Complexities of care: Common components of models of care in geriatrics

As people age, they are more likely to have an increasing number of medical diagnoses and medications, as well as healthcare providers who care for those conditions. Health professionals caring for older adults understand that medical issues are not the sole factors in the phenomenon of this “care complexity.” Socioeconomic, cognitive, functional, and organizational factors play a significant role. Care complexity also affects family caregivers, providers, and healthcare systems and therefore society at large. The American Geriatrics Society (AGS) created a work group to review care to identify the most common components of existing healthcare models that address care complexity in older adults. This article, a product of that work group, defines care complexity in older adults, reviews healthcare models and those most common components within them and identifies potential gaps that require attention to reduce the burden of care complexity in older adults.     

Is the professional satisfaction of general internists associated with patient satisfaction?

BACKGROUND: The growth of managed care has raised a number of concerns about patient and physician satisfaction. An association between physicians’ professional satisfaction and the satisfaction of their patients could suggest new types of organizational interventions to improve the satisfaction of both. OBJECTIVE: To examine the relation between the satisfaction of general internists and their patients. DESIGN: Cross-sectional surveys of patients and physicians. SETTING: Eleven academically affiliated general internal medicine practices in the greater-Boston area. PARTICIPANTS: A random sample of English-speaking and Spanish-speaking patients (n=2,620) with at least one visit to their physician (n=166) during the preceding year. MEASUREMENTS: Patients’ overall satisfaction with their health care, and their satisfaction with their most recent physician visit. MAIN RESULTS: After adjustment, the patients of physicians who rated themselves to be very or extremely satisfied with their work had higher scores for overall satisfaction with their health care (regression coefficient 2.10; 95% confidence interval 0.73–3.48), and for satisfaction with their most recent physician visit (regression coefficient 1.23; 95% confidence interval 0.26–2.21). In addition, younger patients, those with better overall health status, and those cared for by a physician who worked part-time were significantly more likely to report better satisfaction with both measures. Minority patients and those with managed care insurance also reported lower overal satisfaction. CONCLUSIONS: The patients of physicians who have higher professional satisfaction may themselves be more satisfied with their care. Further research will need to consider factors that may mediate the relation between patient and physician satisfaction. This work was supported by a grant from the Harvard Risk Management Foundation. Dr. Haas was the recipient of a Clinical Investigator Award from the National Institute of Child Health and Human Development (K08-HD01029) at the time that this work was initiated.     

Effects of interleukin-6 on fetal hematopoietic progenitors

Effects of interleukin-6 (IL-6) on cycling status and clonogenic maturation of human fetal (cord blood) and adult hematopoietic progenitors were compared. Adult marrow cells were incubated for various lengths of time with various concentrations of IL-6, in a serum- free system, after which tritiated thymidine suicide studies were performed. After incubation of 2 to 5 x 10(6) cells/mL for 4 hours in 5.0 ng IL-6/mL, increased thymidine suicide rates were observed for multipotent progenitors (CFU-Mix), granulocyte-macrophage progenitors (CFU-GM), and erythroid burst-forming units (BFU-E). Similar incubations of fetal cells in IL-6 resulted in similar increases in tritiated thymidine suicide rates. In other studies, IL-6 used alone did not support colony formation from adult progenitors. However, it did support colony formation from fetal CFU-Mix (P less than .05), CFU- GM (P less than .001), and BFU-E (P less than .05). In cultures of adult progenitors, IL-6 acted synergistically with IL-3 to support CFU- Mix colony formation (P less than .001), but synergistic actions on CFU- GM and BFU-E were not seen. In contrast, IL-6 acted synergistically with IL-3 and with GM-CSF to support colony formation by fetal CFU-Mix, CFU-GM, and BFU-E. Thus, IL-6 appears to have a wider spectrum of action on fetal progenitors from cord blood than on adult progenitors; including not only the induction of cycling, but also the support of clonogenic maturation of CFU-Mix, CFU-GM, and BFU-E.     

Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA- topoisomerase II

Chromosome band 11q23 is frequently involved in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) de novo, as well as in myelodysplastic syndromes (MDS) and lymphoma. Five percent to 15% of patients treated with chemotherapy for a primary neoplasm develop therapy-related AML (t-AML) that may show rearrangements, usually translocations involving band 11q23 or, less often, 21q22. These leukemias develop after a relatively short latent period and often follow the use of drugs that inhibit the activity of DNA-topoisomerase II (topo II). We previously identified a gene, MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia), at 11q23 that is involved in the de novo leukemias. We have studied 17 patients with t-MDS/t-AML, 12 of whom had cytogenetically detectable 11q23 rearrangements. Ten of the 12 t-AML patients had received topo II inhibitors and 9 of these, all with balanced translocations of 11q23, had MLL rearrangements on Southern blot analysis. None of the patients who had not received topo II inhibitors showed an MLL rearrangement. Of the 5 patients lacking 11q23 rearrangements, some of whom had monoblastic features, none had an MLL rearrangement, although 4 had received topo II inhibitors. Our study indicates that the MLL gene rearrangements are similar both in AML that develops de novo and in t-AML. The association of exposure to topo II- reactive chemotherapy with 11q23 rearrangements involving the MLL gene in t-AML suggests that topo II may play a role in the aberrant recombination events that occur in this region both in AML de novo and in t-AML.     

Functional and phenotypic characterization of human peripheral blood stem cell harvests: a comparative analysis of cells from consecutive collections

A considerable number of patients with malignancies who are treated with high-dose therapy and hematopoietic stem cell transplantation subsequently relapse. Analyses of peripheral blood stem cell (PBSC) harvests obtained from 49 cancer patients showed that the PBSC harvest contained precursors for antitumor effector cells. Ex vivo manipulation of these harvests to maximize the antitumor effector cell activity may provide a new therapeutic approach to decrease or eliminate any minimal residual disease that remains after high-dose therapy. Characterization of PBSC from consecutive collections determined the collections best suited for ex vivo augmentation of antitumor cytotoxic effector cells. We report the results of a functional and phenotypical characterization of PBSC obtained from six consecutive collections from 18 cancer patients receiving granulocyte-macrophage colony-stimulating factor (GM- CSF) for hematopoietic stem/progenitor cell mobilization. The PBSC were evaluated for their cytotoxicity using the 51Cr-release assay. The frequency and subsets of lymphocytes were determined using flow cytometry with appropriate specific marker antibodies and differential cell counts. The content of hematopoietic progenitor cells in each collection was determined using a colony-forming unit granulocyte- macrophage (CFU-GM) culture assay. The frequency of cytotoxic effector cells including lymphokine-activated killer (LAK) cell precursors and lymphocytes was significantly greater (P < .05) in the early collections, whereas the later collections contained significantly (P < .05) more CFU-GM progenitor cells and fewer cytotoxic effector cells. Thus, our results show that PBSC obtained from advanced cancer patients do contain considerable levels of precursor cells for the generation of LAK cell populations. These results suggest that cells from the earlier collections are best suited for ex vivo manipulation to augment the antitumor effects.     

Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites

A major unresolved question for 11q23 translocations involving MLL is the chromosomal mechanism(s) leading to these translocations. We have mapped breakpoints within the 8.3-kb BamHI breakpoint cluster region in 31 patients with acute lymphoblastic leukemia and acute myeloid leukemia (AML) de novo and in 8 t-AML patients. In 23 of 31 leukemia de novo patients, MLL breakpoints mapped to the centromeric half (4.57 kb) of the breakpoint cluster region, whereas those in eight de novo patients mapped to the telomeric half (3.87 kb). In contrast, only two t-AML breakpoints mapped in the centromeric half, whereas six mapped in the telomeric half. The difference in distribution of the leukemia de novo breakpoints is statistically significant (P = .02). A similar difference in distribution of breakpoints between de novo patients and t-AML patients has been reported by others. We identified a low- or weak-affinity scaffold attachment region (SAR) mapping just centromeric to the breakpoint cluster region, and a high-affinity SAR mapping within the telomeric half of the breakpoint cluster region. Using high stringency criteria to define in vitro vertebrate topoisomerase II (topo II) consensus sites, one topo II site mapped adjacent to the telomeric SAR, whereas six mapped within the SAR. Therefore, 74% of leukemia de novo and 25% of t-AML breakpoints map to the centromeric half of the breakpoint cluster region map between the two SARs; in contrast, 26% of the leukemia de novo and 75% of the t-AML patient breakpoints map to the telomeric half of the breakpoint cluster region that contains both the telomeric SAR and the topo II sites. Thus, the chromatin structure of the MLL breakpoint cluster region may be important in determining the distribution of the breakpoints. The data suggest that the mechanism(s) leading to translocations may differ in leukemia de novo and in t-AML.     

Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: comparison of immunologic properties with interleukin-2

Two human melanoma cell lines were transduced with the human interleukin (IL)-7 and IL-2 genes using retroviral-mediated gene transfer. Stable, high-level cytokine expression was achieved. The in vitro growth of transduced tumors was unaltered. Neither of the IL-2- transduced melanoma cell lines grew in athymic mice, whereas one IL-7- transduced melanoma line showed retarded in vivo growth. This is consistent with animal studies suggesting a predominantly T-cell response to IL-7-transduced tumors and a more nonspecific response to IL-2-transduced tumors. Both IL-7- and IL-2-transduced melanoma cell lines could induce cytotoxic lymphocytes in mixed lymphocyte-tumor cultures. The expression of putative melanoma antigens (MAGE)-1 and MAGE-3 was unaltered by cytokine transduction. In one cell line, IL-7 transduction resulted in a marked inhibition of the immunosuppressive peptide transforming growth factor (TGF)beta 1. The results allow a comparison of immunobiologic properties of IL-7- and IL-2-transduced human melanoma cell lines in consideration of their use in genetically engineered tumor vaccines. IL-7 transduction results in stable cytokine expression and phenotypic alterations that appear to be favorable for enhanced immunogenicity and it deserves clinical testing.     

Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis

The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement.     

Increased HbF in sickle cell anemia is determined by a factor linked to the beta S gene from one parent

Members of 7 large families, containing 20 patients with sickle cell anemia (SS) characterized by high levels of fetal hemoglobin (HbF), were studied using immunofluorescence to count F cells and a radioimmunoassay to measure small amounts of HbF. In five of these families, one of the sickle cell trait (AS) parents had a much higher HbF and F-cell count than the other; in one family, both parents had a marked increase in HbF and F cells; in the remaining family, HbF and F cells were at borderline values in both parents. Seven of 14 AS siblings, but only 1 of 8 normal hemoglobin (AA) siblings, also had HbF and F-cell counts above the "normal" range. It seems that a factor for increased F cells, linked to the beta S gene of one parent, is segregating in these families and is responsible for the greatly increased HbF and F cells in the SS subjects. HbF per F cell in AS parents and siblings was the same as that of normal AA subjects, whereas in the SS offspring it was greatly increased, suggesting that it was the result of marrow hyperplasia associated with their hemolytic anemia. The similarity of this "increased F-cell gene" to heterocellular hereditary persistence of fetal hemoglobin (HPFH). Swiss type, is discussed, and it is suggested that it may control the persistent synthesis of HbF in sickle cell anemia by its presence in early infancy.