BACKGROUND AND AIMS: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. METHODS: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohn's disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n=18) or resistance (n=5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. RESULTS: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. CONCLUSIONS: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.
Previously, this study group found that female childhood cancer survivors could be at risk of early cessation of fertility. The aim of the present study was to evaluate reproductive function in the same group of survivors 10 years after the initial study. Of the original cohort of 100, 71 were re-examined. Thirty-six survivors reported regular menstrual cycles. When they were compared with 210 controls, they differed significantly in antral follicle count (AFC) (median 15 versus 18, P=0.047) but not in anti-Müllerian hormone (AMH) (median 13.0 versus 17.8 pmol/l). Survivors cured with minimal gonadotoxic treatment had significantly higher AMH and AFC compared with survivors cured with either potentially gonadotoxic treatment or treatment including alkylating chemotherapy and ovarian irradiation (20.0, 5.8 and
This project studies the effect of group-based Acceptance and Commitment Therapy (ACT) following Attention Bias Modification (ABM) on residual symptoms in recurrent depression. ACT is a cognitive-behavioral intervention combining acceptance and mindfulness processes with commitment and behavior-change processes. ACT enjoys modest empirical support in treating depression and has also shown promising results in secondary prevention of depression. The experimental cognitive bias modification (ABM) procedure has been shown to reduce surrogate markers of depression vulnerability in patients in remission from depression. The aim of the current project is to investigate if the effect of group-based ACT on reducing residual depressive symptoms can be enhanced by preceding it with ABM. Also, assessment of the relationship between conceptually relevant therapeutic processes and outcome will be investigated.
An invitation to participate in this project was extended to 120 individuals within a larger sample who had just completed a separate randomized, multisite, clinical trial (referred to hereafter as Phase 1) in which they received either ABM (n = 60) or a control condition without bias modification (n = 60). This larger Phase-1 sample consisted of 220 persons with a history of at least two episodes of major depression who were currently in remission or not fulfilling the criteria of major depression. After its inclusion, Phase-1 participants from the Sørlandet site (n = 120) were also recruited for this study in which they received an 8-week group-based ACT intervention. Measures will be taken immediately after Phase 1, 1 month, 2 months, 6 months, and 1 year after the conclusion of Phase 1.
This study sequentially combines acceptable, nondrug interventions from neuropsychology and cognitive-behavioral psychology in treating residual symptoms in depression. The results will provide information about the effectiveness of treatment and on mechanisms and processes of change that may be valuable in understanding and further developing ABM and ACT, combined and alone.
ClinicalTrials.gov, Identifier: NCT02648165 . Registered on 6 January 2016.
To examine the frequency of 6 definitions for remission and 4 definitions for low disease activity (LDA) after starting a disease-modifying antirheumatic drug (DMARD) in patients with rheumatoid arthritis (RA) in clinical practice, and to study whether predictors for achieving remission after 6 months are similar for these definitions.
Remission and LDA were calculated according to the 28-joint Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), the Routine Assessment of Patient Index Data (RAPID3), and both the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission definitions 3 and 6 months after 4992 DMARD prescriptions for patients enrolled in the NOR-DMARD, a 5-center Norwegian register. Prediction of remission after 6 months was also studied.
After 3 months, remission rates varied between definitions from 8.7% to 22.5% and for LDA from 35.5% to 42.7%, and increased slightly until 6 months of followup. DAS28 and RAPID3 gave the highest and ACR/EULAR, SDAI, and CDAI the lowest proportions for remission. Positive predictors for remission after 6 months were similar across the definitions and included lower age, male sex, short disease duration, high level of education, current nonsmoking, nonerosive disease, treatment with a biological DMARD, being DMARD-naive, good physical function, little fatigue, and LDA.
In daily clinical practice, the DAS28 and RAPID3 definitions identified remission about twice as often as the ACR/EULAR Boolean, SDAI, and CDAI. Predictors of remission were similar across remission definitions. These findings provide additional evidence to follow treatment recommendations and treat RA early with a DMARD.
Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial. The Danish Society of Hematology Study Group on AML, Denmark.
A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.
Effects were studied of a complex treatment combined with enterosorption on the clinical course of tuberculosis of the respiratory organs in children. The results obtained showed that the use of enterosorbents "Carbolong" or "Carbosfer" against the background of the chemotherapy adopted leads to a significant shortening of periods of detoxication, which fact is manifested by a quicker and more marked positive dynamics of intoxicative symptomatology by comparison with those patients having received a conventional course of chemotherapy only. In a comparative evaluation of the natural enterosorbent Carbolong versus synthetic enterosorbent Carbosfer they were shown to be of similar therapeutic activity.
In a ten-year retrospective singlecenter study of a nonselected patient population, we describe our experience with an unchanged chemotherapy regimen for 264 patients with acute myeloid leukemia (AML) and 51 patients with acute lymphoblastic leukemia (ALL). In the AML group, 85 patients could not receive specific antileukemic treatment because of uncontrollable bleeding, infection or organ failure, but 179 were fit for remission-induction therapy with cytarabine and daunorubicin, resulting in complete remission in 79 patients. During treatment, 54 patients died of resistant disease or complications. The median duration of survival of the patients in complete remission was 18-24 months (n = 79) compared with 1-2 months for patients in partial or no remission (n = 100). As maintenance chemotherapy, thioguanine, cytarabine and daunorubicin were given for one year. In the ALL group 50 of 51 patients received remission-induction therapy with vincristine, prednisone and Adriablastin, resulting in complete remission in 39 of the patients. The median duration of survival of the patients in complete remission was nine months (n = 39) compared with 2-3 months for patients not in remission (n = 12). Central nervous system prophylaxis with intraspinal methotrexate and cranial irradiation was given, followed by methotrexate and Purinetol for three years as maintenance chemotherapy. The remission rate for AML and adult ALL was 44% and 78%, respectively. The major Cause of death after first complete remission was leukemic relapse in boths groups, with a median survival time after relapse of 3-4 months for 48 AML and six months for 30 ALL patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome.
To the authors' knowledge, the natural history of myelosuppression and infectious complications associated with the use of standard cytarabine (ARA-C) plus daunorubicin ("7 + 3") remission-induction therapy for adult acute myeloid leukemia (AML) and high dose ARA-C (HDARA-C) consolidation has not been described completely.
A retrospective study of untreated adult AML patients receiving standard 7 + 3 induction followed by "5 + 2" and HDARA-C consolidation was undertaken to describe the relationship of the myelosuppression profiles, blood product use, and infectious morbidity, and to correlate this finding with the outcome of antileukemic therapy. Multivariate techniques were used to evaluate variables of prognostic importance.
Fifty-nine percent of the patients achieved remission after a median of 35 days; almost half (48%) of these patients required more than one 7 + 3 induction course. For one, two, and three induction courses, the mean number of days the patients experienced severe neutropenia (