The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher ...risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed with a median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality.
BackgroundClusters of COPD patients have been reported in order to individualize the treatment program. Neither co-morbidity clusters, nor integrated respiratory physiomics clusters contributed to a ...better prediction of outcomes. Based on a thoroughly assessed set of pulmonary and extra-pulmonary traits at the start of a pulmonary rehabilitation (PR) program, we recently described seven clusters of COPD patients. The aims of this study are to confirm multidimensional differential response and to assess the potential of pulmonary and extra-pulmonary traits-based clusters to predict this multidimensional response to PR pulmonary in COPD patients.MethodsOutcomes of a 40-session PR program for COPD patients, referred by a chest physician, were evaluated based on the minimal clinically important difference (MCID) for 6-minute walk distance (6MWD), cycle endurance time, Canadian Occupational Performance Measure performance and satisfaction scores, Hospital Anxiety and Depression Scale anxiety and depression scores, MRC dyspnea grade and St George's Respiratory Questionnaire. The aforementioned response indicators were used to calculate the overall multidimensional response and patients were grouped in very good, good, moderate and poor responders. In the same way, responses to pulmonary rehabilitation were compared based on seven previously identified pulmonary and extra-pulmonary traits-based clusters.ResultsOf the whole sample, drop out was 19% and 419 patients (55.4% males, age: 64.3 ± 8.8, FEV1% of predicted: 48.9 ± 20) completed the pulmonary rehabilitation program. Very good responders had significantly worse baseline characteristics with a higher burden of disease, a higher proportion of rollator-users, higher body mass index (BMI), more limitations of activities in daily life, emotional dysfunction, higher symptoms of dyspnea and worse quality of life. Of the seven pre-identified clusters, 'the overall best functioning cluster' and 'the low disease burden cluster' both including the best 6MWD, the lowest dyspnea score and the overall best health status, demonstrated attenuated outcomes, while in 'the cluster of disabled patients', 76% of the patients improved health status with at least 2 times MCID. This 'cluster of disabled patients' as well as 'the multimorbid cluster', 'the emotionally dysfunctioning cluster', 'the overall worst-functioning cluster' and 'the physically dysfunctioning cluster' all demonstrated improvements in performance and satisfaction for occupational activities (more than 65% of patients improved with > 1MCID), emotional functioning (more than 50% of patients improved with > 1 MCID) and overall health status (more than 58%).ConclusionThe current study confirms the differential response to pulmonary rehabilitation based on multidimensional response profiling. Cluster analysis of baseline traits illustrates that non-linear, clinically important differences can be achieved in the most functionally and emotionally impaired clusters and that 'the overall best functional cluster' as well as 'the low disease burden cluster' had an attenuated outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic prurigo (CPG) is a highly burdensome pruritic disease characterized by chronic itch, a prolonged scratching behavior and the development of localized or generalized hyperkeratotic pruriginous ...lesions. Neuronal sensitization and the development of an itch-scratch cycle contribute to the augmentation of pruritus and the chronicity of the disease. We provide here the first international guideline for a rational diagnostic and therapeutic approach for CPG. Recommendations are based on available evidence and expert opinion. The diagnosis of CPG is made clinically. A detailed medical history together with laboratory and radiological examinations are advised in order to determine the severity of CPG, identify the underlying origin of the itch and assist in the elaboration of a treatment plan. Therapeutically, it is advised to adopt a multimodal approach, including general strategies to control itch, treatment of the underlying pruritic conditions, and of the pruriginous lesions. Topical (corticosteroids, calcineurin inhibitors, capsaicin) and systemic antipruritic agents (eg, gabapentinoids, immunosuppressants, and opioid modulators) as well as physical treatment modalities (phototherapy, cryotherapy) should be employed in a step-wise approach. Psychosomatic or psychological interventions may be recommended in CPG patients with signs of psychiatric/psychological comorbidities.
The Third International Consensus Conference for Advanced Breast Cancer ABC3 on the diagnosis and treatment of advanced breast cancer was held in Lisbon from 5 to 7 November 2015. This year the focus ...was the treatment of metastatic breast cancer (stage IV) - including the patient perspectives. Important topics were questions relating to quality of life, the care for long-term survivors as well as the management of disease-related symptoms and treatment-based side effects. The use of standardised tools to assess individual treatment success and the benefits of new substances were important points for discussion. The diagnosis and treatment of inoperable locally advanced breast cancer were discussed two years ago during the ABC2 consensus 1. A working group of German breast cancer experts commented on the results of the ABC panellists, paying particular attention to the German guidelines (AGO, S3, DGHO) on the diagnosis and treatment of breast cancer 2, 3, 4, 5 in Germany.
Little is known about determinants of second-generation antipsychotic dosages during initial hospitalization of first-episode psychosis. This study examined potential predictors of dosage of an ...atypical antipsychotic agent, risperidone, at hospital discharge after initial evaluation and treatment of first-episode nonaffective psychosis in 3 naturalistic, public-sector treatment settings.
The number of psychotropic agents prescribed and discharge antipsychotic dosage were abstracted from the medical record. Demographic and extensive clinical characteristics were assessed through a clinical research study conducted at the 3 sites. One-way analyses of variance, trend tests using specific linear combinations of estimates, and χ² tests assessed for associations between atypical antipsychotic dosage and 5 hypothesized predictors, as well as 12 exploratory variables.
Among 155 hospitalized first-episode patients, 121 (78.1%) were discharged on risperidone, and subsequent analyses focused on that subset. The mean risperidone dosage among those 121 patients was 4.26 mg; 31 received 1 to 2 mg, 45 received 3 to 4 mg, 37 received 5 to 6 mg, and 8 received more than 6 mg. Analyses suggested that older age at hospitalization, the number of psychotropic agents prescribed, excited symptoms, and premorbid social functioning may be predictors of the discharge dosage.
Although several factors emerged, in general, predictors of discharge dosages of second-generation agents, here exemplified by risperidone, in real-world practice settings remain to be clarified. Given the importance of antipsychotic initiation during first hospitalization, future research should test an even broader array of potential predictors.
Dipeptidyl nitrile inhibitors of Cathepsin L Asaad, Nabil; Bethel, Paul A.; Coulson, Michelle D. ...
Bioorganic & medicinal chemistry letters,
08/2009, Letnik:
19, Številka:
15
Journal Article
Recenzirano
A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand ...complex.
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