BACKGROUND: Recently, new advances were made regarding the depletion of CD45RA+ naïve T cells from haploidentical grafts as they are suspected to be the most alloreactive. METHODS: Within this project we investigated CD45RA-depletion from G-CSF mobilized PBSC by two different purification strategies according to GMP, specifically direct depletion of CD45RA+ cells (one-step approach), or CD34-positive selection followed by CD45RA-depletion (two-step approach). RESULTS: With log -3.9 and - 3.8 the depletion quality of CD45RA+ T cells was equally for both approaches together with a close to complete CD19+ B cell depletion. However, due to a high expression of CD45RA the majority of NK cells were lost within both CD45RA depletion strategies. Stem cell recovery after one-step CD45RA-depletion was at median 52.0% (range: 49.7-67.2%), which was comparable to previously published recovery data received from direct CD34 positive selection. Memory T cell recovery including CD4+ and CD8+ memory T cell subsets was statistically not differing between both purification approaches. The recovery of CD4+ and CD8+ T cells was as well similar, but overall a higher amount of cytotoxic than T-helper cells were lost as indicated by an increase of the CD4/CD8 ratio. CONCLUSIONS: CD45RA-depletion from G-CSF mobilized PBSC is feasible as one- and two-step approach and results in sufficient reduction of CD45RA+ T cells as well as B cells, but also to a co-depletion of NK cells. However, by gaining two independent cell products, the two-step approach enables the highest clinical flexibility in regard to individual graft composition with precise dosage of stem cells and T cells.
Lymphocyte Depletion/methods , T-Lymphocyte Subsets/immunology , Feasibility Studies , Flow Cytometry , Granulocyte Colony-Stimulating Factor/immunology , Granulocyte Colony-Stimulating Factor/metabolism , Humans , Leukocyte Common Antigens/metabolism , Lymphocyte Depletion/instrumentation , T-Lymphocyte Subsets/metabolism
INTRODUCTION: Polypharmacy increases the risk of side effects and interactions. We quantified the prevalence of major polypharmacy (MPP) in a Danish county with 236,000 inhabitants, invited general practitioners (GPs) to participate in a quality improvement project and discussed the medication of 10-20 MPP patients selected by the participating GPs. MATERIAL AND METHODS: This was a prospective registry study of all prescriptions of subsidized drugs in the third quarter of 2005 for all inhabitants living in Roskilde County, Denmark. An audit was performed of the prescriptions of 220 MPP patients selected by the GPs based on a list of each MPP patient's medications. RESULTS: MPP patients constituted 2.1% of the county's population. GPs demonstrated a strong interest in auditing prescriptions. A large share of the patients selected by the GPs was treated with drugs which were no longer indicated, or with drugs with a doubtful indication. CONCLUSIONS: MPP compromises the GP's ability to manage medication of individual patients. Systematic audit of the total medication of patients should be introduced.
General Practice/statistics & numerical data , Polypharmacy , Databases, Factual , Denmark , Female , Humans , Male , Medical Audit , Middle Aged , Practice Patterns, Physicians'/statistics & numerical data , Prevalence , Prospective Studies , Registries
INTRODUCTION: General practice is responsible for 75% of drug costs in the Danish primary health care sector, but little information is available on how drugs are prescribed or on the division of labour between GPs and receptionists. MATERIALS AND METHODS: Prospective questionnaire study by patient, GP working single-handedly and/or receptionist of contacts leading to prescribing. RESULTS: 14 practices with 25,111 enrolled citizens completed the study. During the study period GPs/receptionists prescribed drugs to 1,391 patients, 493 (35%) of which were by GPs and 898 (65%) by receptionists on behalf of the GP. 62% of the GPs' and 93% of the receptionists' prescriptions were repeat prescriptions. Plans for duration of treatment in patient records were rare, and there were significant disagreements between patients and GPs about whether follow-up and duration of treatment was planned. Two thirds of patients wanted a less expensive drug, but the price was only discussed in 10% of prescriptions. DISCUSSION: Receptionists are responsible for a large share of repeat prescriptions and, surprisingly, for new prescriptions as well. Receptionists cannot decide to stop prescribing to a patient or find the least expensive analogue drug. Therefore, the GP should participate in decision-making about prescriptions.
Drug Prescriptions , Practice Patterns, Physicians' , Private Practice , Decision Making , Denmark , Drug Costs , Drug Prescriptions/economics , Drug Prescriptions/statistics & numerical data , Humans , Medical Receptionists , Patient Satisfaction , Physicians, Family , Practice Patterns, Physicians'/economics , Practice Patterns, Physicians'/statistics & numerical data , Private Practice/economics , Private Practice/statistics & numerical data , Prospective Studies , Surveys and Questionnaires
We investigated the effects of a multi-dimensional intervention on practice prescription patterns in five drug groups. The number of prescribed defined daily doses (DDDs) increased after the intervention, while potential savings/DDD decreased. The county's average cost/DDD fell to a level below the national average. It is possible to change general practitioners' prescription patterns without interfering with their clinical freedom or patients' access to treatment.
Drug Prescriptions , Drug Utilization , Practice Patterns, Physicians' , Denmark , Drug Costs , Family Practice , Feedback , Humans , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/economics , Practice Guidelines as Topic
PURPOSE: To investigate whether and how a multi-dimensional intervention including clinical guidelines on the choice of medical treatment in the primary and the secondary health care sector, and individual feedback to general practices about their own and other practices' prescription patterns in five Anatomical Therapeutic Chemical classification system (ATC)-groups was followed by changes in the practices' prescription pattern. METHODS: Prospective historical registry study and a questionnaire study of GPs' self-reported use of guidelines and feedback. RESULTS: In every ATC-group the number of prescribed defined daily doses (DDDs) kept growing after the intervention, while potential savings by DDD decreased. Individual practices' changes in the prescription pattern differed by ATC-group and practices with high potential savings/DDD before the intervention showed the greatest relative reduction in potential savings/DDD. The county's average cost/DDD for the five ATC-groups declined from above the Danish average before the intervention to a level below the average cost/DDD after the intervention. In the questionnaire study (response rate: 79%), 69% of respondents had read the guidelines and 78% reported that the feedback influenced their prescription of drugs. CONCLUSIONS: The observed changes in drug costs and potential savings were not due to volume effects but a combination of price effects, including generic substitution and choice of less expensive analogues, demonstrating that it is possible to change GPs' prescription patterns without interfering with patients' access to treatment or with GPs' clinical freedom.'
Drug Utilization , Feedback , Practice Guidelines as Topic , Practice Patterns, Physicians' , Drug Costs , Humans
