1.5(at)3.9(i)3.9(o)-1.5(n)4.5( we)8.2(re i)9.9(n)-1.5(cl)3.9(u)4.5(d)4.5(e)2.2(d as)7.4( o)4.5(u)-1.5(t)3.9(c)2.2(om)12.9(e event)3.9(s)7.4( i)3.9(n)-1.5( t)9.9(h)-1.5(e m)6.9(odel)3.9(s)7.4(. M)4.4(e)8.2(di)3.9(cat)3.9(i)3.9(on )]TJ 0 -1.1497 TD .0017 Tc -.0002 Tw [(presc)8.4(r)-.6(i)4.1(p)-1.3(t)4.1(i)4.1(o)4.7(ns )6(o)4.7(r)-.6(de)8.4(red)4.7( i)4.1(n)-1.3( a)8.4( t)4.1(e)2.4(r)5.4(m)7.1(i)4.1(n)-1.3(al)4.1( )-6(m)13.1(ont)4.1(h a)8.4(f)5.4(t)4.1(e)2.4(r t)4.1(h)-1.3(e e)8.4(n)4.7(d )6(of t)10.1(h)-1.3(e )6(defi)10.1(ned)4.7( pe)8.4(ri)10.1(od)4.7( o)4.7(f)-.6( )6(o)4.7(b)-1.3(ser)5.4(v)-1.3(at)4.1(i)4.1(o)-1.3(n)4.7( we)8.4(re )6(n)4.7(o)-1.3(t)4.1( i)4.1(n)4.7(cl)4.1(ude)8.4(d i)4.1(n)4.7( t)4.1(h)-1.3(e)8.4( )]TJ T* -.0014 Tc .0029 Tw [(m)10(o)-4.4(d)-4.4(e)-.7(ls. Fo)-4.4(r t)7(h)1.6(e co)-4.4(m)10(o)-4.4(rb)-4.4(i)7(d)-4.4(ities listed)-4.4( in)-4.4( )6(Supple)-6.7(m)10(en)-4.4(tary )18(T)70.5(a)-.7(b)-4.4(l)1(e 2)-4.4(,)3.1( strata )6(w)-3.8(e)-.7(re con)-4.4(s)-1.5(tru)-4.4(c)-.7(ted)-4.4( )6(of p)-4.4(a)-.7(tien)-4.4(t)1(s )6(\(bo)-4.4(t)7(h)-4.4( )6(u)-4.4(s)-1.5(ers an)-4.4(d )]TJ 0 -1.1437 TD -.0012 Tc .0027 Tw [(n)-4.2(onu)-4.2(sers\) )6(with no)-4.2( co)-4.2(m)10.2(o)-4.2(rb)-4.2(id)-4.2(it)7.2(ies \(th)-4.2(e)-.5( lar)14.4(g)-4.2(est )6(categ)-4.2(ory\), )6(w)]TJ 22.8204 0 TD [(ith an)-4.3(y )6(o)-4.3(n)-4.3(e)5.4( of t)7.1(h)-4.3(e 12)-4.3( sep)-4.3(a)-.6(rate com)10.1(o)-4.3(rb)-4.3(id)-4.3(ity classes \(th)-4.3(e)5.4( )]TJ -22.8204 -1.1497 TD .0017 Tc -.0002 Tw [(cardi)10.1(ovasc)8.4(ul)4.1(ar)5.4( )6(di)4.1(sease s)7.6(u)4.7(perc)8.4(at)4.1(ego)4.7(r)-.6(y)4.7( w)5.3(o)4.7(ul)4.1(d )6(have)8.4( bee)8.4(n)-1.3( )6(re)8.4(du)4.7(nda)8.4(nt)4.1(\))5.4(,).2( a)8.4(n)-1.3(d)4.7( wi)4.1(t)10.1(h)-1.3( eac)8.4(h )6(uni)10.1(que)8.4( )6(com)13.1(b)-1.3(i)4.1(n)-1.3(at)4.1(i)4.1(on )6(of)5.4( m)13.1(u)-1.3(l)4.1(t)-1.9(i)4.1(p)-1.3(l)4.1(e)2.4( )]TJ T* -.0018 Tc .0033 Tw [(co)-4.8(m)9.6(o)-4.8(r)-4.1(b)-4.8(id)-4.8(ity classes. )24(Th)-4.8(is yield)-4.8(e)-1.1(d)-4.8( )6(1)37.1(1)1.2(6)-4.8( )6(u)-4.8(s)-1.9(ab)-4.8(l)6.6(e)-1.1( str)-4.1(a)-1.1(ta fo)-4.8(r th)-4.8(e )6(main)-4.8( )-6(m)9.6(o)-4.8(d)-4.8(e)-1.1(l, m)9.6(a)-1.1(tch)-4.8(i).6(n)-4.8(g)1.2( alm)9.6(o)-4.8(st all th)-4.8(e h)-4.8(ypno)-4.8(tic u)-4.8(s)-1.9(er)-4.1( co)-4.8(hor)-4.1(t )]TJ 0 -1.1437 TD -.0016 Tc .0031 Tw [(with)-4.6( )6(n)-4.6(onu)-4.6(sers )6(d)-4.6(i).8(agn)-4.6(o)1.4(sed with ex)-4.6(actly th)-4.6(e same co)-4.6(m)9.8(b)-4.6(in)]TJ 22.0359 0 TD -.0017 Tc [(atio)-4.7(n)-4.7(s)-1.8( )6(o)-4.7(f)2( th)-4.7(e )6(12)-4.7( classes of co)-4.7(m)9.7(o)-4.7(rbid)-4.7(ity)67.2(. Infrequ)-4.7(en)-4.7(t )]TJ -22.0359 -1.1497 TD -.0019 Tc .0034 Tw [(co)-4.9(m)9.5(b)-4.9(in)-4.9(atio)-4.9(n)-4.9(s)-2( )6(of sev)-4.9(e)-1.2(ral co)-4.9(m)9.5(o)-4.9(rb)-4.9(i)6.5(d)-4.9(ities with)-4.9( )6(fewer th)-4.9(an)-4.9( )6(5)-4.9( )]TJ 22.7784 0 TD -.0018 Tc .0033 Tw [(u)-4.8(s)4.1(ers an)-4.8(d 5 non)-4.8(users )6(o)-4.8(r)1.9( withou)-4.8(t a sing)-4.8(le )6(o)-4.8(u)-4.8(t).6(come ev)-4.8(en)-4.8(t )]TJ -22.7784 -1.1437 TD .0013 Tc .0002 Tw [(bef)5(o)-1.7(re)8( cen)4.3(so)4.3(ri)3.7(ng)4.3( \(i)3.7(.e)8(., )6(deat)3.7(h)4.3(\))-1( )6(were)8( com)12.7(b)-1.7(i)3.7(n)-1.7(ed)4.3( i)3.7(n)-1.7(t)3.7(o)-1.7( l)3.7(a)8(r)16.9(g)-1.7(e)8(r)-1( st)9.7(ra)8(t)3.7(a)2( defi)9.7(ned)4.3( by)4.3( t)9.7(h)-1.7(e )6(num)12.7(ber )6(of)5( c)8(o)-1.7(m)12.7(o)-1.7(rbi)3.7(d)-1.7(i)3.7(t)3.7(y)4.3( cl)3.7(asses f)5(r)-1(om)12.7( 2 )]TJ 0 -1.1497 TD -.0024 Tc 0 Tw [(to)-5.4( )]TJ /TT9 1 Tf 1.0299 0 TD 0 Tc <0095>Tj /TT10 1 Tf .5449 0 TD .0015 Tw [(7, to a)6.7(v)3(oid )6(creating strata )6(too )6(sm)11.4(all to be)6.7( use)6.7(f)-2.3(ul )6(fo)]TJ 20.0419 0 TD -.0007 Tc .0022 Tw [(r c)6(o)-3.7(mputaton. )18(T)5.4(h)-3.7(e )6(Cox propor)]TJ 12.4072 0 TD -.0005 Tc .002 Tw [(tional hazards m)10.9(o)-3.5(dels were)6.2( )]TJ -34.024 -1.1497 TD -.0001 Tc .0016 Tw [(then c)6.6(o)-3.1(m)11.3(puted as stratified models)5.8(, s)5.8(o)-3.1( that )6(users )6(were)6.6( com)11.3(p)]TJ 24.006 0 TD -.0018 Tc .0033 Tw [(ared)-4.8( )6(with)-4.8( )6(no)-4.8(nu)-4.8(sers of m)9.6(a)-1.1(tch)-4.8(e)-1.1(d)-4.8( co)-4.8(m)9.6(o)-4.8(rb)-4.8(id)-4.8(ity statu)-4.8(s)-1.9( )6(with)-4.8(in )]TJ -24.006 -1.1437 TD 0 Tc .0015 Tw [(each strat)8.4(u)-3(m)11.4( to com)11.4(pute the)6.7( hazard ratios)5.9( )]TJ 16.8802 0 TD -.001 Tc -.0035 Tw [(\(HR\) )-6(ass)4.9(o)-4(ciated with hyp)]TJ 10.1677 0 TD -.0003 Tc -.0042 Tw [(notic use. )-6( )12(T)5.8(h)-3.3(e use of )-6(stratified )-6(m)11.1(odels provi)8.1(ded )]TJ -27.0479 -1.1497 TD .0015 Tc 0 Tw [(m)6.9(a)2.2(t)3.9(c)2.2(hi)3.9(ng )6(o)4.5(n)-1.5( c)8.2(o)-1.5(m)12.9(o)-1.5(rbi)3.9(d)-1.5(i)3.9(t)3.9(y)4.5( st)3.9(at)3.9(us as)7.4( wel)3.9(l)3.9( as)7.4( a)8.2(g)-1.5(e, )6(ge)8.2(nde)8.2(r)41.1(,)0( a)8.2(n)4.5(d)4.5( sm)12.9(oki)3.9(ng)4.5( i)3.9(n)-1.5( t)9.9(h)4.5(e com)12.9(p)-1.5(ari)3.9(s)1.4(o)4.5(n)-1.5(s )6(of)5.2( use)8.2(r)-.8(s a)8.2(n)4.5(d )6(no)4.5(nus)7.4(ers,)6( a)8.2(n)-1.5(d)4.5( )]TJ T* -.0016 Tc .0031 Tw [(also)-4.6( m)9.8(i).8(n)-4.6(i)-5.2(mized)-4.6( th)-4.6(e )6(p)-4.6(o)-4.6(t).8(en)-4.6(tial prob)-4.6(lem)9.8(s)-1.7( o)-4.6(f)-3.9( in)-4.6(teractio)-4.6(n)-4.6(s)4.3( )]TJ 21.5389 0 TD .003 Tw [(and)-4.5( colin)-4.5(earities am)9.9(o)-10.5(n)-4.5(g co)-4.5(m)9.9(o)-4.5(rb)-4.5(id)-4.5(ities. Besi)6.9(d)-4.5(e)-.8(s th)-4.5(i)6.9(s)-1.6(, th)-4.5(e )]TJ -21.5389 -1.1437 TD .0031 Tw [(stratified)-4.6( m)9.8(o)-4.6(d)-4.6(e)5.1(ls were add)-4.6(ition)-4.6(a)-.9(lly ad)-4.6(ju)-4.6(sted)-4.6( )6(for ag)-4.6(e an)-4.6(d th)-4.6(e categ)-4.6(orical risk)-4.6( )6(facto)-4.6(r)2.1(s )6(o)-4.6(f)-3.9( )6(g)-4.6(e)5.1(n)-4.6(d)-4.6(e)5.1(r)38(,)-3.1( sm)9.8(o)-4.6(k)-4.6(i).8(ng)-4.6( )6(statu)-4.6(s)-1.7( \(t)6.8(o)-4.6( )]TJ 0 -1.1497 TD .0004 Tc .0011 Tw [(adjust )6(fo)3.4(r m)11.8(i)2.8(no)3.4(r failu)3.4(res i)8.8(n)-2.6( m)11.8(a)1.1(tching)3.4(\),)4.9( BM)3.3(I, )6(ethnicity)]TJ 21.2994 0 TD -.0001 Tc .0016 Tw [(, m)11.3(a).6(rital status, alc)6.6(o)-3.1(hol use, a)6.6(n)2.9(d )6(pri)8.3(o)-3.1(r cance)6.6(r)51.5(.)4.4( )6( )]TJ -21.2994 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1437 TD -.0014 Tc .0029 Tw [( )-3341.3(Th)-4.4(e i)7(n)-4.4(v)-4.4(e)-.7(sti)7(g)-4.4(ato)-4.4(r)-3.7(s elected)-4.4( t)7(o)-4.4( co)-4.4(n)-4.4(t)7(ro)-4.4(l )6(for co)-4.4(mo)-4.4(rb)-4.4(id)-4.4(ities fi)7(rst )6(record)-4.4(ed)-4.4( )6(b)-4.4(e)5.3(fore or )6(d)-4.4(u)1.6(ring)-4.4( th)-4.4(e )6(p)-4.4(e)-.7(ri)7(o)-4.4(d)-4.4(s)4.5( of )]TJ ET 407.34 226.32 8.34 .48 re f 418.14 226.32 26.16 .48 re f BT 10.02 0 0 10.02 72 216.36 Tm -.0018 Tc .0033 Tw [(o)-4.8(b)-4.8(s)4.1(erv)-4.8(a)-1.1(tio)-4.8(n, in ord)-4.8(e)4.9(r to con)-4.8(t).6(ro)-4.8(l fo)-4.8(r co)-4.8(m)9.6(o)-4.8(rb)-4.8(id)-4.8(ities wh)-4.8(ich)-4.8( m)9.6(i)]TJ 23.5329 0 TD -.002 Tc .0035 Tw [(g)-5(h)-5(t).4( )6(h)-5(a)-1.3(v)-5(e)4.7( cov)-5(e)4.7(rtly led)-5( to)-5( )6(h)-5(ypno)-5(tic prescri)6.4(p)-5(tion)-5(s)-2.1( ev)-5(en)-5( )]TJ -23.5329 -1.1497 TD -.0022 Tc .0037 Tw [(b)-5.2(e)-1.5(fo)-5.2(re th)-5.2(e co)-5.2(m)9.2(o)-5.2(rb)-5.2(id)-5.2(ity was ex)-5.2(p)-5.2(licitly recogn)-5.2(ized)-5.2( and)-5.2( its )]TJ 22.7186 0 TD [(d)-5.2(i).2(ag)-5.2(no)-5.2(sis )6(was reco)-5.2(rd)-5.2(ed)-5.2(. )6( )18(Th)-5.2(is )6(was a h)-5.2(i)6.2(g)-5.2(h)-5.2(l).2(y co)-5.2(n)-5.2(s)3.7(erv)-5.2(a)-1.5(tiv)-5.2(e )]TJ -22.7186 -1.1437 TD -.0005 Tc .002 Tw [(decision to m)10.9(i)-4.1(nimize the ris)5.4(k)2.5( that co)]TJ 14.5269 0 TD -.0016 Tc .0031 Tw [(m)9.8(o)-4.6(rb)-4.6(id)-4.6(i)6.8(ties cau)-4.6(sing)-4.6( )6(h)-4.6(y)1.4(p)-4.6(n)1.4(o)-4.6(tics to b)-4.6(e)5.1( pr)]TJ 15.2695 0 TD -.0002 Tc .0017 Tw [(escri)8.2(b)-3.2(ed would e)6.5(x)-3.2(agge)6.5(rate the haza)6.5(rd )]TJ -29.7964 -1.1497 TD -.0014 Tc .0029 Tw [(ratio)-4.4(s. )6( By in)-4.4(creasin)-4.4(g th)-4.4(e )6(risk )6(th)-4.4(at )]TJ 13.6946 0 TD .0016 Tc -.0001 Tw [(co)4.6(nve)8.3(rsel)4(y)10.6( a com)13(o)-1.4(r)5.3(b)-1.4(i)4(d)-1.4(i)4(t)4(y)4.6( cause)8.3(d )6(by)4.6( a )6(hy)4.6(pn)4.6(ot)4(i)4(c)2.3( m)13(i)4(ght)4( b)4.6(e)2.3( o)4.6(v)-1.4(e)8.3(r)17.2(-c)8.3(ont)10(rol)4(l)10(ed, )6(we )]TJ -13.6946 -1.1497 TD -.0007 Tc .0022 Tw [(accepted the )6(possibility that a)6(d)]TJ 12.3054 0 TD .0001 Tc .0014 Tw [(justm)11.5(e).8(nt for c)6.8(o)-2.9(m)11.5(o)-2.9(rbidities arising )6(during )]TJ 16.6647 0 TD .0002 Tc [(t)8.6(h)3.2(e pe)6.9(riods )6(of observation )6(woul)8.6(d c)6.9(r)-2.1(eate a )]TJ -28.9701 -1.1437 TD .0015 Tc 0 Tw [(bi)3.9(as )6(un)4.5(dere)8.2(st)3.9(i)3.9(m)6.9(at)3.9(i)3.9(ng t)3.9(h)-1.5(e t)3.9(r)5.2(ue)8.2( haza)8.2(rd)4.5( ra)]TJ 15.497 0 TD -.0018 Tc .0033 Tw [(tio)-4.8(s. )6(So)-4.8(m)9.6(e)-1.1(wh)-4.8(at to)-4.8( )6(ou)-4.8(r surprise, th)-4.8(e con)-4.8(s)-1.9(erv)-4.8(a)-1.1(tiv)-4.8(e )6(stratified)-4.8( an)-4.8(alyses u)-4.8(s)4.1(u)-4.8(a)-1.1(lly )]TJ -15.497 -1.1497 TD -.0013 Tc .0028 Tw [(p)-4.3(r)2.4(od)-4.3(u)-4.3(c)-.6(ed)-4.3( )6(HR as h)-4.3(i)7.1(g)-4.3(h)1.7( as C)7(o)-4.3(x )6(m)10.1(o)-4.3(d)-4.3(e)-.6(ls e)-6.6(m)10.1(p)-4.3(l)1.1(o)-4.3(y)1.7(in)-4.3(g)-4.3( )6(on)-4.3(ly un)-4.3(stratified)-4.3( co)-4.3(m)10.1(o)-4.3(rb)-4.3(id)-4.3(ities ascertained)-4.3( )6(p)-4.3(r)-3.6(i)7.1(o)-4.3(r t)7.1(o)-4.3( the )6(p)-4.3(e)-.6(ri)7.1(o)-4.3(d)-4.3(s)4.6( of )]TJ T* -.0017 Tc .0032 Tw [(o)-4.7(b)-4.7(s)4.2(erv)-4.7(a)-1(tio)-4.7(n as )6(co)-4.7(v)-4.7(a)5(riates. )6( )18(These altern)-4.7(ativ)-4.7(e )6(Co)-4.7(x m)9.7(o)-4.7(d)-4.7(e)-1(ls wh)-4.7(ich)-4.7( )6(d)-4.7(i).7(d or )6(d)-4.7(i).7(d )6(n)-4.7(o)-4.7(t).7( con)-4.7(t).7(ro)-4.7(l fo)-4.7(r )6(co)-4.7(m)9.7(o)-4.7(rb)-4.7(id)-4.7(ities first )]TJ 0 -1.1437 TD -.0003 Tc .0018 Tw [(diagnosed in t)8.1(h)2.7(e pe)6.4(riod )6(of )6(obs)5.6(e).4(rvation alm)11.1(o)-3.3(st always)]TJ 21.2575 0 TD 0 Tc -.0045 Tw [( )-6(yielded hazard ratios with )]TJ 10.8383 0 TD .0006 Tc .0009 Tw [(ove)7.3(rlappi)9(ng 95%)7.3( Confi)9(d)3.6(ence )]TJ -32.0958 -1.1497 TD -.0017 Tc .0032 Tw [(In)-4.7(terv)-4.7(als. 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)6(212,292 pat)8.4(i)2.4(ents who recei)8.4(ve)]TJ 15.6347 0 TD -.0008 Tc .0023 Tw [(d no )6(hypnotic. )18(Thus, t)7.6(h)-3.8(e )6(pri)-4.4(m)10.6(ary care )]TJ -30.8264 -1.1437 TD -.0005 Tc -.004 Tw [(population consisted )-6(of 224,757 )-6(patients)5.4(,)]TJ 16.4132 0 TD .0006 Tc -.0051 Tw [( of whom)12( )-6(5.5% ha)7.3(d receive)7.3(d )-6(a hy)9.6(pnotic)]TJ 15.9042 0 TD .0001 Tc .0014 Tw [( presc)6.8(r)-2.2(iption. )6( )18(T)72(w)3.7(o c)6.8(o)3.1(ntrol )6(nonuse)6.8(rs )]TJ -32.3174 -1.1497 TD .0012 Tc .0003 Tw [(fo)4.2(r eac)7.9(h )6(user)4.9( w)4.8(e)1.9(re sel)3.6(ect)3.6(ed)4.2( w)4.8(h)-1.8(en)4.2( p)4.2(o)-1.8(ssi)9.6(bl)3.6(e;)3.6( m)6.6(a)1.9(t)3.6(c)1.9(hed by)4.2( )6(ge)7.9(nde)7.9(r)40.8(,)-.3( a)7.9(g)-1.8(e )6(wi)3.6(t)3.6(h)-1.8(i)9.6(n)-1.8( )6(5 y)4.2(ears)7.1(,)-.3( )6(begi)9.6(nni)9.6(ng)4.2( o)4.2(f)-1.1( )6(o)4.2(b)-1.8(ser)4.9(v)-1.8(at)3.6(i)3.6(o)-1.8(n)4.2(,)-.3( a)7.9(n)-1.8(d)4.2( )]TJ T* .0016 Tc -.0001 Tw [(whet)10(her)5.3( t)4(h)-1.4(e )6(pa)8.3(t)4(i)4(e)2.3(nt)4( had)4.6( e)8.3(v)-1.4(er )6(s)7.5(m)13(oked. C)9.9(o)4.6(nt)4(r)5.3(o)-1.4(l)4(s)1.5( )6(had)4.6( n)4.6(o)-1.4(t)4( )6(had)4.6( a p)4.6(r)-.7(esc)8.3(r)-.7(i)4(p)-1.4(t)4(i)4(o)4.6(n )6(fo)4.6(r a)8.3(n)-1.4(y)4.6( hy)10.6(pn)4.6(ot)10(i)4(c)2.3( reco)4.6(rde)8.3(d)-1.4( )6(d)4.6(u)-1.4(r)5.3(i)4(ng t)10(h)-1.4(e )]TJ ET 280.26 594.24 12.78 .48004 re f BT 10.02 0 0 10.02 72 584.34 Tm .0017 Tc -.0002 Tw [(i)4.1(n)-1.3(t)4.1(e)2.4(rval)4.1( )6(fr)5.4(om)13.1( Janua)8.4(ry)4.7( )6(1, )6(2)4.7(0)-1.3(0)4.7(2)4.7( t)4.1(o)-1.3( Se)8.4(pt)4.1(em)13.1(ber )6(31)4.7(, )6(20)4.7(0)4.7(6)-1.3(. )6( Dat)4.1(a)8.4( f)5.4(o)-1.3(r a)8.4(n)4.7(ony)4.7(m)13.1(i)4.1(zed )6(users)7.6( a)8.4(n)-1.3(d)4.7( n)4.7(o)4.7(nus)7.6(ers i)10.1(n)-1.3(cl)4.1(u)4.7(d)-1.3(e)8.4(d)-1.3( )6(di)4.1(sg)4.7(ui)4.1(sed)4.7( )]TJ T* .0015 Tc 0 Tw [(age )6(whe)8.2(n)-1.5( e)8.2(n)-1.5(t)3.9(e)2.2(r)5.2(i)3.9(ng a)8.2( pe)8.2(ri)3.9(o)4.5(d)-1.5( )6(of)5.2( )6(obs)7.4(er)5.2(vat)3.9(i)3.9(o)-1.5(n)4.5( \()5.2(d)4.5(efi)3.9(n)-1.5(e)8.2(d)-1.5( )6(bel)3.9(o)4.5(w\),)6( )6(di)3.9(sg)4.5(ui)3.9(sed)4.5( dat)3.9(e)2.2( )6(of)5.2( deat)9.9(h i)3.9(f)-.8( )6(dec)8.2(eased,)6( ge)8.2(n)4.5(d)-1.5(er)41.1(, )6(et)3.9(hni)3.9(ci)3.9(t)3.9(y)70.4(, )]TJ 0 -1.1437 TD .0011 Tc .0004 Tw [(and)4.1( u)4.1(s)1(ual)3.5(l)3.5(y)4.1( i)3.5(n)-1.9(c)7.8(l)3.5(ude)7.8(d sm)12.5(oki)3.5(n)4.1(g)4.1( st)3.5(at)3.5(us, al)3.5(c)7.8(o)-1.9(h)4.1(o)-1.9(l)9.5( st)3.5(at)3.5(us, m)12.5(a)1.8(ri)3.5(t)3.5(a)1.8(l)3.5( st)3.5(at)3.5(us, )6(hei)3.5(g)4.1(ht)3.5( a)7.8(n)-1.9(d)4.1( wei)9.5(ght)3.5(,)5.6( rec)7.8(o)-1.9(r)4.8(d)-1.9(s )6(of)4.8( sel)3.5(ect)3.5(ed )6(of)22.7(fi)3.5(ce )]TJ 0 -1.1497 TD .0013 Tc .0002 Tw [(di)3.7(ag)4.3(no)4.3(ses, ca)8(n)4.3(cer )6(di)3.7(ag)4.3(nose)8(s)1.2( )6(on)4.3( m)12.7(e)2(di)3.7(cal)3.7( pro)4.3(b)-1.7(l)3.7(e)2(m)12.7( li)3.7(st)3.7(s, can)4.3(cer re)8(gi)3.7(st)3.7(ry)4.3( )6(dat)9.7(a)2( \()5(w)-1.1(he)8(n a)8(v)-1.7(ai)3.7(l)3.7(a)2(bl)3.7(e\),)5.8( an)4.3(d al)3.7(l)3.7( )6(pr)5(escri)3.7(p)-1.7(t)3.7(i)3.7(o)4.3(ns )6(fo)4.3(r )]TJ T* .0001 Tw [(hy)4.4(p)4.4(not)3.8(i)3.8(c)2.1( m)12.8(e)2.1(di)3.8(cat)3.8(i)3.8(ons )6(reco)4.4(r)5.1(d)-1.6(e)8.1(d)-1.6( el)3.8(ect)3.8(r)5.1(oni)3.8(cal)3.8(l)3.8(y)4.4( fr)5.1(om)12.8( 199)4.4(6)4.4(-)-.9(2)4.4(0)-1.6(0)4.4(7)-1.6(,)5.9( i)3.8(n)-1.6(cl)3.8(u)4.4(d)-1.6(i)3.8(n)4.4(g )6(exact)3.8( d)4.4(r)5.1(ug)4.4( an)4.4(d )6(dos)7.3(age)8.1( i)3.8(d)-1.6(e)8.1(n)-1.6(t)3.8(i)3.8(f)-.9(i)3.8(cat)3.8(i)3.8(on, )]TJ 0 -1.1437 TD -.0011 Tc -.0034 Tw [(n)-4.1(u)-4.1(m)10.3(b)-4.1(e)-.4(rs of d)-4.1(o)1.9(ses )-6(prescrib)-4.1(ed)-4.1(, n)-4.1(u)-4.1(m)10.3(b)-4.1(e)-.4(rs of )-6(refills, )-6(an)-4.1(d )-6(so)-4.1(m)10.3(e)-.4( )]TJ 23.5329 0 TD -.0016 Tc .0031 Tw [(in)-4.6(fo)-4.6(rm)9.8(atio)-4.6(n)-4.6( co)-4.6(ncern)-4.6(i)6.8(n)-4.6(g)1.4( ind)-4.6(i).8(catio)-4.6(n)-4.6(s)4.3( of )6(p)-4.6(r)-3.9(escri)6.8(p)-4.6(tio)-4.6(ns. )6( )6( )]TJ -23.5329 -1.1497 TD 0 Tc 0 Tw ( )Tj T* -.0017 Tc .0032 Tw [( )-3341.3(Th)-4.7(ere were a small n)-4.7(u)-4.7(m)9.7(b)-4.7(e)-1(r of in)-4.7(itially-ex)-4.7(t).7(racted)-4.7( us)]TJ 24.0719 0 TD -.0021 Tc .0036 Tw [(ers who h)-5.1(a)4.6(d)-5.1( )6(b)-5.1(een selected)-5.1( b)-5.1(ecau)-5.1(s)-2.2(e of )6(a m)9.3(e)-1.4(d)-5.1(i).3(catio)-5.1(n)-5.1( )]TJ -24.0719 -1.1437 TD .0016 Tc -.0001 Tw [(or)5.3(der)5.3( w)5.2(h)-1.4(i)4(c)2.3(h)4.6()7.6(whe)8.3(n)-1.4( )6(d)4.6(o)-1.4(sa)8.3(ge )6(d)4.6(i)4(rect)4(i)4(ons a)8.3(n)4.6(d i)10(ndi)4(cat)4(i)4(o)4.6(ns )6(wer)5.3(e)2.3( re)8.3(vi)4(ewe)8.3(d)-1.4()7.6(w)5.2(as n)4.6(o)-1.4(t)4( c)8.3(onsi)10(d)-1.4(er)5.3(ed a t)10(r)-.7(ue)8.3( hy)10.6(pn)4.6(ot)4(i)4(c)2.3( )]TJ 0 -1.1497 TD [(presc)8.3(r)-.7(i)4(p)-1.4(t)4(i)4(o)4.6(n )6(\(e.)6.1(g)-1.4(.,)6.1( p)4.6(h)-1.4(e)8.3(n)-1.4(o)4.6(b)-1.4(a)8.3(r)-.7(bi)4(t)10(a)2.3(l)4( )18(TID)5.2( f)5.3(o)-1.4(r)5.3( epi)4(l)10(epsy)4.6( )6(or i)10(n)-1.4(t)4(r)-.7(a)8.3(v)-1.4(e)8.3(n)-1.4(o)4.6(u)-1.4(s m)13(i)4(dazol)4(a)8.3(m)13( for ane)8.3(s)1.5(t)4(h)-1.4(esi)10(a)2.3(\) )6(or )6(w)5.2(hos)7.5(e )6(hy)4.6(pn)4.6(ot)4(i)4(c)2.3( )]TJ T* .0014 Tc .0001 Tw [(presc)8.1(r)-.9(i)3.8(p)-1.6(t)3.8(i)3.8(o)4.4(ns )6(d)4.4(i)3.8(d n)4.4(o)-1.6(t)3.8( )6(occu)4.4(r )6(d)4.4(u)4.4(r)-.9(i)3.8(n)4.4(g t)3.8(h)-1.6(e)8.1( pe)8.1(ri)3.8(o)4.4(d)-1.6( )6(of)5.1( o)4.4(b)-1.6(se)8.1(rvat)3.8(i)3.8(o)4.4(n.)5.9( )18(T)7.5(h)-1.6(ese )6(user)5.1(s )6(were)8.1( t)3.8(h)-1.6(e)8.1(n)-1.6( e)8.1(x)-1.6(cl)3.8(ude)8.1(d.)5.9( Li)9.8(kewi)3.8(s)7.3(e)2.1(, 1)4.4(3)4.4(1)-1.6( )]TJ 0 -1.1437 TD .0017 Tc -.0002 Tw [(pat)4.1(i)4.1(e)2.4(nt)4.1(s i)4.1(n)-1.3(t)4.1(e)8.4(nd)4.7(ed as)7.6( co)4.7(nt)4.1(r)5.4(o)-1.3(l)4.1( n)4.7(o)-1.3(n)4.7(u)-1.3(se)8.4(rs )6(were)8.4( f)5.4(o)-1.3(u)4.7(n)4.7(d)-1.3( t)4.1(o)4.7( ha)8.4(ve )6(h)4.7(y)4.7(p)-1.3(n)4.7(o)-1.3(t)4.1(i)4.1(c)2.4( m)13.1(e)2.4(di)4.1(cat)4.1(i)4.1(on )6(or)5.4(der)5.4(s)1.6( )6(bef)5.4(o)-1.3(re)8.4( t)4.1(h)-1.3(e )6(peri)10.1(od)4.7( )6(of)5.4( )]TJ 0 -1.1497 TD .0012 Tc .0003 Tw [(obs)7.1(er)4.9(vat)3.6(i)3.6(o)-1.8(n)4.2(,)-.3( a)7.9(n)4.2(d t)3.6(h)-1.8(e)7.9(s)1.1(e c)7.9(ont)3.6(r)4.9(o)-1.8(l)9.6(s)1.1( we)7.9(re e)7.9(x)-1.8(cl)3.6(u)4.2(d)-1.8(e)7.9(d)-1.8(. )6( Fi)3.6(nal)3.6(l)3.6(y)70.1(, )6(we )6(were)7.9( co)4.2(ncer)4.9(ne)7.9(d t)3.6(h)-1.8(at)3.6( t)9.6(h)-1.8(e )6(rat)3.6(e)1.9( )6(of)4.9( cance)7.9(r )6(di)3.6(ag)4.2(nos)7.1(es )6(was )]TJ T* -.0026 Tc -.0019 Tw [(h)-5.6(i)-.2(gh)-5.6(er )-6(in)-5.6( u)-5.6(s)-2.7(er)-4.9(s th)-5.6(an)-5.6( no)-5.6(nu)-5.6(ser)-4.9(s)-2.7( b)-5.6(e)-1.9(fo)-5.6(r)-4.9(e)4.1( )]TJ 14.6946 0 TD .0017 Tc -.0002 Tw [(t)4.1(h)-1.3(e c)8.4(o)-1.3(m)13.1(m)7.1(encem)13.1(e)2.4(nt)4.1( of)5.4( )6(t)4.1(h)-1.3(e pe)8.4(ri)4.1(o)4.7(d)-1.3(s )6(o)4.7(f)-.6( )6(obs)]TJ 16.2335 0 TD -.0018 Tc .0033 Tw [(erv)-4.8(a)-1.1(tio)-4.8(n. )6(Sin)-4.8(ce it is po)-4.8(ssi)6.6(b)-4.8(l).6(e th)-4.8(at a )]TJ -30.9281 -1.1437 TD .0013 Tc .0002 Tw [(cancer)5( di)3.7(a)8(g)-1.7(n)4.3(o)-1.7(s)7.2(i)3.7(s wo)4.3(ul)9.7(d ca)8(use )6(anxi)3.7(et)3.7(y)4.3( an)4.3(d i)9.7(n)-1.7(s)7.2(o)-1.7(m)12.7(n)-1.7(i)3.7(a)2( l)3.7(eadi)3.7(n)-1.7(g)4.3( )6(t)3.7(o)-1.7( hy)10.3(pn)4.3(ot)3.7(i)3.7(c)2( p)4.3(r)-1(e)8(s)1.2(cri)3.7(p)-1.7(t)3.7(i)3.7(o)4.3(n, i)9.7(n)-1.7( )6(w)4.9(h)-1.7(i)3.7(c)2(h ca)8(se t)3.7(h)-1.7(e)8( c)8(a)2(ncer)5( w)4.9(o)4.3(ul)3.7(d )]TJ 0 -1.1497 TD .0002 Tc .0013 Tw [(be ca)6.9(using t)8.6(h)-2.8(e )6(hypnotic c)6.9(o)-2.8(nsum)11.6(ption )6(rathe)6.9(r)-2.1( t)8.6(h)-2.8(an the c)6.9(o)3.2(nve)6.9(rs)]TJ 24.2216 0 TD -.0006 Tc .0021 Tw [(e, we e)6.1(x)-3.6(clude)6.1(d)-3.6( all users)5.3( an)]TJ 10.6946 0 TD 0 Tc -.0045 Tw [(d nonusers)5.9( )-6(that received any )]TJ -34.9162 -1.1497 TD .001 Tc .0005 Tw [(di)3.4(ag)4(no)4(si)3.4(s o)4(f)-1.3( ca)7.7(ncer)4.7( \()4.7(o)-2(t)3.4(h)-2(e)7.7(r)-1.3( t)3.4(h)-2(a)7.7(n)-2( )6(no)4(nm)12.4(el)]TJ 15.5449 0 TD .0001 Tc .0014 Tw [(anoma ski)8.5(n)-2.9( ca)6.8(ncer\) recorde)6.8(d)-2.9( )6(before)6.8( the )]TJ 16.024 0 TD .0019 Tc -.0004 Tw 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-1.1497 TD -.0002 Tc .0017 Tw [(Lack et al., )6(2006)]TJ 6.48 0 0 6.48 139.02 519.84 Tm 0 Tc 0 Tw (19)Tj 10.02 0 0 10.02 145.5 515.34 Tm .0024 Tc -.0069 Tw [( )-14443.1(2,)6.9(08)5.4(7)5.4( )-2161.7(13)5.4( )-6(y)5.4(r)6.1( )-4724.6(1.)6.9(12)5.4( )-832.3(P=0.)6.9(0)5.4(0)-.6(1)5.4( )]TJ -7.3353 -1.1497 TD -.0006 Tc .0021 Tw (Mallon et al., 2002)Tj 6.48 0 0 6.48 147.9 508.32 Tm 0 Tc 0 Tw (20)Tj 10.02 0 0 10.02 154.38 503.82 Tm -.0026 Tc .0041 Tw [( )6( )-13550.9(1)-5.6(,)1.9(8)-5.6(70 )-2155.7(1)-5.6(2).4( yr )-2694.6(6)-5.6(.)1.9(4)-5.6( & 3.8 )-826.3(P<0)-5.6(.)1.9(05 )]TJ -8.2216 -1.1437 TD -.0006 Tc .0021 Tw (Mallon et al., 2009)Tj 6.48 0 0 6.48 147.9 496.86 Tm 0 Tc 0 Tw (21)Tj 10.02 0 0 10.02 154.38 492.36 Tm -.0025 Tc -.002 Tw [( )-13556.9(3)-5.5(,)2(5)-5.5(23 )-2161.7(2)-5.5(0).5( )-6(yr )-4227.6(3)-5.5(.)2(2)-5.5(85 )-832.3(P<0)-5.5(.)2(00)-5.5(1 )]TJ -8.2216 -1.1497 TD .0016 Tc -.0001 Tw [(M)4.5(e)2.3(rl)4(o et)4( al)4(.,)6.1( )6(19)4.6(96)]TJ 6.48 0 0 6.48 143.46 485.34 Tm 0 Tc 0 Tw (22)Tj 10.02 0 0 10.02 149.94 480.84 Tm -.0027 Tc -.0018 Tw [( )-14748.5(4)-5.7(98 )-2155.7(1)-5.7(0).3( )-6(yr)-5( )-5227.6(1)-5.7(.)1.8(0 )-832.3(N)-5.1(S)2.6( )]TJ -7.7784 -1.1497 TD -.0017 Tc .0032 Tw [(Ph)-4.7(illip)-4.7(s & Man)-4.7(n)-4.7(i)6.7(n)-4.7(o)1.3(, )6(2)-4.7(005)]TJ 6.48 0 0 6.48 176.52 473.82 Tm 0 Tc 0 Tw (23)Tj 10.02 0 0 10.02 183 469.32 Tm -.0028 Tc -.0017 Tw [( )-10203.6(1)-5.8(3).2(,563 )-1910.2(6)-5.8(.)1.7(3)-5.8( )-6(yr )-5227.6(1)-5.8(.)1.7(4 )-832.3(N)-5.2(S)2.5( )]TJ -11.0778 -1.1437 TD -.0014 Tc .0029 Tw [(Ro)-4.4(d et al., )6(20)-4.4(10)]TJ 6.48 0 0 6.48 135.66 462.36 Tm 0 Tc 0 Tw (24)Tj 10.02 0 0 10.02 142.14 457.86 Tm -.0025 Tc .004 Tw [( )-14521(1)-5.5(6).5(,989 )-2155.7(1)-5.5(9).5( yr )-2395.2( 1)-5.5(.)2(07)-5.5(-1)-5.5(.30 )-826.3(P<0)-5.5(.)2(05)-5.5( & NS )]TJ -7 -1.1497 TD -.0026 Tc [(Ru)-5.6(m)8.8(b)-5.6(le & Mor)13(g)-5.6(an)-5.6(, 199)-5.6(2)]TJ 6.48 0 0 6.48 172.98 450.84 Tm 0 Tc 0 Tw (25)Tj 10.02 0 0 10.02 179.46 446.34 Tm -.0024 Tc .0039 Tw [( )6( )-11796.4(5)-5.4(77 )-2652.7(5)-5.4( yr )-2640.7(1)-5.4(.)2.1(1)-5.4(9).6(-1)-5.4(.2)-5.4(4 )-826.3(P=.027)-5.4( to 0.275 )]TJ -10.7246 -1.1497 TD -.0003 Tc .0018 Tw [(Sundquist, et a)6.4(l)2.1(.,1996)]TJ 6.48 0 0 6.48 159 439.32 Tm 0 Tc 0 Tw (26)Tj 10.02 0 0 10.02 165.48 434.82 Tm .0019 Tc -.0064 Tw [( )-11760.5(uncl)4.3(e)2.6(a)8.6(r)5.6( )-2155.7(10)4.9( )-6(y)4.9(r)-.4( )-4754.5(N/)4.3(A)5.5( )-832.3(P<0.)6.4(0)4.9(0)-1.1(1)4.9( )]TJ -9.3293 -1.1437 TD -.0019 Tc .0034 Tw [(Tho)-4.9(r)1.8(o)-4.9(goo)-4.9(d et al., 199)-4.9(2)]TJ 6.48 0 0 6.48 163.44 427.86 Tm 0 Tc 0 Tw (27)Tj 10.02 0 0 10.02 169.92 423.36 Tm -.0028 Tc -.0017 Tw [( )-12790.4(1)36.1(1)-5.8(2 )-2658.7(3)-5.8( )-6(yr )-3149.7(3)-5.8(.)1.7(7)-5.8(-).9(12)-5.8(.0 )-832.3(P<<0)-5.8(.05 )]TJ -9.7725 -1.1497 TD -.0004 Tc .0019 Tw [(W)33.3(i)8(nkelm)11(ayer et al, 2007)]TJ 6.48 0 0 6.48 170.52 416.34 Tm 0 Tc 0 Tw (28)Tj 10.02 0 0 10.02 177 411.84 Tm .0026 Tc -.0071 Tw [( )-11299.4(3,)7.1(63)5.6(0)5.6( )-1826.4(2-)6.3(4 )-6(y)5.6(r)6.3( )-4724.6(1.)7.1(15)5.6( )-832.3(P<0.)7.1(0)5.6(5)5.6( )]TJ -10.479 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1437 TD -.0018 Tc .0033 Tw [( )6( )59.9(As Sup)-4.8(p)-4.8(l).6(emen)-4.8(tary )18(T)70.1(a)-1.1(b)-4.8(l).6(e 1 )6(sh)-4.8(ows, th)-4.8(e great )-6(m)9.6(a)-1.1(j)-5.4(o)-4.8(rity)]TJ 22.1138 0 TD .0012 Tc .0003 Tw [( o)4.2(f)-1.1( )6(pre)7.9(v)-1.8(i)3.6(o)4.2(us )6(st)3.6(u)4.2(d)-1.8(i)3.6(e)1.9(s o)4.2(b)-1.8(ser)4.9(v)-1.8(e)7.9(d)-1.8( a)7.9( si)3.6(gni)9.6(fi)3.6(cant)3.6( ass)7.1(o)-1.8(c)7.9(i)3.6(at)3.6(i)3.6(on o)4.2(f)-1.1( )]TJ -22.1138 -1.1497 TD -.0001 Tc .0016 Tw [(sleeping )6(pill consum)11.3(ption wit)8.3(h)-3.1( m)11.3(o)-3.1(rtality)68.8(. )18(These st)8.3(udies)5.8( were)]TJ 24.503 0 TD [( )6(highly dive)6.6(rse in m)11.3(e).6(thodol)]TJ 10.9761 0 TD -.0005 Tc .002 Tw [(ogies, num)10.9(b)-3.5(ers of s)5.4(u)-3.5(bjects, )]TJ -35.479 -1.1497 TD -.0024 Tc .0039 Tw [(an)-5.4(d dur)-4.7(atio)-5.4(n of ob)-5.4(serv)-5.4(ation)-5.4(.)-3.9( )6( )24(Th)-5.4(e )6(r)-4.7(i)0(sk r)-4.7(a)-1.7(tio)-5.4(s )6(r)-4.7(e)-1.7(po)-5.4(r)-4.7(t)0(ed)-5.4( )6(w)-4.8(e)-1.7(r)-4.7(e)4.3( )6(v)-5.4(a)-1.7(r)-4.7(i)0(ab)-5.4(le, rang)-5.4(i)6(n)-5.4(g fr)-4.7(o)-5.4(m)9( 1)-5.4(.)2.1(0)-5.4( to )6(1)-5.4(2).6(.0, )6(b)-5.4(u)-5.4(t)0( i)6(n)-5.4( )6(o)-5.4(n)-5.4(l)6(y o)-5.4(n)-5.4(e)4.3( of)-4.7( )6(22)-5.4( )]TJ 0 -1.1437 TD -.0006 Tc .0021 Tw [(studies )6(did the )6(risk )6(ratio )6(fail to e)6.1(x)-3.6(ceed 1.0. )6(It seem)10.8(s )]TJ 21.006 0 TD -.0001 Tc .0016 Tw [(plausible that factors )6(produc)]TJ 11.3473 0 TD -.0005 Tc .002 Tw [(i)7.9(n)-3.5(g va)6.2(riability in risk ratios )]TJ -32.3533 -1.1497 TD .0014 Tc .0001 Tw [(i)3.8(n)-1.6(cl)3.8(ude)8.1(d )6(sam)12.8(p)-1.6(le age a)8.1(n)4.4(d )6(heal)3.8(t)3.8(h)-1.6( st)3.8(at)3.8(us)7.3(, t)3.8(h)-1.6(e)8.1( va)8.1(ri)3.8(o)4.4(u)-1.6(s )6(hy)4.4(p)4.4(not)3.8(i)3.8(c)2.1(s)7.3( use)8.1(d)-1.6( )6(by)4.4( t)3.8(h)-1.6(e)8.1( 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424.5 549.72 Tm 0 Tc 0 Tw (1)Tj 10.02 0 0 10.02 427.68 545.22 Tm -.0016 Tc -.0029 Tw [( )-6( )18(T)70.3(w)-4(elv)-4.6(e)-.9( b)-4.6(illio)-4.6(n)-4.6( d)-4.6(o)-4.6(s)4.3(es )]TJ -35.497 -1.1437 TD .0003 Tc .0012 Tw [(would be)7( s)6.2(u)-2.7(f)21.9(f)-2(icient to s)6.2(u)3.3(pply )6(53 de)7(fine)]TJ 15.6168 0 TD -.0003 Tc .0018 Tw [(d )6(daily dos)5.6(es )6(per year to each U.S. )6(adu)]TJ 15.5269 0 TD -.0008 Tc .0023 Tw [(lt, )6(or )6(nightly dos)5.1(es to approxim)10.6(a)-.1(tely )]TJ -31.1437 -1.1497 TD -.0019 Tc .0034 Tw [(1)-4.9(4)1.1(.5% )6(o)-4.9(f)-4.2( adu)-4.9(lts, bu)-4.9(t t)6.5(h)-4.9(e Ch)-4.9(ief of th)-4.9(e Psycho)-4.9(t)6.5(r)-4.2(op)-4.9(ics C)6.4(o)-4.9(n)-4.9(t)]TJ 22.5928 0 TD -.002 Tc .0035 Tw [(ro)-5(l )6(Sectio)-5(n)-5( )6(of th)-5(e In)-5(tern)-5(atio)-5(n)-5(a)-1.3(l )6(Narco)-5(tics C)6.3(o)-5(n)-5(t)6.4(rol Bo)-5(ard)-5( )]TJ -22.5928 -1.1497 TD -.0001 Tc .0016 Tw [(Secretariat a)6.6(d)-3.1(vised that t)8.3(h)-3.1(is es)5.8(tim)11.3(a)-5.4(ted re)6.6(qui)8.3(re)-5.4(m)11.3(e).6(nt is )]TJ 22.1976 0 TD .0001 Tc .0014 Tw [(likely to be)6.8( a )6(great )6(exagge)6.8(ra)]TJ 11.2814 0 TD -.0021 Tc .0036 Tw [(tio)-5.1(n \(p)-5.1(erson)-5.1(a)-1.4(l co)-5.1(mmu)-5.1(n)-5.1(i).3(cation)-5.1(\))1.6(, )]TJ -33.479 -1.1437 TD .0014 Tc .0001 Tw [(si)3.8(nce i)3.8(t)3.8( i)3.8(s)1.3( t)3.8(h)4.4(o)4.4(u)4.4(ght)3.8( t)9.8(o)-1.6( )6(be m)12.8(o)-1.6(re )6(t)3.8(h)-1.6(an )6(8 t)3.8(i)3.8(m)12.8(es t)3.8(h)-1.6(e 2)4.4(0)-1.6(0)4.4(8)-1.6( )6(U.)5.9(S. c)8.1(o)4.4(nsum)12.8(pt)3.8(i)3.8(o)-1.6(n)4.4(.)-.1( )6(In)4.4(deed)4.4(, )6(12)4.4(2,)5.9(5)4.4(4)-1.6(2)4.4(,)5.9(43)4.4(0 )6(g)4.4(r)-.9(am)12.8(s of z)8.1(o)-1.6(l)3.8(p)-1.6(i)3.8(d)-1.6(em)12.8( )]TJ 0 -1.1497 TD -.0019 Tc .0034 Tw [(wou)-4.9(l).5(d b)-4.9(e)4.8( m)9.5(o)-4.9(re th)-4.9(an 4 ti)-5.5(m)9.5(e)-1.2(s th)-4.9(e to)-4.9(tal )6(g)-4.9(l).5(ob)-4.9(al )6(man)-4.9(u)-4.9(f)-4.2(act)6.5(u)-4.9(r)-4.2(e of zo)-4.9(lp)-4.9(i)6.5(d)-4.9(em)9.5( fo)-4.9(r 20)-4.9(08)-4.9(. Prob)-4.9(ab)-4.9(ly)67(, actu)-4.9(a)-1.2(l 201)-4.9(0 U.S. zo)-4.9(lp)-4.9(id)-4.9(em)9.5( )]TJ T* .0018 Tc -.0003 Tw [(con)4.8(s)1.7(um)13.2(pt)4.2(i)4.2(on )6(w)5.4(a)2.5(s som)13.2(e)2.5(whe)8.5(r)-.5(e )6(bet)4.2(w)-.6(ee)8.5(n t)4.2(h)-1.2(e)8.5( 2)4.8(0)4.8(0)-1.2(6)4.8(-)5.5(20)4.8(0)4.8(8)-1.2( c)8.5(ons)7.7(u)4.8(m)13.2(pti)4.2(on a)8.5(n)-1.2(d)4.8( t)4.2(h)-1.2(e)8.5( 2)4.8(0)-1.2(1)4.8(0)-1.2( e)8.5(s)1.7(t)4.2(i)-1.8(m)13.2(a)2.5(t)4.2(e)-3.5(d )8.5(r)-.5(eq)4.8(ui)4.2(rem)13.2(e)2.5(nt)4.2(. )18(T)7.9(h)-1.2(e )]TJ 0 -1.1437 TD .0013 Tc .0002 Tw [(est)3.7(i)-2.3(m)12.7(a)2(t)3.7(e)2(d 20)4.3(1)40.2(1)4.3( re)8(qui)3.7(rem)12.7(e)2(nt)3.7( was )6(1)4.3(9)-1.7(,)5.8(5)-1.7(7)4.3(2)4.3(,)-.2(9)4.3(0)4.3(0)-1.7( )6(gram)12.7(s.)]TJ 6.48 0 0 6.48 287.1 469.26 Tm 0 Tc 0 Tw (2)Tj 10.02 0 0 10.02 290.34 464.76 Tm ( )Tj -21.7904 -1.1497 TD ( )Tj T* -.0004 Tc .0019 Tw [( )-3341.3(There)6.3( are)6.3( seve)6.3(ral reas)5.5(ons to s)5.5(u)-3.4(spect )]TJ 18.1677 0 TD -.0027 Tc .0042 Tw [(th)-5.7(at an)-5.7( )6(esti)-6.3(m)8.7(a)-2(te o)-5.7(f)-5( 3.06)-5.7(25)-5.7(% of)-5( )6(U)-5.1(.)-4.2(S.)]TJ 14.2755 0 TD -.002 Tc -.0025 Tw [( )-6(ad)-5(u)-5(lts u)-5(s)-2.1(ing)-5( h)-5(ypn)-5(o)-5(tics n)-5(i).4(gh)-5(tly )-6(is )]TJ -32.4431 -1.1437 TD .0001 Tc .0014 Tw [(likely to be)6.8( an )6(unde)6.8(restim)11.5(ate for )6(2010.)]TJ 6.48 0 0 6.48 226.68 434.76 Tm 0 Tc 0 Tw (2)Tj 10.02 0 0 10.02 229.92 430.26 Tm -.0015 Tc .003 Tw [( )6( )18(Th)-4.5(e In)-4.5(tern)-4.5(ation)-4.5(a)-.8(l )6(Narco)-4.5(tics Con)-4.5(t)6.9(ro)-4.5(l B)6.8(o)-4.5(ard)-4.5( esti)6.9(mate fo)-4.5(r )6(20)-4.5(07-2)-4.5(009)-4.5( )6(U.S. )]TJ -15.7605 -1.1497 TD -.0013 Tc .0028 Tw [(co)-4.3(nsu)-4.3(m)10.1(p)-4.3(tio)-4.3(n)-4.3( )6(was abou)-4.3(t 9)-4.3(%)5.4( h)-4.3(i)7.1(g)-4.3(h)-4.3(e)5.4(r t)7.1(h)-4.3(an th)-4.3(e esti)-4.9(m)10.1(a)-.6(te fo)-4.3(r th)-4.3(e )6(in)-4.3(terv)-4.3(al )6(1)-4.3( year )6(earlier)50.3(.)]TJ 6.48 0 0 6.48 399.72 423.24 Tm 0 Tc 0 Tw (2)Tj 10.02 0 0 10.02 402.96 418.74 Tm .0019 Tc -.0004 Tw [( C)10.2(o)-1.1(n)4.9(s)1.8(u)4.9(m)13.3(pti)4.3(on )6(has a)8.6(p)4.9(p)4.9(a)2.6(rent)4.3(l)4.3(y)4.9( )]TJ -33.0299 -1.1497 TD -.0003 Tc .0018 Tw [(increase)6.4(d)-3.3( si)8.1(nce)6.4( mid 2007, when lowe)]TJ 14.9641 0 TD 0 Tc .0015 Tw [(r)15.6(-)3.7(priced )6(gene)6.7(ric z)6.7(o)-3(lpi)8.4(d)-3(em)11.4( becam)11.4(e a)-5.3(v)]TJ 14.7784 0 TD .0001 Tc .0014 Tw [(ailable, acc)6.8(ording to ne)6.8(ws)6(pa)6.8(per )]TJ -29.7425 -1.1437 TD -.0009 Tc .0024 Tw [(summ)10.5(aries of )6(data collected )6(by IMS Health.)]TJ 6.48 0 0 6.48 248.34 400.26 Tm 0 Tc 0 Tw (3)Tj 10.02 0 0 10.02 251.58 395.76 Tm -.0018 Tc -.0027 Tw [( )47.9(Also)-4.8(, )-6(th)-4.8(e In)-4.8(t)6.6(e)-1.1(rn)-4.8(ation)-4.8(a)-1.1(l Narco)-4.8(tics )-6(Con)-4.8(t).6(ro)-4.8(l Bo)-4.8(ard)-4.8( d)-4.8(i).6(d)-4.8( no)-4.8(t )-6(in)-4.8(clud)-4.8(e )]TJ -17.9222 -1.1497 TD -.0005 Tc .002 Tw [(zaleplon or es)5.4(z)6.2(opiclone i)7.9(n)-3.5( its )6(estim)10.9(a).2(tes )]TJ 15.8443 0 TD .0018 Tc -.0003 Tw [(of hy)10.8(pn)4.8(ot)4.2(i)4.2(c)2.5( co)4.8(ns)7.7(um)7.2(pt)4.2(i)4.2(o)-1.2(n)4.8(.).3( )6(Fu)4.8(rt)4.2(her)47.4(,)6.3( t)4.2(h)-1.2(e )6(Int)4.2(e)2.5(r)5.5(n)-1.2(at)4.2(i)4.2(o)4.8(n)4.8(a)2.5(l)4.2( Narc)8.5(ot)4.2(i)4.2(c)2.5(s C)10.1(ont)10.2(rol)4.2( B)10.1(o)-1.2(ar)5.5(d )]TJ -15.8443 -1.1497 TD -.0016 Tc .0031 Tw [(d)-4.6(o)-4.6(e)5.1(s )6(n)-4.6(o)-4.6(t).8( i)6.8(n)-4.6(clude sed)-4.6(a)-.9(tiv)-4.6(e an)-4.6(ti)6.8(h)-4.6(i).8(stamin)-4.6(es su)-4.6(ch)-4.6( as d)-4.6(i)6.8(p)-4.6(h)-4.6(e)5.1(nh)-4.6(ydram)9.8(in)-4.6(e in)-4.6( its co)-4.6(m)9.8(p)-4.6(ilatio)-4.6(n)-4.6(s)-1.7(, tho)-4.6(ugh)-4.6( it is recog)-4.6(n)-4.6(i).8(zed)-4.6( th)-4.6(at)6.8( )]TJ 0 -1.1437 TD -.0017 Tc [(th)-4.7(ese )6(d)-4.7(r)2(u)-4.7(g)1.3(s con)-4.7(s)-1.8(titu)-4.7(te a su)-4.7(bstan)-4.7(tial p)-4.7(o)1.3(rtion)-4.7( )6(of th)]TJ 19.1018 0 TD -.0025 Tc .004 Tw [(e drug)-5.5(s prescrib)-5.5(ed)-5.5( )6(for )]TJ 8.976 0 TD -.0012 Tc .0027 Tw [(treat)-4.8(m)10.2(en)-4.2(t o)-4.2(f)-3.5( i)7.2(n)-4.2(so)-4.2(m)10.2(n)-4.2(ia.)]TJ 6.48 0 0 6.48 443.58 365.76 Tm 0 Tc 0 Tw (1)Tj 10.02 0 0 10.02 446.82 361.26 Tm -.0016 Tc .0031 Tw [( Sed)-4.6(a)-.9(tiv)-4.6(e )]TJ -37.4072 -1.1497 TD .0001 Tc .0014 Tw [(antidepressa)6.8(nts)6( suc)6.8(h)-2.9( as)6( traz)6.8(odone)6.8( or )6(doxe)6.8(pin are als)6(o)-2.9( c)6.8(o)]TJ 22.509 0 TD -.0022 Tc -.0023 Tw [(mmo)-5.2(n)-5.2(l).2(y u)-5.2(s)-2.3(ed)-5.2( )-6(as hyp)-5.2(no)-5.2(tics, b)-5.2(u)-5.2(t).2( )-6(t)6.2(h)-5.2(ese w)-4.6(e)-1.5(r)-4.5(e)4.5( )-6(no)-5.2(t )-6(i)6.2(n)-5.2(clud)-5.2(ed )]TJ -22.509 -1.1437 TD -.0014 Tc .0029 Tw [(eith)-4.4(er in th)-4.4(e )6(In)-4.4(tern)-4.4(ation)-4.4(a)-.7(l )6(Narco)-4.4(tics Con)-4.4(t)1(ro)]TJ 17.2156 0 TD -.0022 Tc .0037 Tw [(l )6(Bo)-5.2(ard)-5.2( st)6.2(u)-5.2(d)-5.2(y).8( )6(o)-5.2(r)1.5( in)-5.2( th)-5.2(e presen)-5.2(t )6(research)-5.2(. )]TJ -17.2156 -1.1497 TD 0 Tc 0 Tw ( )Tj 0 -1.1617 TD ( )Tj /TT12 1 Tf 3.5928 0 TD -.0008 Tc .0023 Tw [(Review )6(of epi)7.6(d)-1.5(emiologic s)5.1(t)-3.1(udies of hypnotics )]TJ /TT10 1 Tf -3.5928 -1.1317 TD 3.3428 Tc 0 Tw ( )Tj 0 -1.1497 TD -.0015 Tc .003 Tw [( )-3341.3(Prior to th)-4.5(is )6(rep)-4.5(o)1.5(rt, )6(24)-4.5( )6(p)-4.5(u)1.5(b)-4.5(lish)-4.5(e)-.8(d stud)-4.5(ies )6(h)-4.5(a)5.2(v)-4.5(e)-.8( ex)-4.5(am)9.9(in)-4.5(ed)-4.5( mo)-4.5(rtality related)-4.5( )6(to)-4.5( sleep)-4.5(i)6.9(n)-4.5(g p)-4.5(ill u)-4.5(s)-1.6(e, as sho)-4.5(w)2.1(n)-4.5( )6(in)-4.5( )]TJ T* .0016 Tc -.0181 Tw [(Su)4.6(ppl)4(em)13(ent)4(a)2.3(ry)4.6( T)73.5(a)2.3(bl)4(e )-12(1.)6.1( )]TJ 0 -1.1437 TD 0 Tc 0 Tw ( )Tj ET endstream endobj 209 0 obj <>/Font<>/ProcSet[/PDF/Text]>> endobj 207 0 obj <>/Font<>/ProcSet[/PDF/Text]>> endobj 216 0 obj <> endobj 217 0 obj <> endobj 218 0 obj <> endobj 223 0 obj <> endobj 224 0 obj <>stream h{y`Ts=Ν}&lef2$aJ0,@ 4l :H) ZR`Q\IqyQkŪնJH9g`{sy=9&V ̬SP8]Oĵcj-f `LrN|mIҕf4v+/㧮Gv}wTcvLh<V{Fuk.]8+:ٕ-:B߆彫ZV}< `>oqU6\ֹwa0/J?_bYP#8 Zj ͗n 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Give the rationale )Tj 11.475 0 TD .0002 Tc -.0012 Tw (for the choice of cases and )Tj -11.475 -1.15 TD .0006 Tc 0 Tw (controls)Tj /TT8 1 Tf 3.225 0 TD .0002 Tc -.0027 Tw (Cross sectional study)Tj /TT2 1 Tf 8.555 0 TD .0008 Tc -.0018 Tw [(?Give the elig)5.8(ibility)5.8( criteria, and)5.8( the )]TJ -11.78 -1.15 TD .0005 Tc [(sources and m)8.3(e)-.7(thods of s)-5.3(e)-.7(le)]TJ 11.225 0 TD -.0001 Tc -.0015 Tw (ction of participants )Tj -11.225 -1.575 TD 0 Tc 0 Tw (\()Tj /TT8 1 Tf .335 0 TD (b)Tj /TT2 1 Tf .5 0 TD .002 Tc (\) )Tj /TT8 1 Tf .585 0 TD .0001 Tc -.0001 Tw (Cohort study)Tj /TT2 1 Tf 5.19 0 TD .0005 Tc -.0013 Tw [(?)-5.7(F)1.7(or m)8.3(a)-.7(tched studies, give m)8.3(a)-.7(tching criteria and )]TJ -6.61 -1.15 TD .0004 Tc [(num)8.2(b).4(er of exposed and unexposed )]TJ 1 0 0 rg 14.38 0 TD .0006 Tc -.0006 Tw (Pages 6-7)Tj 0 g 3.92 0 TD 0 Tc 0 Tw ( )Tj /TT8 1 Tf .25 0 TD .0004 Tc (Case-control )Tj -18.55 -1.15 TD .0006 Tc (study)Tj /TT2 1 Tf 2.11 0 TD .0003 Tc -.0003 Tw [(?)-5.9(F)1.5(or m)8.1(a)-.9(tched studies, give m)8.1(a)-.9(tching criteria and the number )]TJ -2.11 -1.15 TD -.0015 Tw (of controls per case )Tj -12.115 -3.3 TD -.0005 Tc 6.2455 Tw (Variables 7 )Tj 12.115 1.725 TD .0001 Tc -.0001 Tw [(Clearly define all outcom)7.9(es, )]TJ 11.52 0 TD .0008 Tc -.0008 Tw (exposures, predic)Tj 7.005 0 TD .0002 Tc -.0002 Tw (tors, potential )Tj -18.525 -1.15 TD (confounders, and effect modifiers. )Tj 14 0 TD .0001 Tc -.0001 Tw (Give diagnostic)Tj 6.305 0 TD -.0001 Tc -.0024 Tw ( criteria, if )Tj -20.305 -1.15 TD .0011 Tc -.0011 Tw [(applic)4.9(able )]TJ 1 0 0 rg 4.61 0 TD .0004 Tc -.002 Tw (Covariate categories are in)Tj 0 g 10.69 0 TD 0 Tc 0 Tw ( )Tj 1 0 0 rg .25 0 TD .0003 Tc -.0003 Tw (Table 1, pages 22-23. )Tj -15.55 -1.15 TD -.0001 Tc .0001 Tw (Confounders are defined in Supplementary Table 2, page 37-38. )Tj 0 g 25.965 0 TD 0 Tc 0 Tw ( )Tj ET endstream endobj 248 0 obj <>/Font<>/ProcSet[/PDF/Text]>> endobj 244 0 obj [251 0 R] endobj 245 0 obj <>stream HWr+R"yA.R\rT"+waR#pDƃOw@ʥJy>}Յ?jsvO6ś?aEɐE}JA&U~y*|rƸ=93cOMyb2.֦ʍpȇ4{l2}_6p2ꎬaXdj 2ku֭u3/fq.peƭoxy"DC >\xdZg=%̘D3 x2]W P`cShjz.;Ve&7M̋TwS{سgM=)j 3 +cb&$m}| ~DzY~@4=?x+=_eK&@!i- !2C֙1;X+ ] ԻMЦO(f_vu.w[1v@'ں03?weGr<; H9]g( w* Q iNT=ŋ汌Ɣ^Y{q8T b#+ p>>T4!c=-@-x)/P23͝si:Õ!xo=슲IT(~fʋy4K nj},,QWK,U7Xd+ſtfv g S!:Tmd[1ݲA*Op|?[ZHAW߬P{66ii6YDSxo!TOjM zҺ麶NT71%7Eb^=r"YMo0`47d8'>y-+ApYx 5[D`X4I[/R"PQQ˞_HF0d +:}J9Xen,7e 2)Nt%Jqђ1ْ G,5Pf!O>;6xg`j&9Zs.KKޠf ^9X ~ S"͕MVTu ǫ.u}OXAuZ12$L>'lAbmCOPT&ӭJmsJ4?i3ky[Ͼ%P1 _t'e)obf&Rg(gLկ/7`Տ27'a*H:oԷͨ,Ue 9823Fk@+P3 =< ΅.w+, $|2(vE_ o.Tn>ǠˉaQJHm^Ʒ |΂}TtcCM  QqTdg*ZiWþ>$.8 TOB9;`ʌ <ީ4@~#E tB@j[MKh.اgoJ,Tk}~4pmԖNjN*qTW< $m= lhD=49g9"kрNЋ| (C57\F BKU{Mn Nײ*LJs}jbHhRZ?ķ,JO$[$Vg0AhrXf=1p=3<]IDL8~m%OuVqD~݉!e/BxI# A* KA#*=*|!Gn!G`3 %#5uJ1cUB y3`rc4ڧk[̹uhhے`$H 1q.QUX7l_C-H ϼczcrە wrl\'Kz*ZL-lGvNy"`( rN.)[.@.-x`V'SmC iNl8iߖMc_P{ե%D׷ Հ LE0Ql{6Q &rSMƱlA ʪ`Jb1̀r@׸D>g^N%dIX@c*ʗsnL `q0(+إL\a!36إʔ Uਢ:,lLһVERfpTRJזJgu :+;D w!'( IeuOmzu|4uרOٖ^ 1uMW%EہctZB@ImbCv!$'B2]>\ڇ$2/vs"ǩal<J&^Zi5 xmmf7lul?Qrc,F$VFI ?b^ G8.WX!cU+t;uFݟ'TUmm]Eo)%,dC9?Q 'ec:ϯMWBa"U^}pp{w JopդV endstream endobj 57 0 obj <> endobj 42 0 obj <> endobj 60 0 obj <> endobj 58 0 obj <> endobj 59 0 obj <> endobj 71 0 obj <> endobj 239 0 obj <> endobj 75 0 obj <> endobj 89 0 obj <>stream H4mHSq52O^SBJ MA e?XIcb,-SRCY40A ̬ ,Q)C%AF3+9bXO=*OkJ0/v] ]nm"wΨhP"&C0%l`L2JP8W=C?zYzɌj11#'D,ݑ`0}%en] lȇqq*ڦG:FB!N:Q pzgg ,MU£@-L@/Âi5vc[:K@);)?TaoX;cj/ X+z) endstream endobj 54 0 obj <> endobj 90 0 obj <>stream HTiTWu#PLPT@XE6D "(DEqe_5 H&N8( #D "* "ą^p0sy|{=T*fΛ3{U_ϰd*? k苂JAI'1)7J2Y&i*IHD{=IO/4\!͗VJ(t"t*uuG-ʦV./YFH3yBM^C"^Ѩo;"rDKx Ff6b=j;UIݠ>;rKT}*:`PIZ%Lu@yQxYTҁw?im$/F%غݙ3),l  3`4:qyB8;%ʓok$3ekꎬZ:ziWBm4tGiɍTEn8#V\Xs?c<?1D0N`}C^)4ǹ R{heRvuLb8`oQ}4Պ[2Vd8j8Nwc|XKJ<]H!{,`!&1ݶ IJǠE>(J,81hFCxā' 1L; M0"oWvɷ?Yua`~,nSL,_ ke߉$jP) %J/s0yKRcWO Ȣ6vsm}QOweXDy`4$, I HsHWb`4{{pՋOH\,+[y-Jw!(ɽ5貐XB(o ?.e=?Z<F*sqBSfW e\|AIפ-9ɢBֽUr~?sy} SX qǁ΀D1c~ D,BYC[qD;DMA|캰%K*s$ d٫#W Q& dCv0E`.ӊ@pC/hm⣜4~0mAM4Xd=u_R>V{]٠f+0~H%v 40yp=p#9՛s6+Y$77g۰/,9JQ9RVdU)7niboI6(Sjij%S~~O~j2UfNl gBHڀ llVEgEgV '3*JxlVCnaTTV0ZR`ma*8 IMpE5ZMIL`IDGh5k~*0 M6VQxEuaQ8)Q'p#JQ@x\ֈ7D)+\PDEP[X)#(-:qL:}3}wљn|'2UGS@GWph)!%DA!A< RN'oyGu[F,(eQ1n6 ^",*6+>c &W9,b ]k҈/1V6K257 7"c0bp=+m{P\5K˔WwvΗNz28?ʺKil,٠lvڜEm=_vh^wQXΖu%je'J~;27eOs (8;)J:fX$U#^' <6q_a0H ܬOBܡ%!i9?sou@<{-a;u[C $*cj/GVc=0Ssf_dUqi{VPr-M|Iۊ8]ק3iЛ2bpUN >I&l/+n=Vs`C`ytXqxg)m]O ^2k-lj_ ~HJ¤I&> endobj 96 0 obj <>stream Hj׮Zm9x^8~ww~WBK Ddqzyɹ b!6@ =?crGH1et;Ÿ ?&dDR o}D &\pL _ѵO:^:e˚x>L=cچ0m{8FZsbiIr)%G*}_t9t]K1T8e_ @/`"8b?K9pm! 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0000797024 00000 n trailer <]>> startxref 798825 %%EOF