Medical College of Pennsylvania and Hahnemann University. I. Potros, MD: "Buy cheap Finasteride - Proven Finasteride OTC".
Arterioscler XIa and murine carotid artery and middle cerebral artery thrombosis discount finasteride hair loss cure breakthrough. Liu Q finasteride 1 mg free shipping hair loss medication results, Bethune C order finasteride no prescription hair loss cure news 2014, Dessouki E buy finasteride 5 mg on line hair loss in men rain, Grundy J, Monia BP, Bhanot S. Factor XI regulates ISIS-FXIRx, a novel and speciﬁc antisense inhibitor of factor XI, caused pathological thrombus formation on acutely ruptured atherosclerotic signiﬁcant reduction in FXI antigen and activity and increased aPTT plaques. Effects of factor XI deﬁciency on Annual Meeting Abstracts). Synthesis, SAR exploration, and anti-human factor XI antibodies prevent cessation of blood ﬂow in a X-ray crystal structures of factor XIa inhibitors containing an alpha- murine venous thrombosis model. Defective thrombus formation factor XIa inhibitor produces antithrombotic efﬁcacy with minimal bleeding time prolongation in rabbits. Effects of plasma kallikrein potent and selective factor XIa inhibitors. Al-Horani RA, Ponnusamy P, Mehta AY, Gailani D, Desai UR. Deletion of murine pentagalloylglucoside is a potent, allosteric, and selective inhibitor of kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays factor XIa. Karuturi R, Al-Horani RA, Mehta SC, Gailani D, Desai UR. Kininogen deﬁciency protects from of allosteric modulators of factor XIa by targeting hydrophobic domains ischemic neurodegeneration in mice by reducing thrombosis, blood- adjacent to its heparin-binding site. Factor XI contributes to recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus propagation on injured neointima of the rabbit iliac artery. Factor XIIa inhibition by Infestin-4: in jugular vein thrombolysis by neutralization of factor XI. In vivo vitro model of action and in vivo antithrombotic beneﬁt. Thromb evidence for a role of factor XI as an anti-ﬁbrinolytic factor. Inhibition of warfarin in patients with mechanical heart valves. Dabigatran and mechanical heart valves–not as easy as we 464-470. Mega JL, Braunwald E, Wiviott SD, et al; ATLAS ACS 2–TIMI 51 biological evaluation of aryl boronic acids as potential inhibitors of Investigators. Rivaroxaban in patients with a recent acute coronary factor XIa. Tricoci P, Huang Z, Held C, et al; TRACER Investigators. Thrombin- product with selective recognition and irreversible inhibition of factor receptor antagonist vorapaxar in acute coronary syndromes. Morrow DA, Braunwald E, Bonaca MP, et al; TRA 2P–TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary XIa anticoagulant from the salivary gland of the vampire bat (Desmodus prevention of atherothrombotic events. Baeriswyl V, Calzavarini S, Gerschheimer C, Diderich P, Angelillo- formation following FeCl3-induced injury of the carotid artery in the Scherrer A, Heinis C. Development of a selective peptide macrocycle mouse. Effects of factor IX or factor XI antithrombotic therapy. Woodruff RS, Xu Y, Layzer J, Wu W, Ogletree ML, Sullenger BA. Inhibiting the intrinsic pathway of coagulation with a factor XII- 41. XII provides protection from pathological thrombosis in cerebral 59. Location of the disulﬁde bonds ischemia without interfering with hemostasis. Key1 1Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC Currently available evidence supports the contention that elevated levels of factor XI (fXI) are associated with a greater risk of venous thromboembolism and ischemic stroke, but, less convincingly, with myocardial infarction. Conversely, reduced plasma levels of fXI seem to offer some protection from venous thromboembolism and stroke, but not myocardial infarction. Factor XI-deﬁcient patients are at risk for certain types of bleeding, particularly posttraumatic hemorrhage on mucosal surfaces where there is a high endogenous ﬁbrinolytic activity. In contrast, the situation with fXII in human thrombosis remains enigmatic. Deﬁciency of fXII is clearly not associated with any bleeding risk, but neither does it seem to be protective against thrombosis. The longstanding debate as to whether partial fXII deﬁciency represents a risk factor for thrombosis remains unresolved, with seemingly conﬂicting results depending on study design, type of assay used, and analyte evaluated. The possibility that elevated fXII levels represent a risk factor for thrombosis is not borne out in the literature. The fact ● To understand that high levels of factor XI are associated with that even severe fXII deﬁciency is not associated with bleeding, thrombosis, but that the relationship between factor XII and whereas fXI deﬁciency of a more moderate degree is, provides thrombosis is not established compelling evidence for the existence of an alternative mechanism by which fXI is activated during physiological hemostasis. The discovery Introduction that thrombin fulﬁlls this role was a milestone observation and led to a 1953 was a landmark year in the history of the intrinsic pathway of revised coagulation schematic in which hemostasis is initiated by tissue factor/fVIIa, with thrombin providing feedback activation of fXI. Rosenthal et al described a factor that, when deﬁcient, was associated with a familial bleeding disorder. He noted Such a revised model adequately addresses the dichotomous bleeding that both sexes could be affected and that the abnormal clotting phenotypes in fXI and fXII deﬁciencies. In the In addition to its procoagulant function in the activation of fIX, fXIa same year, Brinkhous et al invented the partial thromboplastin time contributes to hemostasis by down-regulating ﬁbrinolysis. This role (PTT) test,2 which was later modiﬁed by Rapaport to include a is mediated by activation of thrombin-activatable ﬁbrinolysis inhib- kaolin activation step, which became the basis of today’s activated itor (TAFI), also known as plasma carboxypeptidase U. It makes intuitive sense, Rosenthal’s cases, these individuals had no abnormal bleeding therefore, that the typical bleeding manifestations in fXI-deﬁcient history and the discovery of their defect was entirely serendipitous patients tend to be more pronounced at sites of enhanced ﬁbrinolytic during presurgical screening. This defect was also shown to be activity, such as in the nasopharyngeal or genitourinary tracts. Further milestones, including the ous intraarticular or intramuscular bleeding that is seen in patients discovery of the last remaining “major” procoagulant, namely fX with hemophilia. Factor XII also participates in ﬁbrinolysis; fXIIa, (“Stuart Prower factor”) in 1956,5 laid the groundwork for the via activation of pre-kallikrein, activates plasminogen and pro- waterfall or cascade models of blood coagulation proposed by 2 urokinase, and thus has a seemingly paradoxical role in promoting groups on either side of the Atlantic. The autoactivation of fXII after several other case reports and series of thrombotic events in contact with negatively charged surfaces was proposed to be the fXII-deﬁcient subjects,11 led to a view that fXII deﬁciency is a initiating event that preceded activation of fXI, thereby providing an hypercoagulable state in humans.
Results and Conclusion Overall purchase generic finasteride hair loss forums, targeted immune modulators are highly effective medications for the treatment of rheumatoid arthritis order finasteride 5mg on-line hair loss in men 70s, juvenile idiopathic arthritis order finasteride 1mg on-line hair loss in men 4x100, ankylosing spondylitis discount finasteride hair loss causes, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis that substantially improve the burden of disease and are generally safe for short-term treatment. For rheumatoid arthritis, low-and moderate-strength evidence indicated that some targeted immune modulators are more efficacious than others. These results were based on three head-to-head trials, several large observational studies, and indirect comparisons of placebo- controlled trials. The evidence is currently insufficient to reliably determine the comparative effectiveness for other indications and in subgroups. Low-strength evidence indicated that serious infections are less common with abatacept than the other drugs and that the rate of adverse events is greater with infliximab than adalimumab or etanercept. Likewise, more patients receiving infliximab withdrew due to adverse events than abatacept, adalimumab, etanercept, and golimumab. Infusion or allergic reactions contributed to the difference in risk. Targeted immune modulators 3 of 195 Final Update 3 Report Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION.......................................................................................................................... American College of Rheumatology - European League Against Rheumatism classification criteria for rheumatoid arthritis (revised 2010)............................................................................................ CASPAR classification criteria for psoriatic arthritis (2006)......................................................... Definitions of the grades of the overall strength of evidence..................................................... Summary of head-to-head studies in adult patients with rheumatoid arthritis........................... Characteristics and results of studies conducting indirect comparisons.................................... Studies included for general efficacy in rheumatoid arthritis...................................................... Summary of efficacy trials in patients with juvenile idiopathic arthritis....................................... Summary of efficacy trials in adult patients with ankylosing spondylitis.................................. Summary of efficacy trials in adult patients with psoriatic arthritis........................................... Characteristics and results of studies conducting direct and adjusted-indirect comparisons.. Summary of studies in adult patients with Crohn’s disease..................................................... Summary of efficacy trials in adult patients with ulcerative colitis............................................ Summary of efficacy trials in patients with plaque psoriasis.................................................... Summary of efficacy trials in children with plaque psoriasis.................................................... Statistically significant indirect comparisons: Serious Infection............................................... Statistically significant differences in serious adverse events.................................................. Summary of studies with direct comparisons of adverse events in adults receiving targeted immune modulators.................................................................................................................................. Adjusted indirect comparisons of targeted immune modulators for American College of Rheumatology 50 response...................................................................................................................... Adjusted indirect comparisons of etanercept including the TEMPO study for American College of Rheumatology 50 response................................................................................................................. Instruments used to measure outcomes in trials involving targeted immune modulators. Targeted immune modulators 7 of 195 Final Update 3 Report Drug Effectiveness Review Project Acknowledgments We thank Evelyn Auer and Michaela Strobelberger for administrative assistance and Leah Williams, our publications editor, for putting this report into its present form for you to read. Clinical Advisory Group We extend our appreciation to the clinical advisor listed below for their thoughtful advice and input during our research process. Paula Morris, MD University of Arkansas for Medical Sciences Suggested citation for this report Thaler KJ, Gartlehner G, Kien C, Van Noord MG, Thakurta S, Wines RCM, Hansen RA, McDonagh MS. Prepared by the RTI-UNC Evidence-based Practice Center for the Drug Effectiveness Review Project. Hansen, PharmD, PhD Beth Jonas, MD Update 1 authors Gerald Gartlehner, MD, MPH Richard A. Hansen, PhD Patricia Thieda, MA Beth Jonas, MD Kathleen N. Lohr, PhD Tim Carey, MD, MPH Original report authors Gerald Gartlehner, MD, MPH Richard A. Hansen, PhD Patricia Thieda, MA Beth Jonas, MD Kathleen N. Lohr, PhD Tim Carey, MD, MPH Funding The Drug Effectiveness Review Project, composed of 12 organizations including 11 State Medicaid agencies, and the Canadian Agency for Drugs and Technology in Health commissioned and funded for this report. These organizations selected the topic of the report and had input into its Key Questions. The content and conclusions of the report were entirely determined by the Evidence-based Practice Center researchers. The authors of this report have no financial interest in any company that makes or distributes the products reviewed in this report. Targeted immune modulators 8 of 195 Final Update 3 Report Drug Effectiveness Review Project INTRODUCTION Targeted immune modulators, commonly referred to as biological response modifiers or simply biologics, are a relatively new category of medications used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ulcerative colitis. The US Food and Drug Administration approved the first of the biologics (infliximab) in 1998 and approved 12 additional agents since that time for treating various rheumatic conditions, inflammatory bowel diseases, and plaque psoriasis: etanercept (1998), anakinra (2001), adalimumab (2002), alefacept (2003), efalizumab (2003), abatacept (2005), rituximab (2006), natalizumab (2008), certolizumab pegol (2008), golimumab (2009), ustekinumab (2009), and tocilizumab (2010). Table 1 summarizes currently approved biologics in the United States, including trade name, manufacturer, route of administration, approved (labeled) uses, and dosage. Included interventions Generic Trade name Mechanism name Manufacturer of action Indication Dosage and administration approved by the FDA Intravenous infusion dosed according to body weight (<60 kg = 500 mg; 60-100 kg = 750 mg; >100 kg = 1000 mg); dose repeated at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter. Following single intravenous loading dose according to body weight specified above, the first 125 mg subcutaneous injection within 1 day, followed by 125 mg Rheumatoid once weekly. Juvenile rheumatoid a arthritis (6 See Canadian product label years and older) Juvenile idiopathic 10 mg/kg for patients <75 kg; adults schedule for arthritis (6 patients >75kg (maximum dose 1000 mg) on weeks 0, 2, years and and 4 and then every 4 weeks thereafter. Two weeks later (Day 29) begin a maintenance dose of 40 mg every other week. Plaque 80 mg initial subcutaneous dose followed by 40 mg psoriasis every other week starting 1 week after initial dose.
Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function buy finasteride 1 mg mastercard hair loss hypothyroidism. Growth hormone resurrects adult human thymus during HIV-1 infection buy finasteride 1 mg fast delivery hair loss cure philippines. J Clin Invest 2008; Thiebaut R order finasteride 5 mg on line hair loss cure stem cell 2013, Morlat P generic 5 mg finasteride hair loss cure news 2013, Jacqmin-Gadda H, et al. Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitors to regimens containing NRTI plus non-NRTI or only NRTI. BMC Infect Dis 2011, 11:23 van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F; ATHENA national observational cohort study. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individu- als. Clinical outcome of HIV-infected patients with discordant virologi- cal and immunological response to antiretroviral therapy. Treatment goal: “HIV cure” GEORG BEHRENS, CHRISTIAN HOFFMANN The cure of HIV-infected patients remains the holy grail of HIV medicine. With the introduction of combination ART it has been calculated that the calculated time to eradication of all reservoirs is 70 years. Thus, it is clear that strategies beyond the current ART regimen will be necessary. Many researchers share the opinion that a cure has to be the major goal for the future. The cure of the so-called Berlin patient Timothy Brown, published in 2008, shows that a cure is at least theoretically possible. Brown had suffered from acute myeloid leukemia and underwent allogeneic stem cell transplantation. The healthy stem cell donor was homozygous for the 32 mutation, a genetic defect leading to the absence of CCR5 co-receptor from his cells – after the transplant the viral load of in the Berlin patient (which was very high before ART initiation) has disappeared for at least four years (Hütter 2009, Allers 2011, Symons 2014). The virus was undetectable in the blood, in the lymph nodes and in the intestinal mucosa (Yukl 2013), suggesting that targeted CCR5 disruption can lead to an HIV cure. There is no doubt that in clini- cal practice, an allogeneic stem cell transplant is not an appropriate way for a HIV cure (Cillo 2013). It is not only complicated and expensive, but also highly risky (mortality up to 30%), making this approach not very practical (Zhou 2013). However, although not reproducible until today, the case of the Berlin patient stirred hope for future academic purposes. Eradication of all viruses from the body would be the definitive cure. Much would have been achieved if the immune system is able to control HIV without help of medication – i. This is why a difference is being made today between a “sterilizing cure” and “functional cure” (Reviews: Richman 2009, Lewin 2011). A functional cure is achieved in the so called “post treatment controllers” (PTC), in whom viremia remained controlled for several years after the interruption of ART. Currently at least four strategies are being pursued and partly combined. Improvement of the HIV-specific immune response and 4. Attempts to make cells more resistant against HIV infection. A few patients have already reached functional cure. These so-called “elite con- trollers”, some found in most large HIV centers, have normal CD4 T cells for many years and even more impressive, a viral load below the limit of detection without therapy. Only when investigating with ultrasensitive methods or examining the lymph nodes can a relatively tiny amount of virus be found. Co-receptor defects explain only a few of the cases, and efficient antiviral immunity capable of con- trolling HIV reaction was observed occasionally (Smith 2015) (see Pathogenesis). However, despite maintaining very low levels of plasma viremia, elite controllers have elevated immune activation and accelerated atherosclerosis. In a prospective trial, controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART (Hatano 2013). Moreover, markers of T cell activa- tion/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of “elite” controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These observa- tions raise the question whether a functional cure is comparable to well-tolerated ART and whether the degree of HIV suppression in elite controllers is equivalent to that achieved by ART when it comes to clinical outcomes. Goals and principles of therapy 159 Can (very) early ART lead to a cure? In 2013, the case of the perinatal infected “Mississippi Baby” gained worldwide attrac- tion. This infant had been antiretrovirally treated only 31 hours after birth (Persaud 2013). The baseline viral load of 19,812 copies/ml felt down to 265 copies/ml at day 19 and was then undetectable for 18 months. The baby was then lost to the health care system for the next six months. Unexpectedly, the viral suppression remained undetectable when tested for HIV upon return. More than two years this girl had no signs of the virus in her blood despite cessation of treatment. An ultrasensitive assay revealed 4 copies HIV-DNA/million PBMCs but no HIV-specific immune responses. Protective HLA types as seen in elite controllers were not observed. The finding encouraged scientists hoping to find a way to save children from a lifetime of ART. However, the virus resurfaced in the patient 27 months after ART stopped (Ledford 2014). It became obvious that the “post-treatment control” had only been transient. Moreover, similar pediatric cases were published in which virologic rebound occurred within days of discontinuation of ART, despite immediate treatment after delivery (Butler 2015). Also in 2013, PTC cases had been published from France (Sáez-Cirión 2013).
R andom iz ed controlled trials ofduodenalulcertreatm ent:Protonpum pinh ibitorcom pared with protonpum p inh ibitor A uth or A ge finasteride 5 mg without a prescription hair loss cure how long,G ender 5mg finasteride with amex hair loss in men zoot,R ace Y ear O th erPopulation Setting C h aracteristics Intervention C ontrol N um ber E kstrom M eanage55 L ansopraz ole30m g O m epraz ole20 279enrolled(143 1995 47% sm okers onceaday x 4weeks m g aday x 4 lansopraz ole purchase 1mg finasteride with mastercard hair loss talk forum,136 Sweden 43% alcoholusers weeks om epraz ole) M ulticenter 10% N SAID users F anti M edianage47 L ansopraz ole30m g O m epraz ole20 43enrolled(22 2001 lansopraz oleand48 onceaday x 4weeks m g aday x 4 lansopraz oleand21 Italy om epraz ole Plusclarithrom y cin weeks om epraz ole) Singlecenter 68% m ale 500andtinidaz ole1 Plus 56% sm okers gm x 7day s clarithrom y cin500 54% alcoholusers andtinidaz ole1 gm x 7day s J i M eanage50 5 mg finasteride overnight delivery hair loss in men going. R andom iz ed controlled trials ofduodenalulcertreatm ent:Protonpum pinh ibitorcom pared with protonpum p inh ibitor A uth or Y ear Setting O utcom es R eported (R esults) N um berofA dverse Effects Q uality R ating E kstrom H ealingrates: 68adverseeventsoccurredin57patients(23patientstaking F air 1995 2 weeks: lansopraz ole,34taking om epraz ole). A statistically significantdifferencewasfoundin 4 weeks: them eanchangeinAL AT concentration,butthechangewas Endo:97. At4weeksthe reductioninsy m ptom sfavoredlansopraz ole,p = 0. A ntacids:nodifferencefound F anti H ealingrates: “M ildandself-lim iting” Totalnum bernotreported F air 2001 8 weeks:100% both groups 1lansopraz olestom atitisand1om epraz olem ilddiarrhea Italy Symptoms:”rapidclinicalresponsewith disappearanceof sy m ptom s Singlecenter inboth groups” J i R emainingratio ofpepticulcers after1 week Threenon-seriousadverseeventsintheom epraz ole F air-nom ethods 2006 R abepraz ole45. R andom iz ed controlled trials ofduodenalulcertreatm ent:Protonpum pinh ibitorcom pared with protonpum p inh ibitor A uth or A ge,G ender,R ace Y ear O th erPopulation Setting C h aracteristics Intervention C ontrol N um ber Subei M eanage(SD ) 40. R andom iz ed controlled trials ofduodenalulcertreatm ent:Protonpum pinh ibitorcom pared with protonpum p inh ibitor A uth or Y ear Setting O utcom es R eported (R esults) N um berofA dverse Effects Q uality R ating Subei H ealingrates at4 weeks E som epraz olevs.. M ostfrequenttasteperversion, Hungary ,Poland, (ITT) 91% esom epraz ole,92% om epraz ole diarrhea,loosestools. N oclinically relevanttrendsfor (ITT) 86% esom epraz ole,88% om epraz ole changesinlaboratory safety variables. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear A ge,G ender,R ace,O th erPopulation N um berScreened/Eligible/ Setting C h aracteristics Interventions C ontrol Enrolled D obrilla M eanage45(range18-69) L ansopraz ole15or30m g O m epraz ole20m g daily x 12 M aintenancephase:243enrolled 1999 66% m ale daily x 12m onths m onths (164lansopraz ole,79om epraz ole) Italy 52% sm okers M ulticenter 34% alcoholuse 90% Helicobacterpy loripositive 21% N SAID users;80% treatedwith lansopraz ole x 8-16weeksforacuteulcer;95% H-2antagonist resistantacuteulcer L anz a M eanage43 L ansopraz ole15m g once Placebooncedaily x 12 186enrolled(88placebo,92 1997 63% m ale daily x 12m onthsoruntil m onthsoruntilulcer lansopraz ole) U SA 76% Caucasian ulcerrecurrence recurrence M ulticenter 48% sm okers 56% alcoholusers Proton pump inhibitors Page 143 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 8. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear Q uality Setting O utcom es R eported N um berofA dverse Effects R ating C om m ents D obrilla M aintenance:(unclearanalysis) Serum gastrinlevelswereelevatedinboth groups F air/poor If assignedto 1999 6 month s: at4weeks(increaseof 23. At6m onthsfollow up allvalueswere form aintenance 6 month s:0% relapseinallgroups returning tobaseline. N o U SA (ITT) 62% placebo,27% lansopraz ole significantdifferencesbetweengroups. Serum M ulticenter (E ndo) 61% placebo,26% lansopraz ole gastrinlevelsweresignificantly higherin Symptoms: lansopraz olegroup thanplacebo,m edian92pg. Valuesreachedaplateau both groups afteronem onth of treatm entandreturnedto Asy m ptom atic during 9-12m onths:75% lansopraz ole, baselineonem onth aftertreatm entstopped. Proton pump inhibitors Page 144 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 8. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear A ge,G ender,R ace,O th erPopulation N um berScreened/Eligible/ Setting C h aracteristics Interventions C ontrol Enrolled K ovacs M eanage57placebo, L ansopraz ole15or30m g Placebooncedaily forup to 19placebo,18lansopraz ole15m g, 1999 54lansopraz ole15m g,47lansopraz ole30m g oncedaily forup to12 12m onths 19lansopraz ole30m g,other3not U SA 88% m ale m onths reported) M ulticenter 57% sm okers 39% alcoholusers Proton pump inhibitors Page 145 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 8. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear Q uality Setting O utcom es R eported N um berofA dverse Effects R ating C om m ents K ovacs R ecurrence: 40patientsreportedadverseevents(11placebo, F air Priortoenrollm ent, 1999 1 month :27% placebo,13% lansopraz ole15m g,6% 15lansopraz ole15m g,14lansopraz ole30m g). Allpatientsonplaceboex periencedrecurrenceor W ithdrawalsduetoadverseevents:2placebo,3 withdrew from study by 6m onths. N o Symptoms: significantchangesfrom baselineonlabs, Symptom free at phy sicalex am ,orE CG. Serum gastrinlevels 12 month s:82% lansopraz ole15m g,76% increasedsignificantly inboth lansopraz ole lansopraz ole30m g groupscom paredtoplacebo(P<0. Allpatientsonplaceboex periencedsy m ptom s, E levationsoccurredwithin1m onth of starting recurrenceorwithdrew from study by 6m onths study. Allreturnedtobaselinewithin1m onth of stopping study drug. ChangesinG rim elius- positive Proton pump inhibitors Page 146 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 8. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear A ge,G ender,R ace,O th erPopulation N um berScreened/Eligible/ Setting C h aracteristics Interventions C ontrol Enrolled R usso M eanage44 If lansopraz ole30m g If rabepraz oleduring healing Healing:132enrolled(68 1997 68% m ale during healing trial: trial:ranitidineorplacebo150 lansopraz ole,64ranitidine) Italy 55% sm okers(43% > 15/day ) lansopraz ole15m g or m g oncedaily x 12m onthsor M aintenance:108enrolled(30 M ulticenter 32% alcoholusers placebooncedaily x 12 recurrence (lansopraz ole30m g/lansopraz ole H. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear Q uality Setting O utcom es R eported N um berofA dverse Effects R ating C om m ents R usso R ecurrence:(ITT) M aintenance: H ealing: Healing:lansopraz ole30 1997 3 month s:7% (lansopraz ole/lansopraz ole),14% R eportedas3% (lansopraz ole/lansopraz ole), G ood/F air m g orranitidine. Italy (lansopraz ole/placebo),8% (ranitidine/ranitidine),27% 18% (lansopraz ole/placebo),0% M aintenance: baselineinform ationon M ulticenter (ranitidine/placebo) (ranitidine/ranitidine); F air/Poor m aintenancephase 6 month s:17% (lansopraz ole/lansopraz ole),32% (ranitidine/placebo) notreported participantsnotreported. R esultsfor (lansopraz ole/placebo),38% (ranitidine/ranitidine), sy m ptom sduring healing 50% (ranitidine/placebo) phasenotreported. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear A ge,G ender,R ace,O th erPopulation N um berScreened/Eligible/ Setting C h aracteristics Interventions C ontrol Enrolled G raham M eanage48om epraz ole,50ranitidine,47 N one N one 240enrolled(80% of om epraz ole, 1992 placebo 63% of ranitidineand27% of U SA % m ale:75% om epraz ole,67% ranitidine,69% placebopatientseligibleenrolled) M ulticenter placebo M eanindex ulcersiz ecim etidine: 0. Duodenalulcerrecurrence rates onm aintenance th erapy A uth or, Y ear Q uality Setting O utcom es R eported N um berofA dverse Effects R ating C om m ents G raham L ifetableanaly sisrelapserates:78% om epraz ole, N onereported F air F ollowup study of 1992 60% (ranitidine),50% placebo(N S) om epraz ole20m g vs U SA ranitidineorom epraz ole M ulticenter 20m g vsplacebo Proton pump inhibitors Page 150 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 9. R andom iz ed controlled trials ofgastriculcertreatm ent A ge,G ender,R ace, A uth or O th erPopulation N um berScreened/ Y ear C h aracter- Eligible/ Setting istics Interventions C ontrol Enrolled O utcom es R eported (R esults) D ekkers M eanage55 R abepraz ole20m g 20m g of 227enrolled H ealing rates by ITT: 1998 57% m ale oncedaily. Py loripositive stated,butassum edto 3 weeks:58% (r),63% (o) Ireland,N etherlands, 24% antaciduse be6weeksbasedon 6 weeks:93% (rando) Poland,Spain, 96% had> /= 0. R andom iz ed controlled trials ofgastriculcertreatm ent A uth or Y ear Setting N um berofA dverse Effects Q uality R ating D ekkers 60patientsreportedatleastoneadverseevent. Slightly elevatedcreatinephosphokinaseat6weeks Belgium ,E ngland, wasfoundin6(o) patients. Them eanelevationsinserum gastrinlevelsat6 G erm any ,Iceland, weekswere12. Ireland,N etherlands, Poland,Spain, Sweden M ulticenter Ando,2005 8adverseeventsreportedin5patients F air R :abdom inalpain,nausea,headaches O :diarrhea,abdom inalpain,nauseaflatulence,headache Proton pump inhibitors Page 152 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 9. R andom iz ed controlled trials ofgastriculcertreatm ent A ge,G ender,R ace, A uth or O th erPopulation N um berScreened/ Y ear C h aracter- Eligible/ Setting istics Interventions C ontrol Enrolled O utcom es R eported (R esults) F lorent1994 M eanage56 L ansopraz ole30m g 20m g of 126enrolled H ealing R ates by PP: F rance 64% m ale oncedaily om epraz ole 4 weeks:82% (l),68% (o) 49% sm okers 4to8weeks 8 weeks:93% (l),82% (o) PainR elief: Daytime:86% (l),60% (o) N octurnalpain: 100% (l),70% (o) Time to daytime painrelief: 6. After ranitidine) M aintenancestudy both gastric and healing: 58. R andom iz ed controlled trials ofgastriculcertreatm ent A uth or Y ear Setting N um berofA dverse Effects Q uality R ating F lorent1994 23adverseeventswerereported(8(l),15(o)). Them ostcom m onadverse Poor-openlabel,high drop-outrate, F rance eventwith L wasdiarrhea,andwasheadacheanddiarrheawith O. R andom iz ed controlled trials ofgastriculcertreatm ent A ge,G ender,R ace, A uth or O th erPopulation N um berScreened/ Y ear C h aracter- Eligible/ Setting istics Interventions C ontrol Enrolled O utcom es R eported (R esults) K ovacs M eanage58(pl),57 L ansopraz ole15or Placebooncedaily 52patientseligible, R ecurrence: 1999 (l15),58(l30) 30m g oncedaily forup forup to12 49enrolled m edian<2m onths(pl),> 12m onths(lgroups) U SA 85% m ale to12m onths(if m onths(if A t1 month :40% (pl),0% (l15),7% (l30) M ulticenter 67% sm okers recurrenceoccurred, recurrence 12 month s:0% (pl),17% (l15),7% (l30) (P<0. Proton pump inhibitors Page 155 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 9. R andom iz ed controlled trials ofgastriculcertreatm ent A uth or Y ear Setting N um berofA dverse Effects Q uality R ating K ovacs 39patientsreported1or> adverseeventsreported(13(pl),14(l15),12(l30), F air 1999 N S. Them ostcom m onadverseeventsthatwerepossibly orprobably related U SA tostudy drug werediarrhea(0%(pl),0% (l15),13. N oclinically significantlab changes,vitalsigns,orE CG seen. Proton pump inhibitors Page 156 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 9. R andom iz ed controlled trials ofgastriculcertreatm ent A ge,G ender,R ace, A uth or O th erPopulation N um berScreened/ Y ear C h aracter- Eligible/ Setting istics Interventions C ontrol Enrolled O utcom es R eported (R esults) CooperativeStudy M eanage:57(o),61 O m epraz ole40m g R anitidine150m g 46enrolled(21(o), H ealing (PP): 1990 (ran) oncedaily x 2to8 twicedaily x 2to8 25(ran)) 4 weeks:81% (o),58% (ran)(N S) U K 54% m ale weeks weeks 27enrolledin 8 weeks: 93% (o),87% (ran)(N S) M ulticenter 65% sm okers followup study (12 Painfree (baseline notreported) 74% alcoholusers (o),15(ran)) 2 weeks:53% (o),42% (ran)(N S) 4 weeks:73% (o),38% (ran)(N S) 8 weeks:50% (o),44% (ran) (N S) N ighttim epainat2weeks(o) <(r),datanotreported,(P<0. R andom iz ed controlled trials ofgastriculcertreatm ent A uth or Y ear Setting N um berofA dverse Effects Q uality R ating CooperativeStudy 1death judgedtobeunrelatedtostudy. U K M ulticenter Proton pump inhibitors Page 158 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 9. R andom iz ed controlled trials ofgastriculcertreatm ent A uth or Y ear Setting N um berofA dverse Effects Q uality R ating W alan 106patientsreportedadverseevents(34(o20),32(o40),40(ran)). Them ost G ood/F air 1989 com m onwereG I sy m ptom s,sim ilarinallgroups. N um berswithdrawnorlost Com m ent:Patientsenrolledin 13countries(prim arily tofollow up:21(o20),19(o40),22(ran) followup study notwelldescribed, E uropeanplus 3patientsdiedduring study (allon(o40)) of causesshowntobeunrelatedto attritionnotdescribed.