! Miten!tauteja!tehdään?!

! Miten!tauteja!tehdään?!! Kari!Tikkinen!! HUS!Vatsakeskus/Urologia,!Helsingin!yliopiston!kansanterveys7eteen!osasto,!!Suomen!Akatemia!ja!CUE!Working!Group!! kari.7kkinen@gmail.com!!!!!!!!!!@karitikkinen! Suomen lääketieteen filosofian seura ry, Tieteiden talo, Helsinki, 7.4.2015

Sidonnaisuudet! Työnantajat!(palkallinen):! Helsingin!ja!Uudenmaan!sairaanhoitopiiri!(HUS)! Helsingin!yliopisto!/!Suomen!Akatemia!! Hoitosuositustyö!(palkaton!konsultoin7)!! uheenjohtaja:!euroopan!urologiyhdistyksen!(eau)! tromboosiprofylaksiahoitosuositusryhmä! Jäsen:!Euroopan!urologiyhdistyksen!(EAU)!miesten! virtsaamisoireiden!hoitosuositusryhmä! Jäsen:!Grading!of!Recommenda7ons!Assessment,! evelopment!and!evalua7on!(short!grae)!working!group!! Ei!kaupallisia!sidonnaisuuksia:!En!vastaanota!rahaa! lääketeollisuudelta!tai!laitevalmistajilta.!

Kysymyksiä!ja!agendaa! Mikä!on!normaalia!ja!mikä/mitä!on!sairaus?! Miten!ja!miksi!sairaus!luodaan?!! Tapaus!yliak7ivinen!virtsarakko!!

Ei!yhtä!oikeaa!kriteeriä!normaalille! ormaalijakauma!( Gaussin!käyrä )! 5%!epänormaaleja!joka!tes7llä! MiZaustaso,!johon!ei!liity!suurentunuZa!riskiä! Ylä!(tai!alapuolella)!miZaustasoa,!jolloin! hoidosta!on!enemmän!hyötyä!kuin!haizaa! Riippuu!hoidon!(arki)vaikuZavuudesta! Sosiaalises7,!polii\ses7!ja!kulZuurises7! hyväksyzävä! Sackett, Haynes RB, Guyatt GH, Tigwell. Clinical epidemiology: a basic science for clinical medicine. Boston: ittle, Brown: 1991:59.

Sairauden!käsite! Sairauden!käsite!on!vaikea!määritellä! Sairaudet,!taudit,!diagnoosit!ja!syndroomat! Yhä!useampia!7loja!määritellään!nykyisin!sairauksiksi 13! Riskitekijöiden!rajoja!alenneZu!!yhä!harvemmalla! normaalit! arvot! Uusia!oirepohjaisia!diagnooseja!kehiteZy!lisääntyväs7! Jonkin! 7lan!määriZelemisellä!sairaudeksi!voi!olla!sekä! posi7ivisia!ezä!nega7ivisia!vaikutuksia 24! 1. Kaplan & Ong. Annu Rev ublic Health 2007;28:321 2. Smith. BMJ 2002;324:883 3. Martin ym. BMJ 2014;349:g5432. 4. Temple ym. Science 2001;293:807

Terveyden!ja!sairauden!kirjo!?"?"?"?"?" Erittäin" sairaat" Täysin" terveet" Missä on sairauden raja?"

Terveyden!ja!sairauden!kirjo! Sairaat" Terveet" Erittäin" sairaat" Täysin" terveet" KAEA sairauden määritelmä" Edut: "Keskitytään sairaimpiin, jotka myös " " "todennäköisesti hyötyvät hoidosta eniten" " Haitat: Hukataan ihmisiä, jotka voisivat hyötyä"

Terveyden!ja!sairauden!kirjo! Sairaat" Terveet" Erittäin" sairaat" Täysin" terveet" EVEÄ sairauden määritelmä" Edut:"Tavoitetaan mahdollisimman moni, joka " "voisi hyötyä hoidosta" " Haitat: Terveiden ylidiagnosointi ja ylihoito"

Ideali<lanteessa!<eteellinen!näy=ö!määri=ää,!mu=a!yhä! useammin!muut!syyt!ja!perusteet!vaiku=avat!kriteereihin! $airaat! Terveet" Erittäin" sairaat" Täysin" terveet" EVEI sairauden määritelmä" ääketeollisuus, laitevalmistajat, lääkärit, tutkijat, " Woloshin ja Schwartz. os Med 2006;3:e170.

Alavirtsa<eoireiden!jao=elu!! Interna<onal!Con<nence!Society!(ICS)! Kerääntymisoireet (storage symptoms) Tihentynyt virtsaamisentarve (frequency) Virtsankarkailu (incontinence) Yövirtsaaminen (nocturia) Virtsaamispakko (urgency) Tyhjennysoireet (voiding symptoms) Virtsantulon viipyminen (hesitancy) Heikentynyt virtsasuihku (weak stream) onnistelun tarve virtsatessa (straining) Virtsauksen keskeytyminen Virtsaumpi (retention) Jälkioireet (post-micturition) Tiputtelu (post-micturition dribbling) Vajaan tyhjenemisen tunne Abrams ym. eururol Urodyn 2002;21:167-78.

Yliak<ivisen!(virtsa)rakon!määritelmä! International Continence Society n määritelmä suomennettuna: Yliaktiivisen rakon oireyhtymä on virtsaamispakko, johon voi liittyä virtsan pakkokarkailua, tihentynyttä virtsaamistarvetta ja yövirtsaamista. Määritelmän mukaan termiä voidaan käyttää, jos virtsatieinfektio tai muu ilmeinen syy on poissuljettu 1-3 1. Abrams ym. eururol Urodyn 2002:21:167 3. Tikkinen ym. uodecim 2007;123:2525 2. Abrams ym. eururol Urodyn 2006:25:293

Tieteellinen!terminologia!!vajavainen! spesifiteek/tarkkuus!! Overac7ve!bladder!syndrome!(OAB)!is! urgency,! with-or-without-urgency!incon7nence!usually-withincreased!day7me!frequency!and!nocturia.!! These!symptom!combina7ons!are!sugges7ve!of! urodynamically!demonstrable!detrusor!overac7vity,!butcan-be-due-to-other-forms!of!urethrovesical!dysfunc7on.! These!terms!can!be!used!if!there!is!no!proven!infec7on!or! other-obvious-pathology.! 2002!document!describes!also!as! urge!syndrome!or! urgencyfrequency!syndrome! Abrams et al. eurourol Urodyn 2002:21:167 Abrams et al. eurourol Urodyn 2006:25:293

Blaivas. BJU Int 2003:92:521 European Urology European Urology 47 (2005) 273 276 Editorial Overactive Bladder: A Clinical Entity or a Marketing Hype? Helmut Madersbacher euro-urology Unit, University Hospital, Medical University Innsbruck, Anichstrasse 23, A-6020 Innsbruck, Austria Accepted 20 October 2004 Available online 10 ovember 2004 Madersbacher. Eur Urol 2004:47:273

eurourology and Urodynamics OAB. Are We Barking Up the Wrong Tree? A esson From My og orman R. Zinner *, UCA Geffen School of Medicine, Western Clinical Research, Inc., os Angeles, California Zinner. eurourol Urodyn 2011:30:1410 I have never liked the term, OAB. At once, it says everything yet says nothing. It has been labeled many ways one of which is a syndrome. But what is it? It is urgency, with or without incontinence, usually with frequency and nocturia. So, if there is incontinence, frequency and nocturia it is not OAB. If it is urgency without frequency, nocturia or incontinence, it is OAB. So, while there are often associations, urgency alone is OAB. But what is urgency? It is a perception by an individual that cannot be quantitated by anyone but the individual. Since 2/3 of those with OAB do not have incontinence, how can one know he or she is about to lose urine when it has never happened? And, it is difficult to defer. ifficult is a very uncertain word. Things are somewhat difficult, very difficult, not so difficult. I think you get the point. However, it is more confusing than that. If you come home at night and have no desire to urinate and then, see the garage door go up as you press the opener button, you might have an overwhelming urge to urinate. Where did this come from? ot the bladder. The volume didn t change. When you hear someone urinating in your home or turn on the faucet, you might have a sudden urge to urinate. Where did this come from? ot the bladder. On the other hand, if you have a serious urge to urinate and the baby falls from the crib, or if you are in the operating room and need to void in the worst way and as you get set to ungown, the aorta cuts loose you forget all about that terrible urge and you are not incontinent. We in medicine find it hard to see something and not come up with an explanation whether based on evidence or personal or collected views. Some might call this expert opinion. But as scientists and those who apply our views to real patients, we have a responsibility to seek the evidence. Creating simplistic definitions and labels is not the way to go. It leads to no think. In so doing we make it easy to tell someone what they have. You have OAB. Aha, now I understand. What do we do? on t really know but let s try this or that. Wouldn t it be better to have the doctor in practice have to think about what he or she is facing rather than reaching into the cupboard, handing a pill, adding to expense, and walking into the next room? Some years ago I got into an argument with other well known urologists about instability and ultimately wrote something about it. The term was convenient as is OAB, but it implied that we knew something about the problem of urgency incontinence when we didn t. It stopped us from thinking. It also implied that there was something wrong with the bladder itself. Instability is a term with meaning. To be unstable suggests it vacillates, is not what it should be. But what if there was nothing wrong with the bladder and the brain is unstable. Would this be an unstable bladder or would it be an unstable brain? Sounds sort of silly either way. Richard Turner Warwick was an outstanding persona who did much for urology. Those of us who had the privilege of hearing him speak know he loved to quote from Humpty Tikkinen & Auvinen. Eur Urol 2012:61:746

Julkaisut!yliak<ivisesta!rakosta!(per!vuosi)! 800! 700! 600! 500! 400! 300! 200! 100! 0! 1998! 1999! 2000! 2001! 2002! 2003! 2004! 2005! 2006! 2007! 2008! 2009! 2010! Kaikki vuosina 1998-2010 yliaktiivista rakkoa käsittelevät artikkelit (Scopus) Tikkinen & Auvinen. Eur Urol 2012:61:746

Yliak<ivisen!rakon!markkinakehitys!USA:ssa! miljoonaa!dollaria!(us$)! 2500" 2000" 1500" 1000" 500" 0" 2007" 2008" 2009" 2010" 2011" IMS Health, verkossa osoitteessa http://www.imshealth.com/ims/global/content/corporate/ress%20room/ims%20in %20the%20ews/ocuments/Overactive_Bladder_Market1.pdf

ages 21 EURURO-4732; o. of ages 21 Miten!yliak<ivisen!rakon!lääkehoidot!tehoavat?!! Treatment, mg E U R O E A U R O O G Y X X X ( 2 0 1 2 ) X X X X X X Buser!ym.!Eur$Urol$2012;62:1040! ropiverine IR 45 4.27 (2.73 to 6.67); p < 0.001.5 1.7 ( 3.97 to 0.57); p = 0.142 de 40 1.36 ( 1.86 to 0.87); p < 0.001 521 1.36 ( 2.37 to 0.35); p = 0.009 1.30 ( 1.51 to 1.08); p < 0.001 EURURO-4732; Fesoterodine o. 8 of ages 3.4921 (2.42 to 5.03); p < 0.001 1.28 ( 1.49 to 1.07); p < 0.001 Trospium chloride 40 3.46 (2.21 to 5.40); p < 0.001 1.11 E U ( 1.41 R O E to A 0.81); U R O p O < G 0.001 Y X X X ( 2 0 1 2 ) X X X X X X E U R O E A U R O O G Y X X X ( 2 0 1 2 ) X X X X X X Oxybutynin IR 5 2.98 (0.93 to 9.52); p = 0.066 1.10 ( 2.55 to 0.34); p = 0.135 30 1.03 ( 1.67 to 0.39); VIRTSAAMISAKKOKERRAT p = 0.002 (/24h) Oxybutynin IR 10 2.44 (1.60 to 3.72); p < 0.001 VIRTSAAMISKERRAT (/24h) 3.9 1.02 ( 2.73 to 0.69); p = 0.241 Oxybutynin Treatment, IR 15mg 2.38 (0.98 to 5.81); p = 0.057 0 0.97 ( 1.76 to 0.19); p = 0.015 1.7 ( 3.97 to 0.57); p = 0.142 Fesoterodine 12 1.59 ( 3.15 to 0.03); p = 0.046 0 0.94 ( 1.34 to 0.54); p < 0.001 Tolterodine IR 4 2.36 (1.48 to 3.77); p < 0.001 1.36 ( 1.86 to 0.87); p < 0.001 Solifenacin 20 1.55 ( 3.24 to 0.13); p = 0.071 0.89 ( 1.28 to 0.50); p < 0.001 Oxybutynin IR 7.5 1.4 ( 4.06 to 1.26); p = 0.302 1.36 ( 2.37 to 0.35); p = 0.009 ropiverine IR 20 2.21 (1.18 to 4.14); p 0.013 5 0.8 ( 2.77 to 1.17); p = 0.425 Solifenacin 10 1.10 ( 1.32 to 0.87); p < 0.001 1.30 4 0.77 ( 1.51( 0.96 to 1.08); to 0.58); p < 0.001 p < 0.001 Fesoterodine Oxybutynin 4 IR 15 1.05 ( 1.78 to 0.31); p = 0.005 1.28 ( 1.49 to 1.07); p < 0.001 2.17 (1.53 to 3.07); p < 0.001 ropiverine IR 45 1.05 ( 1.82 to 0.28); p = 0.007 1.11 0.67 ( 1.41( 1.29 to 0.81); to 0.06); p < 0.001 p = 0.031 Oxybutynin Oxybutynin IR 9 IR 10 1.00 ( 1.60 to 0.40); p = 0.001 1.99 (1.36 to 2.91); p < 0.52 ( 0.96 to 0.07); p = 0.022 1.10 ( 2.55 to 0.34); p = 0.135 Trospium chloride 90 0.92 ( 1.78 to 0.05); p = 0.038 0 0.51 ( 1.10 to 0.07); p = 0.087 1.03 ( 1.67 to 0.39); p = 0.002 Tolterodine Fesoterodine ER 4 8 1.97 (1.62 0.91 ( 1.15 to 2.40); to 0.66); p < p < 0.001 15 0.50 ( 1.69 to 0.69); p = 0.410 Trospium chloride 40 0.86 ( 1.34 to 0.38); p < 0.001 1.02 ( 2.73 to 0.69); p = 0.241 Tolterodine IR 2 1.13 (0.65 to 1.98); p = 0.663 5 0.3 ( 1.51 to 0.91); p = 0.628 Solifenacin 5 0.85 ( 1.20 to 0.51); p < 0.001 0.97 0.07 ( 1.76 ( 1.29 to 0.19); to 1.42); p = p 0.015 = 0.923 ropiverine IR 20 0.83 ( 1.26 to 0.39); p < 0.001 0 2 4 6 8 10 0.94 ( 1.34 to 0.54); p < 0.001 Tolterodine IR 8 0.83 ( 2.83 to 1.17); p = 0.418 4 2 0 2 Tolterodine ER 4 0.76 ( 0.94 to 0.58); p < 0.001 erception of cure or improvement compared with placebo 0.89 ( 1.28 to 0.50); p < 0.001 Trospium chloride 60 0.76 ( 1.29 to 0.24); p = 0.004 0.8 ( 2.77 to 1.17); p = 0.425 (odds ratio 95% CI) Reduction in urgency episodes per 24 h compared with placebo Tolterodine IR 4 0.75 ( 1.05 to 0.46); p < 0.001 0.77 ( 0.96 to 0.58); p < 0.001 Oxybutynintopical gel 0.70 ( 1.33 to 0.07); p = 0.029 0.67 ( 1.29 to 0.06); p = 0.031 Mean. Tolterodine IR 95% 2 confidence 0.68 ( 1.45 interval. to 0.08); p = 0.081 5% confidence interval. Fesoterodine 4 0.64 ( 1.09 to 0.19); p = 0.005 0.52 ( 0.96 to 0.07); p = 0.022 ropiverine IR 30 0.57 ( 1.24 to 0.11); p = 0.100 0.51 ( 1.10 to 0.07); p = 0.087 Fig. 6 erception of cure or improvement compared with placebo (red line), assessed in 5245 patients. Results are shown as odds ratios and 95% Oxybutynin TS 3.9 0.56 ( 1.24 to 0.12); p = 0.106 ncy episodes per 24 h compared with placebo (red line), assessed in 19 479 patients. IR = immediate release; ER = confidence extended 0.50 ( 1.69 to 0.69); p = 0.410 intervals (CIs). ropiverine IR = immediate ER 30 release; 0.52 ER ( 1.27 = extended to 0.22); p = release. 0.167 system. 0.3 ( 1.51 to 0.91); p = 0.628 Imidafenacin 0.2 0.51 ( 1.22 to 0.20); p = 0.158 0.07 ( 1.29 to 1.42); p = 0.923 Oxybutynin ER 15 0.51 ( 1.71 to 0.69); p = 0.402 Solifenacin 2.5 0.25 ( 1.84 to 1.33); p = 0.753 procedure is described in Figure 1, and a study description is for reductions of urgency incontinence episodes (18 treatments), perception of cure or improvement (12 treatments), 4 2 0 2 Oxybutynin ER 5 0.23 ( 1.66 to 1.20); p = 0.751 0.16 ( 2.07 to 1.75); p = 0.871 provided in Table 1. Tolterodine The networks IR 1 are provided in the online Reduction in urgency episodes per 24 h compared with placebo Oxybutynin ER 10 0.15 ( 0.69 to 0.39); p = 0.582 appendix (Supplementary Fig. 1 6). Reductions of micturitions were assessed Oxybutynin for 31 different TS 2.6 0.08 ( 1.09 to 0.92); p = 0.873 and reductions of nocturia episodes (10 treatments) were utcomes. This efficacy parameter was Oxybutynin TS 1.3 0.08 ( 1.09 to 0.93); p = 0.874 3. Evidence synthesis onfidence drugs and formulations 17 251, 5245, and 13 247 patients, respectively. rse events interval. from the network metawas limited to treatments applied in 3.1. Efficacy outcomes Oxybutynin IR 2.5 1.8 ( 0.28 to 3.88); p = 0.090 in 32 020 patients. Reductions of leakage episodes were Figures 2 7 provide forest plots describing each treatment and dosage assessed against placebo for each outcome isodes per 24 h compared with placebo (red line), assessed in 19 479 patients. IR = immediate release; ER = extended assessed in 23 treatment modalities in 14 807 patients. tice. 4 2 0 2 4. Reductions of urgency episodes were assessed for 20 drugs assessed. rugs and dosages were rank ordered according to formed with Stata SE v.11.1. (Stataon, TX, USA). In total, 76 studies, including a total of 38 662 patients, were Reduction in micturition per 24 h compared with placebo and dosages in 19 479 patients. The corresponding numbers extent of efficacy. VIRTSA AKKOKARKAIUKERRAT (/24h) es. This efficacy parameter was 3. Evidence synthesis vents from the network metalimited to treatments applied in 2.25 ( 3.11 to 1.38); p < 0.001 0 2.20 ( 3.35 to 1.05); p < 0.001 3.1. Efficacy outcomes 0.86 ( 1.95 to 0.24); p = 0.124 ed with 0.78 Stata ( 1.01 SE to v.11.1. 0.56); p (Stata- < 0.001 In total, 76 studies, including a total of 38 662 patients, were X, USA). 0.76 ( 1.60 to 0.08); p = 0.075 available for analysis [21,22,25 96]. The study selection e 60 0.67 ( 1.01 to 0.33); p < 0.001 0.65 ( 0.96 to 0.34); p < 0.001 0.58 ( 0.76 to 0.41); p < 0.001 0 0.54 ( 0.89 to 0.19); p = 0.003 0 2.25 ( 3.11 0.53 ( 0.92 to 1.38); to 0.15); p < 0.001 p = 0.007 al 2.20 gel ( 3.35 0.50 ( 0.91 to 1.05); to 0.09); p < 0.001 p = 0.017 0.86 ( 1.95 0.49 ( 0.98 to 0.24); to p 0.01); = 0.124 p = 0.047 0.78 ( 1.01 0.42 ( 0.75 to 0.56); to 0.09); p < 0.001 p = 0.012 e 0.76 40 ( 1.60 0.40 ( 0.91 to 0.08); to p 0.11); = 0.075 p = 0.123 0.67 ( 1.01 0.34 ( 0.50 to 0.33); to 0.19); p < 0.001 p < 0.001 0.65 ( 0.96 0.27 ( 1.15 to 0.34); to 0.60); p < 0.001 p = 0.543 0.58 ( 0.76 0.26 ( 0.65 to 0.41); to 0.13); p < 0.001 p = 0.187 3.9 0.54 ( 0.89 0.24 ( 1.41 to 0.19); to 0.93); p = 0.003 p = 0.689 0.53 ( 0.92 to 0.15); p = 0.007 4 2 0 2 Mean. Treatment, mg Trospium chloride 40 0.24 ( 0.39 to 0.08); p = 0.002 E U R O E A U R O O G Y X X X ( 2 0 1 2 ) X X X X X X 9 95% confidence interval. YÖVIRTSAAMISKERRAT Fig. 2 Reductions of micturitions per 24 h compared with placebo (red line), including 32 020 patients. IR = immediate release; ER = extended rele TS = transdermal system. Solifenacin 10 0.17 ( 0.25 to 0.08); p < 0.001 be 0.5 (1/2), and so on. For each outcome and per treatment, were set at 1. Each of the standardized efficacy param Fesoterodine 8 0.14 ( 0.23 to 0.05); p = 0.002 the efficacy was standardized with the mean of all reported was multiplied by the inverse of the relevance ranking outcomes. Treatments without efficacy data for an outcome summarized per treatment, thus generating an effi Fesoterodine 4 0.13 ( 0.27 to 0.00); p = 0.058 Treatment, mg ropiverine IR 20 Solifenacin 10 0.12 ( 0.28 to 0.03); p = 0.111 0.70( 0.90 to 0.51); p < 0.001 Oxybutynin Oxybutynin TS 3.9ER 10 0.11 ( 0.63 0.70 to 0.41); ( 1.10 p = to 0.680 0.30); p = 0.001 ropiverine ER 30 0.69 ( 1.20 to 0.17); p = 0.009 Solifenacin 5 0.67 ( 0.98 to 0.36); p < 0.001 Solifenacin ropiverine 5 IR 45 0.10 ( 0.23 0.59 to 0.03); ( 1.34 p = 0.119 to 0.15); p = 0.116 Oxybutynin IR 15 0.50 ( 1.01 to 0.02); p = 0.059 Oxybutynin Oxybutynin topical gel TS 3.9 0.1 ( 0.28 0.45 to 0.08); ( 0.97 p = 0.282 to 0.06); p = 0.084 Solifenacin 2.5 0.45 ( 1.56 to 0.65); p = 0.422 ropiverine IR 30 0.43 ( 0.90 to 0.04); p = 0.075 Tolterodine ER 4 0.09 ( 0.17 to 0.01); p = 0.035 ropiverine IR 20 0.41 ( 0.84 to 0.03); p = 0.069 Trospium chloride 40 0.40 ( 0.94 to 0.14); p = 0.147 Tolterodine Solifenacin IR 4 20 0.04 ( 0.35 0.37 to 0.27); ( 1.55 p = 0.799 to 0.80); p = 0.535 Tolterodine ER 4 0.36 ( 0.55 to 0.17); p < 0.001 Tolterodine IR 8 0.25 ( 1.65 to 1.15); 1 p = 0.730.5 0.5 1

Hoitoon!sitoutuminen!(adherenssi)!yliak<ivisen! rakon!lääkkeisiin!(an<kolinergit)!on!alhainen! Comparing Adherence and ersistence Across 6 Chronic Medication Classes FIGURE 4 Time to iscontinuation a of 6 Chronic Therapy Classes, Allowing for 90-ay Treatment Gap 100% 90% 80% 70% ercent persistent 60% 50% 40% 30% 20% Oral antidiabetics ARBs Statins Bisphosphonates rostaglandins 10% OAB medications 0% 0 30 60 90 120 150 180 b 210 240 270 300 330 360 390 420 450 480 510 540 570 600 630 660 690 720 ays a iscontinuation rostaglandins was defined as the end Statins of days supplied Bisphosphonates for an index medication pharmacy Oral antidiabetics claim immediately preceding ARBs a 90-day OAB gap medications in therapy. A minimum of 12 months (maximum 24 months) continuous eligibility following the index date (day 0) was required. Beginning at day 390, the denominator for the calculation consisted of all remaining eligible patients with continuous enrollment through the end of the 30-day interval. atients with continuous enrollment ending between day 360 and day 720 were censored at the point of their cessation of benefits. b Using the 90-day gap, 6-month persistence rates were prostaglandin analogs 57%, statins 62%, bisphosphonates 62%, oral antidiabetics 72%, ARBs 69%, and OAB medications 32%. ARB = angiotensin II receptor blocker; OAB = overactive bladder. Yeaw ym. J Manag Care harm 2009;15:728

and urinary incontinence is known for its high incidence of adverse events and henceforth poor adherence and persistence. o systematic review of this has been published to date. Hoitoon!sitoutuminen:!systemaaKnen!katsaus! persistence-rates are usually very poor; see the graphs. This systematic review aims to review long-term (>6 months) adherence of antimuscarinic drugs in daily clinical practice. Moreover, it tries to identify risk factors for discontinuation, which could be of aid for physicians prescribing these drugs. were read. Fifteen studies were eventually included, containing 191,726 unique patients; mean age was 70.4 years. Regardless of which specific antimuscarinic drug is studied, A number of risk factors for discontinuation could be identified. The three most important of these are younger age, use of oxybutynin and the use of IR-formulations. It was noticeable that definitions used varied widely between the various studies, rendering a good meta-analysis impossible. STUY ESIG, MATERIAS A METHOS This systematic review was done according to RISMA-guidelines. A systematic search was performed on ecember 28, 2012 on ubmed (MEIE) and Embase, using synonyms for incontinence, overactive bladder and antimuscarinics, combined Veenboer with & synonyms Bosch. J for Urol medication-adherence. 2014;191:1003 and Only Veenboer English & papers Bosch. from eurourol the last Urodyn 10 years 2013;32:576 were taken into

Yleisimmät!syyt!lääkityksen!lope=amiseen!! Syy!!(%)! Ei!tehonnut!odotusten!mukaises7! 611!(46.2)! Vaihtoi!toiseen!lääkkeeseen! 332!(25.1)! Oppi!elämään!ilman!lääkitystä! 308!(23.3)! Oli!sivuvaikutuksia! 279!(21.1)! Benner ym. BJU Int 2010;105:1276

Yliak<ivisen!rakon!oireiden!! ikävakioitu!vallitsevuus! Virtsaamispakko ilman pakkokarkailua (ympyrä) Virtsaamispakko pakkokarkailun kanssa (soikio) Tihentynyt virtsaamistarve (>8) Yövirtsaaminen (>1) Virtsaamispakko Virtsaamispakko 3.3 2.4 2.2 0.9 1.0 0.4 0.3 Yövirtsaaminen 7.0 0.5 0.1 0.7 0.1 0.6 Tihentynyt virtsaamistarve 1.1 2.2 Yövirtsaaminen 6.6 1.4 0.7 1.0 1.4 Tihentynyt virtsaamistarve 4.8 MIEHET AISET Tikkinen ym. os One 2007;2:e195.

! OAB!is!misleading!because!it!makes!it!too! easy!for!clinicians!to!feel!they!have!made! a!diagnosis!when!they!have!not.!in!so! doing,!it!curtails!further!thinking!and!does! not!promote!the!scien7fic!pursuit!of!fact.!!orman-r.-zinner.-eurourol$urodyn$2011-

Amerikan!urologiyhdistyksen!(AUA/ SUFU)!yliak<ivisen!rakon!hoitosuositus! Verkossa!osoiZeessa:!!hZp://www.auanet.org/common/pdf/educa7on/clinical guidance/overac7vebladder.pdf!!

!! A!greater!danger!is!in!simply!lumping! symptoms!together!and!giving!them!a!new! label.!a!wholly!false!concept!ensues:!that!the! diagnos7c!label,!ooen!glorified!by!the!term! syndrome,!represents!a!new!disease.!this! stul7fies!further!thought!and!may!inhibit! research!and!inves7ga7on!of!the!ae7ology! because!doctors!commonly!regard!the! syndrome!(diagnosis)!as!a!disease.!!j-m-s-earce.-ract$eurol$2011-

Avaintekijät!sairauksien! markkinoinnissa! arannusehdotukset! 1.$ Taudin $vallitsevuuden$(prevalenssi)$liioi<elu- uodaan!laaja!sairauden! määritelmä! Julkaistaan!suuria! esiintyvyyslukuja! erehdy!määritelmään!ja! arvioi!sen!asianmukaisuus!/! tarkkuus! Kysy:! Onko!tutkimusjoukko! väestöä!edustava?"! Hämärretään!vakavan!ja! lievän!ero! Ota!selvää! taudin!kirjosta! Woloshin & Schwartz. os Med 2006:3:e170

Table 3 Overview of published population-based studies assessing the prevalence of overactive bladder in both sexes (ubmed-indexed English-language articles before January 2011) European [5] USA [7] Canada [31] Japan [32] Brazil [33] Taiwan [34] International [6] Telephone interview Telephone interview Mailed questionnaire ot reported Questionnaire administered Telephone registry Telephone registry ot reported ot reported opulation registry Telephone registry ata collection method Telephone/ Telephone interview in-person interview a by a nurse Sample source Telephone registry/ electoral census a Respondents 16 776 5204 3249 4570 913 1921 19 165 Response proportion, % ot reported 44.5 b 43.4 c 45.3 ot reported 67.0 33.0 Age range, yr 40 to 75 18 to 75 35 to 75 40 100 15 55 30 79 18 to 70 2002 ICS consensus /A /A /A o Yes o Yes definition of OAB e efinition 1. of normal/ Tutkimuksissa /A tai /A niiden raportoinnissa /A oli /Apuutteita, joiden ot reported takia /A prevalenssi yleensä ot reported abnormal occurrence e Time period yliarvioitiin f ot definedtutkimuksissa: ast 4 wk ast month ast month ot defined ast 4 wk ot defined Exclusion criteria: Yes/o Yes/Yes o/o o/o Yes/Yes o/yes o/o UTI e /other revalence of OAB, % e 17 16 18 12 19 17 12 Authors disclosurea. Ikäjakauma This study was painottunut Study was Unrestricted vanhempiin grant from ihmisiin Editorial support(n=6, Funding 43%) not reported Funding not reported This study was of industry support funded by the supported by fizer Canada Inc. and was provided by funded by fizer Inc. b. Ei poissulkukriteereitä (n=7, harmacia ovartis harmaceutical 50%) fizer Inc. Corporation Corporation Canada Inc. Finland [4] Korea [35] Canada [36] USA [37] ortugal [38] International [25] Korea [39] ata collection method Mailed questionnaire Telephone interview Telephone interview Mailed questionnaire/ Telephone interview Web-based interview Telephone based telephone interview Sample source opulation registry Telephone registry Telephone registry Consumer panel Telephone registry Consumer/voter panels Telephone registry Respondents 3727 2005 1000 162 906 1934 30 000 2000 Response 2. proportion, Vain % viisi 62.4 tutkimusta 13.8 14:sta (36%) ot reported käytti ICS-määritelmää 62.7 59.6 49.5 d 22.1 Age range, yr 18 79 40 89 18 90 18 to 85 40 to 80 40 99 18 96 2002 ICS consensus Yes o o o o Yes Yes definition of OAB e efinition of normal/ Rarely Often /A /A /A /A Rarely Sometimes ot reported 3. 12/14 (86%) lääketeollisuuden tukemia (osa unrestricted ), 2/14 (14%) ei raportoinut abnormal occurrence e (Sometimes Often) Time period f ast 2 wk ast 4 wk ot defined ot defined ast 4 wk ast 4 wk ot defined rahoitustaan, 0/14 (0%) raportoi, että riippumattomalla rahoituksella toteutettuja Exclusion criteria: Yes/Yes o/o o/o o/o o/o Yes/Yes Yes/Yes UTI e /other revalence of OAB, % e 8 26 14 27 32 29 (or 8) 12 Authors disclosure of industry support Unrestricted grant from fizer Supported by the Korean Continence Society Johnson and Johnson Medical, Korea grant Janssen-Ortho Canada for an unrestricted grant to support this study. Supported by fizer Inc. Unrestricted funding from OM ortuguesa This research was supported by funding from fizer Inc. This study was funded by fizer Korea and Korean Continence Society. ICS = International Continence Society; OAB = overactive bladder; /A = not applicable; UTI = urinary tract infection a In the European study, in five of six countries, a telephone interview was used (excluding Spain, where direct interviews were conducted because of a lower proportion of households with telephones). The study sample was obtained from telephone number listings (except in Spain, where electoral census data were used). b Of 11 740 participants (17 231 households contacted), 5539 were considered ineligible. To calculate the response rate, the number of respondents was divided by the number of eligible participants (the former response rate). If the same proportion of nonparticipants as were ineligible among participants (47%) were also considered ineligible, the response rate was greater (the latter response rate). c Of 7487 individuals, 3239 completed the questionnaire (response proportion: 43.4%). d An invitation to complete an e-mail survey was sent to 88 150 members of the Internet-based panel. Of the members, 51 546 responded, but 7947 were excluded because of high rates of missing or inconsistent data or discontinuation of the survey. Finally, 30 000 participants were randomly selected from the pool of respondents with completed surveys. e Cutoff point (threshold) used for normal versus abnormal symptom occurrence; reviewed only for studies using the current ICS definition of OAB [1]. f c. Alhainen (tai ei-raportoitu) osallistumisaste (n=10, 71%) d. Oireiden yleisyyttä/vakavuutta ei huomioitu (n=12, 86%) The time period during which the symptoms occurred was sought. Vaughan ym. Eur Urol 2011;59:629

Avaintekijät!sairauksien! markkinoinnissa! arannusehdotukset! 2.$iagnosoin@in$kannustaminen- Korostetaan,!eZä!lääkärit! eivät!tunnista!tau7a! Kannustetaan!ihmisten! omaan!diagnos7soin7in! Tunnusta!ja!huomioi! ylidiagnos7ikan!(ja!ylihoidon)! ongelmat! Edistetään! 7etoisuuZa! kri7ikizä! Ota!selvää!onko!toiminta! teollisuuden!sponsoroimaa! Woloshin & Schwartz. os Med 2006:3:e170

www.yliak<ivinenrakko.fi!

Yliak<ivisen!rakon!ar<kkelien!raportoidut! rahoituslähteet!! Systemaa\set! katsaukset! Kaupallinen!tukija!(täysin!tai!osiZain)! Eikaupallinen!tukija!(sää7öt!ja!val7onhallinto)!ainoastaan! Ei!rahoitusta erustutkimus! Kliininen!tutkimus!! (ei!randomisoidut)! Epidemiologia! Randomisoidut! kokeet! 0%! 25%! 50%! 75%! 100%! Tikkinen & Auvinen. Eur Urol 2012:61:746

Raportoidut!kaupalliset!sidonnaisuudet! yliak<ivista!rakkoa!käsi=elevissä!ar<kkeleissa! erustutkimus! Kliininen!tutkimus!! (ei!randomisoidut)! Systemaa\set! katsaukset! Epidemiologia! Randomisoidut! kokeet! 0%! 25%! 50%! 75%! 100%! Tikkinen & Auvinen. Eur Urol 2012:61:746

Avaintekijät!sairauksien! markkinoinnissa! arannusehdotukset! 3.$Annetaan$ymmärtää,$e<ä$aina$kanna<aa$hoitaa- iioitellaan!lääkityksestä! aiheutuvia!hyötyjä! Vähätellään!hoidon!haiZa vaikutuksia! Objek7ivises7!raportoi! hyödyt,!tutkimusväestö!ja! virhelähteet! Huomioi!ja!selvitä! sivuvaikutukset! Kerrotaan,!eZä! pitkäaikaishoito!on! turvallista!ja!tehokasta! Muista,!eZä!tutkimukset! ovat!lyhytkestoisia! Woloshin & Schwartz. os Med 2006:3:e170

FIctutkimus! Breast cancer rostate cancer neumonia ung cancer Juvenile diabetes Myocardial infarction Schizophrenia HIV/AIS Malaria Adult-onset diabetes Osteoporosis Autism Fibromyalgia own syndrome Sleep apnea epression eafness Elevated blood pressure Hip fracture AH Irritable bowel syndrome Anorexia anic disorder Bulimia ersonality disorder Alcoholic liver cirrhosis actose intolerance Overactive urinary bladder Work exhaustion Chronic fatigue syndrome Age-related muscle loss Eye refractive error Elevated cholesterol Generalized anxiety d/o Alcoholism Infertility Tension headache Restless legs syndrome Insomnia ight-time urination Social anxiety disorder Erectile dysfunction rug addiction ental caries Gambling addiction remenstrual syndrome Female menopause Malnutrition Male menopause Obesity Absence of sexual desire remature ejaculation Motivational deficiency d/o Transsexualism Baldness Homosexuality roportions (division at 0.2, 0.4, 0.6, and 0.8) to the claim [This state of being] is a disease in laypeople (), doctors (), nurses () and parliament members (). ark green represents individuals who strongly agreed, light green those who agreed to some extent, yellow those who neither disagreed nor agreed, light red those who disagreed to some extent, and dark red color those who strongly disagreed with the claim. States of being are ordered by proportion of laypeople considering them as a disease (those individuals who either strongly agreed or agreed to some extent). /o refers to disorder. Grief Ageing Smoking Wrinkles Tikkinen ym. BMJ Open 2012;2:e001632