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Members of the Notch family are involved in the development of breast cancer in animal models and in humans. In young transgenic mice, expressing intracellular activated Notch1 (N1(IC)) in mammary cells, we found that CD24(+) CD29(high) progenitor cells had enhanced survival, and were expanded through a cyclin D1-dependent pathway. This expansion positively correlated with the later cyclin D1-dependent formation of basal-like ductal tumors. This expanded population exhibited abnormal differentiation skewed toward the basal cells, showed signs of pre-malignancy (low PTEN/p53 and high c-myc) and contained stem cells with impaired self-renewal in vivo, and more numerous multipotent, ductal-restricted progenitors. Our data suggest that N1(IC) can favor transformation of progenitor cells early in life through a cyclin D1-dependent pathway.

V532 Oph has been found to be a member of the rare, hydrogen-deficient R Coronae Borealis (RCB) stars from new photometric and spectroscopic data reported in this paper. The lightcurve of V532 Oph shows the sudden, deep, irregularly spaced declines characteristic of RCB stars. Its optical spectrum is typical of a warm (T(eff)~7000 K) RCB star, showing weak or absent hydrogen lines, the C2 Swan bands, and no evidence for 13C. In addition, the star shows small pulsations typical of an RCB star and an infrared excess due to circum- stellar dust. It also appears to be significantly reddened by foreground dust. The distance to V532 Oph is estimated to be 5.5-8.7 kpc. These new data show that this star was misclassified as an eclipsing binary in the General Catalog of Variable Stars. The new data presented here for V532 Oph reveal the power of high-quality, high-cadence all-sky photometric surveys, such as ASAS-3, to identify new RCB candidates on the basis of lightcurve data alone, now that they have been collecting data for durations sufficiently long to reveal multiple declines. Despite their small numbers, RCB stars may be of great importance in understanding the late stages of stellar evolution. In particular, their measured isotopic abundances imply that many, if not most, RCB stars are produced by WD mergers, which may be the low-mass counterparts of the more massive mergers thought to produce type Ia supernovae. Therefore, establishing the population of RCB stars in the Galaxy will help constrain the frequency of these WD mergers. Comment: 11 pages, 4 figures, PASP in press

OBJECTIVES: Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors. DESIGN: Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. SETTING: Mulago National Referral Hospital in Kampala, Uganda. SUBJECTS: Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log(10) increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β −0.42, 95% CI, −0.69 to −0.15, p = 0.002; children ≥ 5, β −0.39, 95% CI, −0.67 to −0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau). CONCLUSIONS: These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.

Abstract Background: The post-HERCULES trial (NCT02878603) evaluated long-term safety and efficacy of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura (aTTP; also known as immune-mediated TTP), and efficacy of repeated use of caplacizumab for aTTP recurrence. Methods: Patients who completed the HERCULES trial were invited to participate in the post-HERCULES study and attend twice-yearly visits for 3 years. In case of aTTP recurrence, patients could receive open-label (OL) caplacizumab with therapeutic plasma exchange (TPE) and immunosuppression (IST). Safety was assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences. TTP-related events (recurrence, mortality, or major thromboembolic events) were assessed in the efficacy ITO population. The ITO population (n=104) included all enrolled patients, grouped by whether they received caplacizumab during HERCULES (randomized or switched to OL after exacerbation). The efficacy ITO population (n=78) included those without aTTP recurrence during HERCULES or prior to the beginning of post-HERCULES. The recurrence population (n=19) included patients with ≥1 recurrence during post-HERCULES; the repeat-use population (n=9) was a subset treated at least twice with caplacizumab (received caplacizumab in HERCULES or treated twice in post-HERCULES). Pharmacodynamics and immunogenicity were assessed in the ITO population. The study was conducted in accordance with the Declaration of Helsinki. Results: Of 104 patients enrolled in post-HERCULES, 75 were treated with caplacizumab along with TPE+IST during HERCULES (caplacizumab group) and 29 were treated with TPE+IST only (placebo group). During the overall post-HERCULES study period, incidence of adverse events (AEs) and serious AEs was similar between the groups. In the ITO population, recurrence occurred in 11/75 patients (15%) in the caplacizumab group and 8/29 patients (28%) in the placebo group. In the efficacy ITO population, TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab versus 38% (11/29) randomized to placebo (Table 1). Prior rituximab use during HERCULES was similar in both groups (21/49 patients [43%] randomized to caplacizumab and 12/29 [41%] randomized to placebo). Incidence of recurrence by prior rituximab use (with vs without) was 10% (2/21) versus 7% (2/28) among patients randomized to caplacizumab, and 17% (2/12) versus 35% (6/17) among patients randomized to placebo. Of 19 patients with ≥1 recurrence, 13 were treated with caplacizumab and 6/13 received concomitant rituximab. Recurrences were resolved (12/13) or resolving (1/13) for all patients treated with caplacizumab, including 9 patients with repeat caplacizumab use. One patient who did not receive caplacizumab in either HERCULES or post-HERCULES died as an outcome of recurrence. Safety profile of caplacizumab for treatment of recurrence was consistent with that observed in HERCULES (Table 2) . The most common treatment-emergent AEs (TEAEs) with caplacizumab during the first recurrence (n=13) were headache and constipation (n=3 each). In the repeat-use population (n=9), bleeding events were reported in 5/9 patients (56%) for the first recurrence; 2 patients had a serious treatment-related TEAE of genitourinary or gastrointestinal bleeding; 2 patients had treatment-emergent anti-drug antibodies (ADAs) positive in a functional neutralizing antibody assay. No apparent impact of treatment-emergent ADAs on RICO activity or change from baseline in von Willebrand factor antigen concentration was found. Conclusions: The long-term safety profile of patients exposed to caplacizumab together with TPE+IST was similar to those who received IST+TPE only, with no observed increases in recurrence of aTTP. Repeat caplacizumab use was efficacious, with no evidence of safety concerns or boosting of ADA response. Funding: This research was funded by Ablynx, a Sanofi company. Figure 1 Figure 1. Disclosures Scully: Shire: Research Funding; Novartis: Research Funding, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octopharma: Speakers Bureau. de la Rubia: Ablynx/Sanofi: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Bristol Myers Squibb,: Honoraria, Speakers Bureau; Celgene, Takeda, Janssen, Sanofi: Honoraria; Celgene: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations; GSK: Consultancy. Pavenski: Alexion: Honoraria, Research Funding; Bioverativ: Research Funding; Ablynx: Honoraria, Research Funding; Octapharma: Research Funding; Shire: Honoraria. Metjian: Momenta/Johnson & Johnson, Sanofi Aventis, Takeda: Research Funding; Ablynx/Sanofi: Consultancy; Sanofi Aventis, Takeda: Other: Advisory. Knoebl: Ablynx/Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire/Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Peyvandi: Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Sobi: Consultancy, Honoraria. Cataland: Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding; Takeda: Consultancy; Sanofi Genzyme: Consultancy. Coppo: Alexion Pharmaceuticals, Sanofi Aventis, Octapharma AG: Consultancy, Other: Advisory; Alexion Pharmaceuticals, Sandoz, Sanofi Aventis, Takeda: Other: Speakers Bureau; Ablynx/Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kremer Hovinga Strebel: Ablynx/Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Speaker at symposia; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Other: Speaker at symposia; Roche: Other: Speaker at symposia; Siemens: Other: Speaker at symposia. Minkue Mi Edou: Sanofi: Current Employment, Other: May hold shares and/or stock options. de Passos Sousa: Sanofi: Current Employment, Other: May hold shares and/or stock options. Callewaert: Sanofi: Current Employment, Other: May hold shares and/or stock options. Gunawardena: Sanofi: Current Employment, Other: May hold shares and/or stock options. Lin: Sanofi: Current Employment, Other: May hold shares and/or stock options.

Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.

For longitudinal studies with multivariate observations, we propose statistical methods to identify clusters of archetypal subjects by using techniques from functional data analysis and to relate longitudinal patterns to outcomes. We demonstrate how this approach can be applied to examine associations between multiple time-varying exposures and subsequent health outcomes, where the former are recorded sparsely and irregularly in time, with emphasis on the utility of multiple longitudinal observations in the framework of dimension reduction techniques. In applications to children's growth data, we investigate archetypes of infant growth patterns and identify subgroups that are related to cognitive development in childhood. Specifically, "Stunting" and "Faltering" time-dynamic patterns of head circumference, body length and weight in the first 12 months are associated with lower levels of long-term cognitive development in comparison to "Generally Large" and "Catch-up" growth. Our findings provide evidence for the statistical association between multivariate growth patterns in infancy and long-term cognitive development.

Background: Novel and more effective therapies for multiple myeloma (MM) have led to increasing overall survival, but most patients (pts) will eventually relapse or become refractory (RR). The proteasome inhibitor (PI) bortezomib (V), the anti-CD38 antibody daratumumab (D), and dexamethasone (d) are key agents for combination therapy in first-line and RR settings. Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis in BCL-2-dependent MM cells in vitro. Encouraging clinical efficacy has been observed with Ven monotherapy in t(11;14) pts, and with VenV in pts irrespective of disease genetic background. In view of MM intraclonal heterogeneity, the addition of D to Ven +/- PI is postulated to further enhance antitumor activity of Ven-based regimens in RRMM. Methods: M15-654 (NCT03314181) is an ongoing Phase 1/2, nonrandomized, multicenter study of combination therapy consisting of VenDd +/- V in pts with RRMM. The primary objective is to evaluate the safety, tolerability, and preliminary efficacy of VenDd +/- V. In Part 1, VenDd was evaluated in t(11;14) MM pts who received ≥1 prior line of therapy that included a PI and an immunomodulatory drug (IMiD). In Part 2, VenDVd was evaluated in MM pts irrespective of t(11;14) status who were non-refractory to PIs and received 1 - 3 prior lines of therapy. Each regimen was evaluated in a dose escalation and expansion phase. In each part, Ven dose escalation was initiated at 400 mg daily (QD) and escalated to 800 mg QD if acceptable safety and tolerability were observed. Escalation cohorts had ≥3 pts, and escalation decisions were based on a Bayesian optimal interval design and the number of pts with a dose limiting toxicity (DLT). In Part 1, cycles (C) were 28-day: Ven QD + D 16 mg/kg intravenous (IV) (C1, 2: Days 1, 8, 15, 22; C3 - 6: Days 1, 15; C7+: Day 1) + d 40 mg total weekly. In Part 2, C1 - 8 were 21-day, C9+ were 28-day: Ven QD + D 16 mg/kg IV (C1 - 3: Days 1, 8, 15; C4+: Day 1) + V 1.3 mg/m2 subcutaneous (C1 - 8, Days 1, 4, 8, 11) + d 20 mg (C1 - 3: Days 1, 2, 4, 5, 8, 9, 11, 12, 15; C4 - 8, Days 1, 2, 4, 5, 8, 9, 11, 12) and 40 mg weekly for C9+. Results: As of 13 May 2019, 48 pts were enrolled. Of 24 t(11;14) pts treated in Part 1 with VenDd, median age was 63 (range, 51 - 76), median prior lines of therapy was 2.5 (range, 1 - 8), 14 (58%) had ISS II/III disease, and 24 (100%) received both prior PI and IMiD (46% refractory to PI, 71% refractory to IMiD, 42% double refractory). Of 24 pts treated in Part 2 with VenDVd, median age was 64 (range, 41 - 80), median prior lines of therapy was 1 (range, 1 - 3), 14 (58%) had ISS II/III disease, and 6 (25%) were t(11;14). Twenty-two (92%) pts received prior PI, 17 (71%) received prior IMiD (33% refractory), and 15 (63%) received prior PI + IMiD. The most common adverse events (AEs; VenDd/VenDVd) were fatigue (54%/21%), diarrhea (50%/42%), nausea (33%/38%), insomnia (29%/42%), cough (21%/8%), headache (21%/4%), upper respiratory tract infection (21%/17%), constipation (8%/33%), infusion related reaction (8%/33%), peripheral neuropathy (4%/25%), and dyspepsia (4%/21%). Grade 3/4 AEs were seen in 63%/54% of pts. The most common Grade 3/4 AEs in pts receiving VenDd were neutropenia (13%), fatigue, hyperglycemia, and hypertension (8% each); in pts receiving VenDVd, the most common were insomnia (17%), diarrhea, and thrombocytopenia (8% each). There were 6 pts with infection-related Grade 3/4 AEs (3 VenDd, 3 VenDVd). No AEs of tumor lysis syndrome were observed. Eleven pts had a serious AE (5 VenDd, 6 VenDVd), the most common being pyrexia in 3 pts. One pt treated with VenDd had a DLT of febrile neutropenia, and 1 pt treated with VenDVd died due to progressive disease. No infection-related deaths were seen. Pharmacokinetic analyses demonstrated that addition of D and V did not impact Ven exposure. Median time on study is 3.6 months (m; 8.1 m escalation, 2.8 m expansion) in the VenDd arm and 3.1 m (5.8 m escalation, 2.4 m expansion) in the VenDVd arm. The objective response rate (ORR) was 92% and 88% in pts receiving VenDd and VenDVd, respectively (Table). Conclusions: This first analysis of pts treated with VenDd +/- V demonstrate a tolerable safety profile with encouraging efficacy, notably among t(11;14) pts treated with VenDd who had an ORR of 92%. No new safety signals were observed. Although the study is currently on partial clinical hold, enrolled pts continue to be followed. Analysis will be updated at presentation. Disclosures Bahlis: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Baz:Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Merck: Research Funding; Sanofi: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: investigator on studies, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Quach:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Ho:Celgene: Membership on an entity's Board of Directors or advisory committees. Vangsted:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Jansen: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Gibbs:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Salem:AbbVie: Employment, Other: Stock/stock options. Ross:AbbVie: Employment, Other: Stock/stock options. Pesko:AbbVie: Employment, Other: Stock/stock options. Westrup:AbbVie: Employment, Other: Stock/stock options. Vue:AbbVie: Employment, Other: Stock/stock options. Maciag:AbbVie: Employment, Other: Stock/stock options. Bueno:AbbVie: Employment, Other: Stock/stock options. Kaufman:Takeda: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Winship Cancer Institute of Emory University: Employment; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy. OffLabel Disclosure: Venetoclax is a BCL-2 inhibitor that is FDA-approved in some indications. This presentation will focus on venetoclax for treatment of multiple myeloma, which is not an approved indication.

As emergency physicians with a subspecialty in aviation medicine, we agree with Dr. Rieb’s response[1][1] to an analysis article by Kodama and colleagues[2][2] that having naloxone on board is a necessary tool to treat the increasingly common medical emergency of opioid intoxication. Some airlines

Diffusion over a network refers to the phenomenon of a change of state of a cross-sectional unit in one period leading to a change of state of its neighbors in the network in the next period. One may estimate or test for diffusion by estimating a cross-sectionally aggregated correlation between neighbors over time from data. However, the estimated diffusion can be misleading if the diffusion is confounded by omitted covariates. This paper focuses on the measure of diffusion proposed by He and Song (2022, Preprint, arXiv:1812.04195v4 [stat.ME]), provides a method of decomposition analysis to measure the role of the covariates on the estimated diffusion, and develops an asymptotic inference procedure for the decomposition analysis in such a situation. This paper also presents results from a Monte Carlo study on the small sample performance of the inference procedure.

Abstract Objective To assess the long-term cost effectiveness of 1 year's treatment with clopidogrel on top of standard therapy (including aspirin; ASA) compared with standard therapy alone, in patients diagnosed with non-ST-segment-elevation acute coronary syndromes (ACS) in the UK. Design Cost utility analysis using a Markov model, incorporating clinical data from CURE (a multicentre randomised controlled trial, involving 12,562 patients) and data from UK observational studies. Setting Health economic evaluation carried out from the perspective of the UK NHS. Patients A representative cohort of 1000 UK patients aged 66 years, diagnosed with non-ST-segment-elevation ACS. Interventions Either a combination of 75 mg/day clopidogrel (300 mg loading dose, within 24 h prior to hospital admission) and standard therapy (including ASA, 75–325 mg/day) for 1 year followed by standard therapy alone for their remaining lifetime, or standard therapy alone (including ASA, 75–325 mg/day) for life. Main outcome measures Incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. Results In the base case, the incremental cost effectiveness of the clopidogrel combination vs standard therapy alone is estimated as £6991 per life-year gained and £7365 per QALY gained. The probability that clopidogrel remains cost effective within the generally accepted £30,000 per QALY threshold is more than 80%. The confidence interval around the relative risk for vascular death was identified as the main parameter affecting the estimated cost effectiveness. Conclusions One year's treatment with clopidogrel is a cost effective intervention compared with standard therapy that should be considered as a routine treatment for patients with non-ST-segment-elevation ACS.