Infant health effects of a nurse-community health worker home visitation programme: a randomized controlled trial.

BACKGROUND: Home visiting is supported as a way to improve child health and development. Home visiting has been usually provided by nurses or community health workers (CHWs). Few studies compared the child health advantages of a nurse-CHW team approach over nurse prenatal and postnatal home visiting. METHODS: A randomized trial was conducted with Medicaid-insured pregnant women in Kent County, Michigan. Pregnant women were assigned to a team intervention including nurse-CHW home visitation, or standard community care (CC) including nurse home visitation. Morbidity was assessed in 530 infants over their first 12 months of life from medical claims and reported by the mother. RESULTS: There were no differences in overall child health between the nurse-CHW intervention and the CC arm over the first year of life. There were fewer mother-reported asthma/wheezing/croup diagnostics in the team intervention group among infants whose mothers have low psychosocial resources (13% vs. 27%, P = 0.01; adjusted OR = 0.4, P = 0.01). There were no differences in diagnosed asthma/wheezing/croup documented by medical claims. There were no differences in immunizations, hospitalizations and ear infections. CONCLUSIONS: There was no strong evidence that infant health was improved by the addition of CHWs to a programme of CC that included nurse home visitation. Targeting such interventions at common health problems of infancy and childhood or at diagnosed chronic conditions may prove more successful.

In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy.

The existence of an immune based graft-versus-leukaemia (GvL) effect highlighted the prospect of managing relapsed leukaemias with T cell-based adoptive immunotherapy. Thus, various strategies have been explored for the in vitro expansion of acute myeloid leukaemia (AML)-specific T cells. In a popular approach, AML blasts have been genetically modified to express co-stimulatory molecules essential for effective T cell priming. One such tactic has been the modification of AML cells to express the B7/CD80 co-stimulatory molecule that binds to CD28 on T cells initiating events that culminate in enhanced cytokine production, proliferation and development of effector functions by T cells. The success of these strategies has been limited by difficulties in attaining sufficient transduction efficiencies and associated high levels of CD80 expression. We demonstrate that these problems can be circumvented by using anti-CD28 monoclonal antibody. Furthermore, we show that the synergistic relationship between CD80/CD28 pathway and interleukin 12 cytokine (IL-12), documented in the generation of cytotoxic T lymphocytes (CTL) for solid tumours, also applies to AML. CD28/IL-12 synergy facilitated the proliferation of allogeneic T cells in response to stimulation with primary AML blasts. The synergy also favoured generation of a Th1-type immune response, evidenced by gamma interferon (IFN-gamma) secretion and facilitated naive and memory T cell proliferation. Unlike some methods of in vitro T cell expansion, use of CD28/IL-12 synergy left T cells in the physiologically appropriate CD45RA-/CCR7- subsets known to be associated with immediate cytotoxic functions.

Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function--implications for the adoptive immunotherapy of leukaemia.

Evidence of an immune mediated graft-versus-leukaemia effect has led to the belief that T and NK cell based adoptive immunotherapy can constitute effective treatment for relapsed leukaemias. However, work on solid tumours has shown this strategy may be hampered, by an immune escape mechanism in which tumour secreted immunosuppressive factors compromise T and NK cell function. Indeed, acute myeloid leukaemia (AML) cells secrete immunosuppressive factors that block the synthesis of Th1 type cytokines in T cells. We demonstrate here that this immunosuppression, mediated by both HL60 AML cell line and primary AML blasts, inhibits T and NK cell proliferation but not cytolytic activity. Supernatants from HL60 cell line and primary AML blasts inhibited T cell proliferation to mitogenic and alloantigen stimulation but had no effect on cytolytic function. Similarly, the proliferation of NK cells to IL-2 and IL-15 stimulation was inhibited whilst their cytolytic function, shown by lysis of AML blasts, K562 and Daudi cells remained unaffected. The failure of T and NK cells to proliferate was not due to effector cell apoptosis. Indeed, removal of lymphocytes from the immunosuppressive environment partially restored their capacity to respond to mitogenic stimulation. T cells exposed to immunosuppressive supernatants did not increase expression of mitotic inhibitory proteins that arrest cell division, thereby ruling this out as a mechanism of operation for this immunosuppression. T cell expansion requires antigen stimulation, usually provided in the form of AML blasts, therefore our data suggest that NK cells may be more practical for the immunotherapy of AML.

Efficacy of cytokine gene transfection may differ for autologous and allogeneic tumour cell vaccines.

Whole tumour cells are a logical basis for generating immunity against the cancers they comprise or represent. A number of human trials have been initiated using cytokine-transfected whole tumour cells of autologous (patient-derived) or allogeneic [major histocompatibility complex (MHC)-disparate] origin as vaccines. Although precedent exists for the efficacy of autologous-transfected cell vaccines in animal models, little preclinical evidence confirms that these findings will extrapolate to allogeneic-transfected cell vaccines. In order to address this issue a murine melanoma cell line (K1735) was transfected to secrete interleukin (IL)-2, IL-4, IL-7 or granulocyte-macrophage colony-stimulating factor (GM-CSF); cytokines currently in use in trials. The efficacy of these cells as irradiated vaccines was tested head-to-head in syngeneic (C3H) mice and in MHC-disparate (C57BL/6) mice, the former being subsequently challenged with K1735 cells and the latter with naturally cross-reactive B16-F10 melanoma cells. Whilst the GM-CSF-secreting vaccine was the most effective at generating protection in C3H mice, little enhancement in protection above the wild-type vaccine was seen with any of the transfections for the allogeneic vaccines, even though the wild-type vaccine was more effective than the autologous B16-F10 vaccine. Anti-tumour cytotoxic T-lymphocyte (CTL) activity was detected in both models but did not correlate well with protection, whilst in vitro anti-tumour interferon-gamma (IFN-gamma) secretion tended to be higher following the GM-CSF-secreting vaccine. Cytokine transfection of vaccines generally increased anti-tumour CTL activity and IFN-gamma secretion (T helper type 1 response). Further studies in other model systems are required to confirm this apparent lack of benefit of cytokine transduction over wild-type allogeneic vaccines, and to determine which in vitro assays will correlate best with protection in vivo.

Community health workers: examining the Helper Therapy principle.

A community approach to the integration of health and social services for low-income pregnant women is being addressed through Community Integrated Service System (CISS) initiatives of the Maternal Child Health Bureau. This particular CISS program model was designed to enable low-income mothers to function in a Community Health Worker (CHW) role providing social support for at-risk pregnant women. Using Riessman's notion of "helper therapy," the model was also developed to enhance the potential for CHWs to gain helper benefits. The purpose of this exploratory study was to describe perceived helper benefits and stressors associated with the CHW role and to examine the usefulness of an instrument developed to assess benefits and stressors. The study findings revealed that the majority of CHWs perceived helper benefits that included positive feelings about self, a sense of belonging, valuable work experience, and access to health information and skills through training or contact with program staff. Stressors such as feeling inadequate to help, however, were associated with the helper role for some CHWs. Preliminary analysis of the Helper's Perception Measure indicated that it may be an effective measure and should be tested with a larger sample of CHWs.

Parent-to-parent support initiated in the neonatal intensive care unit.

A preliminary quasi-experimental, longitudinal study was conducted to explore differences in maternal mood states, self-esteem, family functioning, maternal-infant interaction, and home environment between mothers of preterm infants who participated in a nurse-managed program of parent-to-parent support and those who served as a comparison group. Mothers who participated in the intervention scored significantly higher on the Barnard NCATS interaction measure and the HOME total scale and subscales of maternal responsiveness and organization (N = 58) at 12 months following discharge from a neonatal intensive care unit. Using repeated measures analysis for a subset of mothers (n = 32), there were significant differences between the two groups on the mood state anxiety-tension (POMS) during the first 4 months postdischarge, with the treatment group having less anxiety. There was also a group by time interaction effect on self-esteem during the first 4 months, with self-esteem of the treatment group mothers increasing and comparison mothers decreasing. Findings suggest that one-to-one veteran parent support, in a nurse-managed program, may influence maternal and maternal-infant interaction outcomes.

Creative caring in the NICU: parent-to-parent support.

When infants are admitted to a neonatal intensive care unit, the parents are immediately confronted with the crisis surrounding a critically ill newborn and often require additional support. Parents experience feelings of anxiety, fear, anger, and guilt over this unanticipated event. In addition, parents often describe the withdrawal of friends and the denial responses of well-meaning family members during their infant's illness. In an effort to address the NICU parents' need for support, Butterworth Hospital in collaboration with Michigan State University initiated a demonstration and research project focused on parent-to-parent support. The primary goal of the program is to improve parenting outcomes by providing emotional, informational, and role modeling support to parents of high-risk infants utilizing experienced volunteer parents. The program model includes professional program coordinators who recruit and train volunteer parents with past NICU experience. Volunteers are then matched to new NICU families based on infant's diagnosis, similar geographic location, and other characteristics. Volunteers provide support through hospital visits, phone contact, and home visits during the infant's hospitalization and throughout the infant's first year of life. The program was evaluated by analyzing the differences between a treatment group and a comparison group of parents. Significant differences between groups were found on measures of maternal mood states, maternal-infant relationships, and home environment. Services to over 900 families by 110 volunteer parents have convinced staff that the volunteer parents are a valuable and indispensable component of the services at Butterworth Hospital and that families of high-risk infants benefit from past experiences and ongoing support of volunteer parents.

Exogenous interleukin regulates growth of C6 tumors in vivo.

Elvax pellets containing interleukin 1 (IL-1) or 2 (IL-2) were assessed for their ability to alter the growth of transplanted C6 cells in rat. C6 cells were injected into the left caudate of Sprague Dawley rats. At the time of tumor cell injection, or 9 days later, Elvax pellets containing either 50 or 200 units of interleukin were inserted into the dorsal aspect of the caudate. Animals were killed 16 days later and the volume of tumors determined. Results showed that introduction of low-dose IL-2 pellets at time of C6 cell injection virtually prevented establishment of tumors, whereas low-dose IL-1 pellet insertion resulted in nearly a threefold increase in tumor size relative to control preparations. Insertion of high-dose IL-2 pellets 9 days after C6 cell injection decreased tumor growth relative to controls by nearly twofold, low-dose pellets having no effect. These effects appear to be mediated by alterations in host brains, vs interleukin-moderating effects on growth of C6 cells themselves, since (a) no effect of IL-2 on C6 cell growth in vitro could be demonstrated and IL-1 appeared to enhance their proliferation in culture, and (b) IL-1 pellets diminished and IL-2 pellets enhanced infiltration of inflammatory cells into brain when implanted into brain after a "stab" wound.