Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation

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Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoid arthritis patients

BACKGROUND: Neuropsychiatric adverse drug reactions (NPADRs) are not commonly associated with low dose methotrexate (LDMTX) in patients with rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: In this case series assessment, we described the nature and frequency of NPADRs with LDMTX in the Dutch DREAM-RA registry, including causality of NPADRs, the impact on further LDMTX treatment and the impact on patient reported Health Related Quality of Life (HRQoL). RESULTS: A total of 71 NPADRs (frequency 6.8%) associated with LDMTX were captured in the DREAM-RA registry. NPADRs were registered for 62 (5.9%) out of 1048 patients with 10.9 NPADRs per 1000 patient years. Headache, dizziness and depression were most frequently reported. The causality was considered probable for 67 NPADRs (94.4%) and definite for 1 NPADR (1.4%). NPADRs led to LDMTX withdrawal in 34 cases (47.9%) and was not restarted in 16 cases (47.1%). Median mental HRQoL was significantly decreased around the occurrence of the NPADR and remained significantly lower after the event. Median physical HRQoL was not significantly affected. CONCLUSIONS: Knowledge on the nature, frequency and impact of the demonstrated NPADRs during LDMTX therapy will enhance attention toward these potential ADRs allowing better risk assessment and communication to patients

Maximum principle and mutation thresholds for four-letter sequence evolution

A four-state mutation-selection model for the evolution of populations of DNA-sequences is investigated with particular interest in the phenomenon of error thresholds. The mutation model considered is the Kimura 3ST mutation scheme, fitness functions, which determine the selection process, come from the permutation-invariant class. Error thresholds can be found for various fitness functions, the phase diagrams are more interesting than for equivalent two-state models. Results for (small) finite sequence lengths are compared with those for infinite sequence length, obtained via a maximum principle that is equivalent to the principle of minimal free energy in physics.Comment: 25 pages, 16 figure

A revised day +7 predictive score for transplant-related mortality: serum cholinesterase, total protein, blood urea nitrogen, γ glutamyl transferase, donor type and cell dose

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Automating Change of Representation for Proofs in Discrete Mathematics (Extended Version)

Representation determines how we can reason about a specific problem. Sometimes one representation helps us find a proof more easily than others. Most current automated reasoning tools focus on reasoning within one representation. There is, therefore, a need for the development of better tools to mechanise and automate formal and logically sound changes of representation. In this paper we look at examples of representational transformations in discrete mathematics, and show how we have used Isabelle's Transfer tool to automate the use of these transformations in proofs. We give a brief overview of a general theory of transformations that we consider appropriate for thinking about the matter, and we explain how it relates to the Transfer package. We show our progress towards developing a general tactic that incorporates the automatic search for representation within the proving process

Invasive fungal infections in patients with acute myeloid leucemia and in those submitted to allogeneic hemopoieticstem cell transplant: who is at highest risk ?

Invasive fungal infections (IFIs) are a growing cause of morbidity and mortality in patients with acute myeloid leukemia (AMLs) and in recipients of allogeneic hemopoietic stem cell transplantation (allo-HSCTs) (1–6). It is widely debated if either allo-HSCTs or AMLs are to be considered at higher risk, but no data comparing the two categories of patients have been reported in literature so far. This cohort study has been conducted from January 1999 to December 2003 in hematology wards located throughout Italy. The study was aimed at evaluating the incidence and mortality for IFIs in adult AMLs and in patients submitted to all types of allo-HSCT procedures; a comparison between the two categories of patients was carried out

Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT

Gastrointestinal adverse drug reaction profile of etanercept:Real world data from patients and healthcare professionals

Objective. We aimed to describe the nature and frequency of gastrointestinal adverse drug reactions (GI-ADRs) of etanercept (ETN) using patient-reported and healthcare professional (HCP)-registered data and compared this frequency with the GI-ADR frequency of the widely used tumor necrosis factor-α inhibitor adalimumab (ADA). Methods. Reported GI-ADRs of ETN for rheumatic diseases were collected from the Dutch Biologic Monitor and DREAM registries. We described the clinical course of GI-ADRs and compared the frequency with ADA in both data sources using Fisher exact test. Results. Out of 416 patients using ETN for inflammatory rheumatic diseases in the Dutch Biologic Monitor, 25 (6%) patients reported 36 GI-ADRs. In the DREAM registries 11 GI-ADRs were registered for 9 patients (2.3%), out of 399 patients using ETN, with an incidence of 7.1 per 1000 patient-years. Most GI-ADRs consisted of diarrhea, nausea, and abdominal pain. GI-ADRs led to ETN discontinuation in 1 patient (4%) and dose adjustment in 4 (16%) in the Dutch Biologic Monitor. Eight GI-ADRs (73%) led to ETN discontinuation in the DREAM registries. The frequency of GI-ADRs of ETN did not significantly differ from GI-ADRs of ADA in both data sources (Dutch Biologic Monitor: ETN 8.7% vs ADA 5.3%, P = 0.07; DREAM: ETN 2.8% vs ADA 4.7%, P = 0.16). Conclusion. Most GI-ADRs associated with ETN concerned gastrointestinal symptoms. These ADRs may lead to dose adjustment or ETN discontinuation. The frequency of ETN-associated GI-ADRs was comparable to the frequency of ADA-associated GI-ADRs. Knowledge about these previously unknown ADRs can facilitate early recognition and improve patient communication