Preventing hospital admissions by reviewing medication (PHARM) in primary care: design of the cluster randomised, controlled, multi-centre PHARM-study.

BACKGROUND: Medication can be effective but can also be harmful and even cause hospital admissions. Medication review or pharmacotherapy review has often been proposed as a solution to prevent these admissions and to improve the effectiveness and safety of pharmacotherapy. However, most published randomised controlled trials on pharmacotherapy reviews showed no or little effect on morbidity and mortality. Therefore we designed the PHARM (Preventing Hospital Admissions by Reviewing Medication)-study with the objective to study the effect of the total pharmaceutical care process on medication related hospital admissions and on adverse drug events, survival and quality of life. METHODS/DESIGN: The PHARM-study is designed as a cluster randomised, controlled, multi-centre study in an integrated primary care setting. Patients with a high risk of a medication related hospital admission are included in the study with randomisation at GP (general practitioner) level. We aim to include 14200 patients, 7100 in each arm, from at least 142 pharmacy practices.The intervention consists of a patient-centred, structured, pharmaceutical care process. This process consists of several steps, is continuous and occurs over multiple encounters of patients and clinicians. The steps of this pharmaceutical care process are a pharmaceutical anamnesis, a review of the patient's pharmacotherapy, the formulation and execution of a pharmaceutical care plan combined with the monitoring and follow up evaluation of the care plan and pharmacotherapy. The patient's own pharmacist and GP carry out the intervention. The control group receives usual care.The primary outcome of the study is the frequency of hospital admissions related to medication within the study period of 12 months of each patient. The secondary outcomes are survival, quality of life, adverse drug events and severe adverse drug events. The outcomes will be analysed by using mixed-effects Cox models. DISCUSSION: The PHARM-study is one of the largest controlled trials to study the effectiveness of the total pharmaceutical care process. The study should therefore provide evidence as to whether such a pharmaceutical care process should be implemented in the primary care setting. TRIAL NUMBER: NTR 2647.

Successful treatment of life-threatening postpartum hemorrhage with recombinant activated factor VII.

BACKGROUND: Postpartum hemorrhage is one of the most common causes of maternal mortality and morbidity worldwide. The aims of treatment are to maintain the circulation and to stop the bleeding. The latter is achieved by either medical or surgical management. In intractable bleeding, emergency hysterectomy is usually required. CASE: A 30-year-old nullipara presented with major postpartum hemorrhage due to uterine atony and vaginal lacerations. The patient developed hemorrhagic shock, resulting in prolonged prothrombin time, prolonged activated partial thromboplastin time, and low levels of factor VIII and fibrinogen. Treatments with uterotonic drugs, suturing, ligation of internal iliac arteries, subtotal hysterectomy, packing of the pelvis, and blood transfusion failed to control diffuse pelvic and vaginal bleeding. Recombinant activated factor VIIa (60-microg/kg intravenous bolus injection) was given as a final attempt to control the bleeding. The bleeding was successfully controlled within 10 minutes after administration. No side effects were noted. CONCLUSION: Recombinant factor VIIa may be an alternative hemostatic agent in a patient with life-threatening postpartum hemorrhage unresponsive to conventional therapy.

Granulocyte colony-stimulating factor mobilized whole blood containing over 0.3 x 106/kg CD34+ cells is a sufficient graft in autologous transplantation for relapsed non-Hodgkin's lymphoma.

The feasibility of unprocessed, granulocyte colony-stimulating factor (G-CSF)-mobilized whole blood (WB) as an alternative stem cell source for autologous stem cell transplantation was studied. Forty-seven relapsed non-Hodgkin's lymphoma (NHL) patients entered the study. After two or three ifosfamide, methotrexate and etoposide (IMVP) courses, 1 l of G-CSF-mobilized WB was collected and stored refrigerated for 72 h. Meanwhile, BAM conditioning was given: BCNU (carmustine) 300 mg/m(2), high-dose cytarabine 6000 mg/m(2) and melphalan 140 mg/m(2). Toxicity, haematological recovery and survival were assessed and compared with peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) reference groups. High-dose G-CSF (2 x 12 microg/kg/d) gave the best mobilization results. Haematological recovery was related to the WB CD34+ content. A CD34+ threshold of >or= 0.3 10(6)/kg, obtained in 90% of patients using high-dose G-CSF, correlated with adequate recovery: absolute neutrophil count (ANC) > 0.5 x 10(9)/l: median 12 d (range 9-19). Platelet recovery > 20 and > 50 x 10(9)/l was 19 (11-59) and 30 d (14 not reached) respectively. Overall survival of patients < 60 years was 57% at 4 years and event-free survival was 32%. Survival was comparable with PBSCT and BMT after BEAM (BCNU, etoposide, cytarabine, melphalan). Remarkably, haematological recovery after BAM + WB was rapid and comparable (ANC) or slightly prolonged (platelets) in comparison with BEAM + PBSCT, despite a 10-20 times lower CD34+ cell dose in the WB graft. In conclusion, transplantation of WB containing >or= 0.3 x 10(6)/kg CD34+ cells after BAM conditioning is a safe procedure, and offers a fully equivalent and less costly alternative for PBSC.

In vitro safety profile of G-CSF-mobilized whole blood after storage for 7 days in an infusable-grade L15 medium.

BACKGROUND: G-CSF-mobilized whole blood (WB) is a cost-reducing and simple alternative for peripheral blood progenitor cell transplantation. Recently, it was demonstrated that mobilized WB supplemented with Leibovitz's L15 medium permitted prolonged preservation of clonogenic cells at ambient temperature. In this study, an infusable-grade L15 medium (IG-L15) was developed, and the safety profile of mobilized WB after 7 days of storage was investigated. STUDY DESIGN AND METHODS: IG-L15 was manufactured in a closed system under good manufacturing practice conditions. Proinflammatory cytokine levels and hemolysis in mobilized WB were determined after 7 days of storage in different containers and were compared with current clinical mobilized WB values after 1 to 3 days of storage at 4 degrees C. RESULTS: IG-L15 and L15 maintained clonogenic cells equally. In the samples of mobilized WB that were returned to the patient, cytokine levels were not elevated in comparison with freshly collected mobilized WB. By using IG-L15 in polystyrene-coated cell culture bags, median (range) levels of 9.4 (2.2-69.8) pg per mL (IL-1beta), 31.6 (6.1-146.5) pg per mL (TNF-alpha), 76.9 (15.5-934.9) pg per mL (IL-6), and 7195 (104-205,600) pg per mL (IL-8) were found after 7 days. Higher cytokine levels were found with L15 and different containers. He- molysis was less than 0.5 g per dL in all cases. CONCLUSION: The storage of mobilized WB for 7 days in IG-L15 at ambient temperature is possible with adequate preservation of clonogenic cells, but cytokine levels may require plasma removal before return.