Frequency of opioid use in a population of cancer patients during the trajectory of the disease.

AIMS: Bearing in mind that Denmark has one of the world's highest legal uses of strong opioids per capita, the aim of the present study was to describe the frequency of opioid use in a complete, population-based cohort of cancer patients at different time points during the trajectory of the disease, and to analyse the influence of different factors on opioid use close to death. MATERIALS AND METHODS: All incident cancer patients registered in 1997-1998 (n=4006) from a population of 470,000 were followed individually from diagnosis to death (non-survivors) or for 5 years (survivors). The use of opioids was obtained from a prescription database covering the whole population. RESULTS: Among the 43% cancer patients who survived for 5 years, 12% used opioids at diagnosis, 38% during follow-up and 10% after 5 years. For the non-survivors, 80% used opioids sometime during follow-up. At diagnosis, use related inversely to the cancer type's 5-year survival, and ranged from 20 to 46%; before death 64-76% used opioids. The odds ratios for opioid use at death were smaller for breast cancer (0.53; confidence interval 0.33-0.85), haemopoietic cancer (0.28; confidence interval 0.17-0.44) and the group of miscellaneous cancers (0.54; confidence interval 0.36-0.83) compared with colorectal cancer. Older age, longer disease duration and male gender (0.76; confidence interval 0.59-0.99) reduced the odds of opioid use at death. CONCLUSIONS: Judged by the use of opioids, moderate to severe pain is frequent throughout the trajectory of the cancer disease. The frequency of opioid use was in accordance with the frequency of moderate to severe cancer-related pain described in published studies. This completely population-based data set enables analyses of the actual practice regarding cancer patients' use of opioids, and it can serve as a more effective template for the management of cancer pain than the traditional measures, such as opioid consumption per capita, for international comparisons.

Subsets of CD34+ hematopoietic progenitors and platelet recovery after high dose chemotherapy and peripheral blood stem cell transplantation.

BACKGROUND AND OBJECTIVE: Randomized clinical trials have shown that peripheral blood stem cell transplantations (PBSCT) with appropriate doses of CD34+ cells are associated with rapid, complete and sustained recovery of marrow functions. Nevertheless, in a minority af patients delayed platelet recovery may occur and it remains to be established whether analysis of transplanted CD34+ cell subsets may demonstrate correlation with this phenomenon. We studied a series of 80 consecutive transplanted patients with the aim of evaluating the effect of CD34+ stem cell numbers and, in a subgroup of 32 patients, the effect of the lineage specific subset numbers on time to platelet engraftment (i.e. time to platelet counts higher than 20x10(9)/L for two consecutive days without the need for platelet transfusions). DESIGN AND METHODS: Different clinical and paraclinical factors were examined in a multivariate analysis for effect on platelet engraftment in 80 patients. RESULTS: The number of CD34+ cells/kg infused was the most important factor predicting the time to platelet engraftment. Patients receiving more than 10x10(6) CD34+ cells/kg had prompt platelet engraftment. The majority of the patients (78%) received fewer than 10x10(3) CD34+ cells/kg and 17/62 (27%) of these patients experienced delayed platelet engraftment. In 32 patients receiving fewer than 10x10(6) CD34+ cells/kg we focused on the content of different lineage specific CD34+ subsets in the PBSC products. The most significant correlation was recognized for CD34+/CD61+ megakaryocytic cell number and platelet engraftment. An inverse correlation between the CD34+/CD38Eth subset and platelet engraftment was found, indicating that a high number of CD34+/CD38Eth in the PBSC product might increase the risk for delayed engraftment. These results were further confirmed by the observation that patients who experienced platelet engraftment after day 20 had significantly more CD34+/CD38Eth cells/kg infused than patients with fast engraftment. INTERPRETATION AND CONCLUSIONS: The number of total CD34+ cells/kg infused was the most important factor predicting time to platelet engraftment. CD34+ subset analysis in a subgroup of patients suggests that a high number of uncommitted progenitors may be associated with slower platelet recovery than transplantation with a higher fraction of more committed peripheral blood stem cells.

Comparison of rhG--CSF primed bone marrow and blood stem cell autografts: an analysis of engraftment in malignant lymphomas and solid tumours.

Many studies have documented faster engraftment after transplantation with peripheral blood stem cells (PBSC) compared to bone marrow (BM) stem cells. Most comparisons, however, have been between unprimed BM and primed PBSC. We have collected engraftment data on 39 patients from 4 Danish centres and compared G-CSF primed BM with G-CSF primed PBSC in malignant lymphoma and solid tumours. In the lymphoma group 6 BM transplants were compared with 8 PBSC transplants, whereas in the testicular cancer group 16 BM transplants were compared with 9 PBSC transplants. In the lymphoma group, the time to platelet engraftment (platelets >20x10(9)/l unsupported) was median 15 d in PBSC transplants and median 34 d in BM transplants (p=0.003). In the solid tumour patients the difference in time to platelet engraftment was 11 and 18 d in PBSC and BM transplants, respectively (p<0.0001). In an attempt to explain this difference we performed CD34+ subset analysis of BM and PBSC. This analysis revealed a higher content of lineage restricted cells (CD34+CD61+ and CD34+GlyA+) in PBSC compared to BM. In conclusion, G-CSF mobilized PBSC seems to result in faster engraftment than G-CSF primed BM, which could be explained by an increased number of lineage specific progenitors in PBSC compared to BM.

Immune complex binding to erythrocyte-CR1 (CD 35), CR1 expression and levels of erythrocyte-fixed C3 fragments in SLE outpatients.

Erythrocytes (E) from a cross-sectional group of 22 outpatients with systemic lupus erythematosus (SLE) and/or mixed connective tissue disease (MCTD), the majority without active disease (n = 14), were analyzed for CR1 antigen expression and capacity to bind complement opsonized, radiolabelled immune complexes (IC). Furthermore, E-bound C3 fragments and the plasma C3d concentration were determined. E-bound C3b/iC3b fragments were not elevated in patients with SLE, whereas E from 11 out of 22 SLE patients had increased C3d levels which correlated with the plasma C3d concentration (Rs 0.73, p less than 0.001). E-fixed C3d fragments did not affect the binding of Mab or preopsonized IC to E-CR1 and were not correlated with disease activity or medical treatment. Antigen expression of E-CR1 measured by ELISA or agglutination showed positive correlation with the IC binding capacity of E-CR1 (Rs 0.92 and 0.72 respectively, p less than 001). The IC binding capacity of E-CR1 from SLE patients was significantly reduced (p less than 0.005), whereas the antigen expression of CR1 (ELISA) on E from the patients did not differ from that of E from healthy donors (p greater than 0.1). E-CR1 antigen was measured by Mab reacting with an epitope outside the IC-binding site of E-CR1. E-CR1 antigen expression or IC binding showed no correlation either with disease activity or prednisolone treatment. However, 4 og 5 patients with MCTD and 4 of 5 patients receiving Imurel were found to have low E-CR1 expression and capacity to bind IC. Thus, measurement of antigenic E-CR1 in a cross-sectional group of SLE outpatients by use of Mab reacting with an epitope outside the ligand-binding region of CR1 did not reveal a significantly reduced CR1 expression. However, an assay for CR1-mediated IC binding showed a clearly reduced E-CR1 function.

Interaction of complement-solubilized immune complexes with CR1 receptors on human erythrocytes. The binding reaction.

The binding of complement (C)-solubilized 125I bovine serum albumin (BSA) anti-BSA immune complexes (IC) to CR1 receptors on human red blood cells (RBC-CR1) was studied. The binding of IC to CR1 was strongly dependent on the molar antigen to antibody ratio, and IC formed in moderate antigen excess showed no binding. IC solubilized in 50% human serum in the presence of autologous RBC bound rapidly to RBC-CR1, with maximal binding within less than 1 min at 37 degrees C. Release of CR1-bound IC under these conditions occurred slowly, requiring more than 30 min. Only binding of 'partially' solubilized, e.g., anti C3c (C4c), and conglutinin-reactive IC occurred, whereas fully solubilized complexes (IC-C3dg, C4d) showed virtually no binding. Solubilization of IC in the presence of Mg-EGTA or in C2-deficient serum resulted in a markedly delayed binding of IC to RBC, indicating the importance of an intact classical pathway in preparing the IC for binding to RBC-CR1. C-solubilized IC could be absorbed to solid-phase conglutinin or antibody to C3c and C4c, and these ligands were able to inhibit the binding of solubilized IC to RBC. Heparin also exerted a marked, dose-dependent inhibitory effect on the binding of presolubilized IC to RBC-CR1, whereas the binding was unaffected by the addition of monosaccharides or by the concentration of Ca2+ or Mg2+ ions.