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The objective of this study was to explore nurses' perceptions of end-of-life care following the withdrawal of the Liverpool Care Pathway (LCP). Thirteen semi-structured interviews were conducted with nurses working in palliative care. Data were analysed using thematic analysis. Three themes emerged: perceptions of the LCP, prevailing issues, and patients' and families' experiences. This study suggested that the removal of the pathway has not remedied the issues attributed to it. Further, the way in which the LCP was removed indicates that the non-expert media can play a negative role in how palliative care is perceived, which inhibits the care process. In this respect it is important that ‘insider’ voices are also heard, in order to educate and also redress disinformation. Similarly, broader, persisting, contextual challenges facing staff need addressing in order to prevent a repeat of the issues leading to the removal of the LCP.

Cross-sectional.To evaluate the accuracy with which physical therapists identify fear-avoidance beliefs in patients with low back pain by comparing therapist ratings of perceived patient fear-avoidance to the Fear-Avoidance Beliefs Questionnaire (FABQ), Tampa Scale of Kinesiophobia 11-item (TSK-11), and Pain Catastrophizing Scale (PCS). To compare the concurrent validity of therapist ratings of perceived patient fear-avoidance and a 2-item questionnaire on fear of physical activity and harm, with clinical measures of fear-avoidance (FABQ, TSK-11, PCS), pain intensity as assessed with a numeric pain rating scale (NPRS), and disability as assessed with the Oswestry Disability Questionnaire (ODQ).The need to consider psychosocial factors for identifying patients at risk for disability and chronic low back pain has been well documented. Yet the ability of physical therapists to identify fear-avoidance beliefs using direct observation has not been studied.Eight physical therapists and 80 patients with low back pain from 3 physical therapy clinics participated in the study. Patients completed the FABQ, TSK-11, PCS, ODQ, NPRS, and a dichotomous 2-item fear-avoidance screening questionnaire. Following the initial evaluation, physical therapists rated perceived patient fear-avoidance on a 0-to-10 scale and recorded 2 influences on their ratings. Spearman correlation and independent t tests determined the level of association of therapist 0-to-10 ratings and 2-item screening with fear-avoidance and clinical measures.Therapist ratings of perceived patient fear-avoidance had fair to moderate interrater reliability (ICC2,1 = 0.663). Therapist ratings did not strongly correlate with FABQ or TSK-11 scores. Instead, they unexpectedly had stronger associations with ODQ and PCS scores. Both 2-item screening questions were associated with FABQ-physical activity scores, while the fear of physical activity question was also associated with FABQ-work, TSK-11, PCS, and ODQ scores.Therapists' ratings of perceived patient fear-avoidance were not associated with self-reported fear-avoidance scores, showing a potential disconnect between therapist judgments and commonly used fear-avoidance measures. Instead, therapist ratings had small but statistically significant correlations with pain catastrophizing and disability, findings that may support therapists' inability to discriminate fear-avoidance from these other factors. The 2-item screening questions based on fear of physical activity and harm showed potential to identify elevated FABQ physical activity scores.Differential diagnosis, level 2b.

Donor lymphocyte infusions (DLI) can induce remissions in patients who have relapsed after allogeneic bone marrow transplantation (BMT). However, DLI frequently also result in significant acute and/or chronic graft-versus-host disease (GVHD). Several clinical and experimental lines of evidence have suggested that CD8+ T cells play a critical role in the pathogenesis of GVHD. To develop methods to reduce the incidence of GVHD associated with DLI, we administered defined numbers of CD4+ donor T cells after ex vivo depletion of CD8+ lymphocytes to 40 patients with relapsed hematologic malignancies after allogeneic BMT. Cohorts of patients received 0.3, 1.0, or 1.5 × 108CD4+ cells/kg. Overall, 12 of 38 patients (32%) evaluable for toxicity developed acute or chronic GVHD. However, 6 of 27 patients (22%) receiving 0.3 × 108 CD4 cells/kg developed GVHD compared with 6 of 11 patients (55%) who received ≥1.0 × 108 CD4 cells/kg (P = .07). Treatment-related mortality was low (3%), with 1 death related to infection in the setting of immunosuppression for GVHD. Disease responses after CD4+ DLI were documented in 15 of 19 patients (79%) with early-phase chronic myelogenous leukemia (CML) relapse, 5 of 6 patients (83%) with relapsed multiple myeloma, and 1 patient with myelodysplasia. For patients with early-phase CML relapse, the Kaplan-Meier probability of achieving complete cytogenetic remission was 87% and the probability of complete molecular response was 78% at 1 year after DLI. The median time to complete cytogenetic response and molecular response in patients with CML was 13 weeks (range, 9 to 30 weeks) and 34 weeks (range, 10 to 56 weeks), respectively. The median time to response in patients with multiple myeloma was 26 weeks (range, 15 to 62 weeks). All patients in this trial who developed GVHD demonstrated tumor regression, but the presence of GVHD was not required for patients to achieve a response, because 48% of responding patients never developed evidence of GVHD. Two patients with CML who did not respond at dose level 1 subsequently achieved complete cytogenetic remission after a second infusion of CD8-depleted cells at dose level 2. In patients with evidence of mixed hematopoietic chimerism who achieved a complete remission after DLI, cytogenetic analysis of marrow cells also demonstrated conversion to complete donor hematopoiesis in all evaluable patients. These studies suggest that relatively low numbers of CD8-depleted donor lymphocytes are effective in inducing complete remissions in patients with stable-phase CML and multiple myeloma who have relapsed after allogeneic BMT. Because of the relatively low risk of toxicity associated with the infusion of defined numbers of CD4+donor cells, further studies can be undertaken in the setting of persistent minimal residual disease to prevent relapse after allogeneic BMT.

The clinical efficacy of donor lymphocyte infusions (DLI) in patients with relapsed chronic myelocytic leukemia after allogeneic bone marrow transplantation has been demonstrated in several recent studies. Although it is presumed that allogeneic T cells mediate this graft-versus-leukemia (GVL) effect, the influence of DLI on the T cell compartment of recipients has not been determined. To characterize the immunologic effects of DLI and to identify T cell changes selectively associated with the GVL response, we analyzed the T cell receptor (TCR) repertoire in four patients with relapsed chronic myelocytic leukemia who achieved a complete remission after infusion of CD4+ lymphocytes from HLA-identical sibling donors. Only one of the four patients developed clinically significant graft-versus-host disease (GVHD) after infusion of donor lymphocytes. TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies in serial samples obtained over a 1-yr period before and after DLI. Results were compared to 10 normal donors. Before DLI, all four patients were found to have abnormal TCR Vbeta repertoire in peripheral T cells, associated with a large number of clonal and oligoclonal patterns. Abnormal TCR patterns persisted for at least 3 mo after DLI, but thereafter gradually began to normalize. By 1 yr after DLI, all patients demonstrated almost complete normalization of Vbeta repertoire with polyclonal representation within almost all Vbeta gene subfamilies. We also examined changes in the TCR Vbeta repertoire associated with the disappearance of Ph+ cells. In each patient, we were able to identify the expansion of at least 1 Vbeta gene subfamily that coincided with the time of the cytogenetic response. In one patient who was studied in greater detail, CDR3 size analysis of serial samples after DLI indicated that these changes were associated with the appearance of clonal T cells. This finding was confirmed through CDR3 sequence analysis and use of CDR3 clone-specific oligonucleotide probes. A putative GVL clone identified by this technique was not detectable in either donor or patient T cells before DLI, but persisted in peripheral T cells for approximately 1 yr. These experiments therefore provide evidence for the clonal expansion of allogeneic T cells that may be selective mediators of antileukemia activity without also mediating graft-versus-host disease.