OBJECTIVE: In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping. METHODS: Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068). RESULTS: During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin. CONCLUSION: Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess. TRIAL REGISTRATION NUMBER: NCT01776424.

• MeSH
• Aspirin * administration & dosage   adverse effects   MeSH
• Fibrinolytic Agents administration & dosage   adverse effects   MeSH
• Myocardial Infarction * etiology   mortality   prevention & control   MeSH
• Ischemic Stroke * etiology   mortality   prevention & control   MeSH
• Drug Therapy, Combination methods   MeSH
• Coronary Disease * diagnosis   drug therapy   MeSH
• Humans MeSH
• Drug Monitoring methods   statistics & numerical data   MeSH
• Mortality MeSH
• Drug Substitution adverse effects   MeSH
• Withholding Treatment statistics & numerical data   MeSH
• Peripheral Arterial Disease * diagnosis   drug therapy   MeSH
• Rivaroxaban * administration & dosage   adverse effects   MeSH
• Aged MeSH
• Duration of Therapy MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Fusion Proteins, bcr-abl genetics   MeSH
• Time Factors MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy   genetics   pathology   MeSH
• Remission Induction MeSH
• Protein Kinase Inhibitors adverse effects   MeSH
• Clinical Trials as Topic methods   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local chemically induced   diagnosis   epidemiology   MeSH
• Withholding Treatment statistics & numerical data   MeSH
• Prognosis MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

OBJECTIVES: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. METHODS: We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. RESULTS: Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). CONCLUSION: Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.

• MeSH
• Antirheumatic Agents * classification   immunology   therapeutic use   MeSH
• Biological Products * classification   immunology   therapeutic use   MeSH
• Drug Interactions immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• International Cooperation MeSH
• Monitoring, Immunologic * methods   statistics & numerical data   MeSH
• Withholding Treatment statistics & numerical data   MeSH
• Patient Acuity MeSH
• Registries statistics & numerical data   MeSH
• Arthritis, Rheumatoid * diagnosis   drug therapy   epidemiology   immunology   MeSH
• Rheumatoid Factor blood   MeSH
• Duration of Therapy MeSH
• Patient Selection MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874.

• MeSH
• Time Factors MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy   pathology   MeSH
• Imatinib Mesylate therapeutic use   MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   pathology   MeSH
• Survival Rate MeSH
• Follow-Up Studies MeSH
• Withholding Treatment statistics & numerical data   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Euthanasia * ethics   statistics & numerical data   MeSH
• Intensive Care Units ethics   MeSH
• Critical Illness MeSH
• Quality of Life MeSH
• Humans MeSH
• Withholding Treatment ethics   statistics & numerical data   MeSH
• Critical Care * ethics   MeSH
• Terminal Care ethics   statistics & numerical data   MeSH
• Heart-Assist Devices ethics   MeSH
• Decision Making ethics   MeSH
• Professional-Family Relations ethics   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Euthanasia, Active MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Withholding Treatment * statistics & numerical data   MeSH
• Euthanasia, Passive MeSH
• Critical Care MeSH
• Check Tag
• Humans MeSH
• Publication type
• News MeSH

We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1, 31%), and frail (score ≥2, 30%). The 3-year overall survival was 84% in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P < .001) patients. The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness (HR, 1.23; P = .217), and 34.0% in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. These trials are registered at www.clinicaltrials.gov as #NCT01093136 (EMN01), #NCT01190787 (26866138MMY2069), and #NCT01346787 (IST-CAR-506).

• MeSH
• Geriatric Assessment * MeSH
• Clinical Trials as Topic MeSH
• Cohort Studies MeSH
• Frail Elderly * MeSH
• Humans MeSH
• Multiple Myeloma drug therapy   mortality   MeSH
• Withholding Treatment statistics & numerical data   MeSH
• Prognosis MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

Cíl Pacienti s nádorovým onemocněním jsou na konci života z důvodu přítomnosti závažných příznaků a specifického průběhu nemoci častěji než ostatní pacienti postaveni před rozhodnutí s možným nebo jistým dopadem na zkrácení délky života (end‑of‑life decisions, ELD). Tato studie porovnává incidenci ELD u pacientů s nádorovým onemocněním oproti pacientům s nemaligním onemocněním a popisuje trendy v incidenci ELD mezi lety 1998 a 2007. Pacienti a metody V r. 2007 byla ve Flandrech v Belgii provedena celonárodní studie úmrtních listů analogická předchozí studii z r. 1998. Lékařům, kteří vyplnili vybrané úmrtní listy (n = 6 927), byl rozeslán dotazník. Výsledky Míra návratnosti dotazníků činila 58,4 % a náhlá úmrtí byla vyloučena z hodnocení. Intenzifikovaná symptomatická léčba byla podána pacientům s nádorovým onemocněním častěji než ostatním pacientům (53,8 % vs. 31,7 %; p < 0,001) stejně jako eutanazie (6,8 % vs. 0,9 %; p < 0,001). V incidenci tzv. rozhodnutí neléčit a ukončení života bez výslovné žádosti pacienta nebyly mezi oběma skupinami zjištěny významné rozdíly. Ze skupiny pacientů považovaných za kompetentní k ELD se pacienti s nádorovým onemocněním účastnili rozhodovacího procesu méně často než pacienti s jinými terminálními stavy (69,7 % vs. 83,5 %, p = 0,001). Mezi lety 1998 a 2007 se incidence ELD zvýšila u pacientů s nádorovým onemocněním (o 6,7 %) a ještě výrazněji u pacientů s jinými terminálními stavy (o 14,9 %) z důvodu častější indikace intenzifikované symptomatické léčby. U pacientů s nádorovým onemocněním došlo ke značnému nárůstu případů eutanazie, a naopak k poklesu počtu případů ukončení života bez výslovné žádosti pacienta. Závěr Vyšší incidence ELD u pacientů s nádorovým onemocněním oproti pacientům s jinými terminálními stavy pravděpodobně souvisí s rozdíly v průběhu nemoci a přístupu k paliativní péči mezi oběma skupinami. V období mezi lety 1998 a 2007, kdy došlo k legalizaci eutanazie a posílení paliativní péče, se zvýšil celkový počet ELD zahrnujících zmírnění symptomů a eutanazii, a naopak klesl počet případů ukončení života bez výslovné žádosti pacienta.

• MeSH
• Child MeSH
• Adult MeSH
• Euthanasia statistics & numerical data   MeSH
• Incidence MeSH
• Practice Patterns, Physicians' statistics & numerical data   trends   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Neoplasms epidemiology   psychology   therapy   MeSH
• Withholding Treatment statistics & numerical data   MeSH
• Palliative Care * methods   trends   MeSH
• Terminal Care * methods   statistics & numerical data   MeSH
• Cause of Death MeSH
• Surveys and Questionnaires * MeSH
• Decision Making MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Suicide, Assisted * statistics & numerical data   trends   MeSH
• Death Certificates * MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Belgium MeSH

• Keywords
• auto-resuscitace, konstatování smrti,
• MeSH
• Cardiopulmonary Resuscitation methods   standards   MeSH
• Withholding Treatment standards   statistics & numerical data   MeSH
• Death MeSH

• MeSH
• Child MeSH
• Financing, Organized MeSH
• Adrenal Cortex Hormones administration & dosage   therapeutic use   MeSH
• Drug Therapy, Combination methods   statistics & numerical data   MeSH
• Humans MeSH
• Antibodies, Monoclonal administration & dosage   therapeutic use   MeSH
• Multicenter Studies as Topic MeSH
• Withholding Treatment statistics & numerical data   utilization   MeSH
• Postoperative Complications drug therapy   prevention & control   MeSH
• Growth drug effects   MeSH
• Tacrolimus administration & dosage   therapeutic use   MeSH
• Kidney Transplantation statistics & numerical data   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Meeting Abstract MeSH