Nurses as a source of system-level resilience: Secondary analysis of qualitative data from a study of intravenous infusion safety in English hospitals.

BACKGROUND: Deviations from local policy and national recommended best practice are common in the administration of intravenous infusions, but not all result in negative consequences. Some are the result of nurses' clinical judgement. However, little is known about such practices and their effects on the safety of intravenous infusions. Our objective was to explore ways in which nurses contribute to system-level resilience when administering intravenous infusions. METHODS: We conducted a secondary analysis of qualitative data from debriefs and focus groups from a mixed methods study of errors and policy deviations in intravenous infusion administration across 16 English hospitals. Analysis focused on nurses' contributions to system-level resilience, drawing on Larcos's et al. framework of types of resilience. RESULTS: Five types of system-level resilience were identified in nurses' behaviour: anticipatory resilience, responsive resilience, resilience based on past experience, workarounds and nurses performing informal 'risk assessments' in relation to how best to treat individual patients. Examples of practices contributing to infusion safety were found for each of these types of resilience. CONCLUSION: Our findings suggest nurses are a key source of system-level resilience. Some behaviours that may be considered deviations from policy or best practice are the result of reasoned clinical judgement to improve infusion safety in response to the specific situation at hand. Adaptive behaviour is necessary to cope with the complexity of practice. There is a tension between standardisation and supporting flexibility in safety management.

Systematic review: psychosocial factors associated with pain in inflammatory bowel disease.

BACKGROUND: Pain is a frequently reported symptom of inflammatory bowel disease (IBD) experienced by patients in active disease and remission. Psychological factors play a significant role in pain, but have not been systematically reviewed in IBD. AIM: To review psychosocial factors associated with pain in adults diagnosed with IBD. METHODS: Electronic (PsycInfo, MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science), and hand-searching were conducted February-May 2017. Two authors carried out screening and data extraction. RESULTS: Fifteen studies including 5539 IBD patients were identified. Emotional, cognitive-behavioural and personality factors were associated with IBD-pain. Depression and anxiety were the most commonly explored constructs, followed by perceived stress and pain catastrophising, all of which were positively associated with greater pain. Greater abdominal pain was associated with a concurrent mood disorder over fivefold (OR 5.76, 95% CI 1.39, 23.89). Coping strategies and pain fear avoidance correlated with pain levels. Perceived social support (r = .26) and internal locus of control (r = .33) correlated with less pain. Patients reporting pain in IBD remission more frequently had an existing diagnosis of a mood disorder, a chronic pain disorder and irritable bowel syndrome. Six studies controlled for disease activity, of which 4 found that psychosocial factors significantly predicted pain. The majority of studies (n = 10) were of high quality. CONCLUSION: Psychosocial factors appear to play a significant role in IBD-pain. Further research is required to explore psychosocial constructs in relation to IBD-pain, with use of validated pain measures, large sample sizes and clearer characterisation of disease activity.

Patient-controlled analgesia infusion pumps for adults.

Patient-controlled analgesia (PCA) via an infusion pump enables patients experiencing pain as a result of surgery, trauma or acute exacerbation of chronic conditions, to administer their own analgesia. Opioids are commonly used in the pumps because of their effectiveness and availability. This article, one of series on pain, describes the main features of opioid PCA, highlighting potential risks associated with this method of drug administration and common side effects of opioids. The article emphasises the importance of educating patients in PCA use to maintain safety. It is suggested that nurses must provide the same level of care to patients using PCA as patients receiving analgesia by other means.

Care of the patient receiving epidural analgesia.

Epidural analgesia is a common technique used to manage acute pain after major surgery and is viewed as the 'gold standard'. When managed effectively, epidural analgesia is known to reduce the risk of adverse outcomes following major surgery. There are two main classes of medications used in epidural analgesia: opioids and local anaesthetics. Both of these drugs are beneficial in reducing or eliminating pain, but are also responsible for the common side effects associated with this method of pain relief. There are also some rare and potentially fatal side effects of epidural therapy. The nurse's role is to assess and monitor patients carefully and report and respond to any concerns.

Pre-operative information and patient-controlled analgesia: much ado about nothing.

We examined whether pre-operative information benefited patients receiving patient-controlled analgesia (PCA) after major surgery. We investigated whether patients felt better informed about PCA and also whether pre-operative information altered the use of PCA, the adequacy of pain relief, worries about addiction and safety, and knowledge of side-effects. We investigated the effectiveness of information provided in two ways, namely by a patient-determined leaflet or an interview by a trained nurse from the pain team, compared with routine pre-operative information. We studied 225 patients, 75 in each group. Patients in the leaflet group were better informed about PCA, became familiar with using PCA more quickly and were less confused about PCA than the control group. However, there were no effects on pain relief, worries about addiction and safety, and knowledge of side effects. The pre-operative interview resulted in no benefits. Our findings indicate that the detailed provision of pre-operative information failed to improve patients' experiences of PCA.

Why do patients feel positive about patient-controlled analgesia?

We studied 200 patients to identify the aspects of their experience of patient-controlled analgesia (PCA) that made them feel 'extremely positive' about this technique. After PCA had been withdrawn, patients completed a questionnaire which included the following topics: pre-operative information, pain relief, the degree of control that PCA afforded the patient, side-effects and safety. Multiple regression analysis identified three factors of their experience which were associated uniquely with feeling 'extremely positive' about PCA: having better pain relief, not worrying about 'giving oneself too much drug' and not experiencing feeling 'peculiar in the head'. Control over pain relief, although highly correlated with feeling 'extremely positive' about PCA, was unimportant when these variables were controlled. Because of the well-recognised difficulties in measuring satisfaction with analgesic regimens, we suggest that a satisfaction score based on these variables would be a significant advance on existing methods.

Patient-controlled analgesia: an assessment by 200 patients.

Two hundred patients completed a questionnaire about their experiences of patient-controlled analgesia. The questionnaire covered the following topics: pre-operative information, reasons for pressing and not pressing the button, pain relief, side-effects, safety, advantages and disadvantages of patient-controlled analgesia, worries associated with its use and control over pain. A high level of satisfaction with the device, together with a view that it afforded control over pain, emerged from replies to simple, general questions. However, more detailed questions revealed side-effects and fears that constrained its use and hence patients' ability to control pain. Control is predominantly a feature of the professional's view of patient-controlled analgesia, rather than the patient's experience of this analgesic technique.

Generation of an antibody to HLA-G in transgenic mice and demonstration of the tissue reactivity of this antibody.

A method was devised to generate antibodies against the non-classical class I HLA-G antigen. This consisted of immunising HLA-A2/beta 2m double transgenic mice with HLA-G transfected into mouse Ltk- cells. A polyclonal antibody was obtained which appears to be specific for HLA-G. The staining pattern of this antibody was restricted solely to all populations of extravillous trophoblast. No fetal tissues reacted with this antibody, including those where HLA-G mRNA has been demonstrated, such as fetal eye, thymus and liver. This study confirms that HLA-G is a trophoblast-specific protein, although it remains a possibility that the technique of immunohistology is not sufficiently sensitive to detect low level HLA-G antigen expression in non-trophoblast tissues.

Resistance of HLA-G and HLA-A2 transfectants to lysis by decidual NK cells.

Trophoblast cells from normal first trimester pregnancies have been shown to express the nonclassical Class I molecule, HLA-G, which is nonpolymorphic and has a heavy chain of 40 kDa. These HLA-G-expressing trophoblast cells infiltrate into maternal decidua, which contains abundant uterine-specific CD56bright natural killer (NK) cells. We believe HLA-G may act as a protective molecule against decidual NK lysis and thus allow trophoblast survival in the maternal tissues. To test this hypothesis, we have constructed HLA-G and HLA-A2 transfectants using LCL 721.221 HLA-null cells. We observed that both of these antigens protected target cells from NK effectors isolated from decidua or peripheral blood, although the effect of HLA-G is not as marked as that of HLA-A2. Our results, therefore, show that in this experimental system expression of a nonclassical Class 1 HLA molecule is also correlated with NK resistance in the same way as a classical Class I HLA molecule.

In situ hybridization and northern blot demonstration of HLA-G mRNA in human trophoblast populations by locus-specific oligonucleotide.

Trophoblast cells from normal first trimester pregnancies have been shown to express the nonclassical class I molecule, HLA-G, which is nonpolymorphic and has a heavy chain of 40 kD. In this study, in situ hybridization experiments were performed using a biotinylated HLA-G specific oligonucleotide on sections of normal placenta including the implantation site. HLA-G mRNA was identified in all extravillous trophoblast populations including the cytotrophoblast cell columns, interstitial trophoblast, endovascular trophoblast, and placental bed giant cells. In addition, villous cytotrophoblast and villous mesenchymal cells also contained HLA-G transcripts, but villous syncytiotrophoblast was always negative.

Expression of the colony stimulating factor-1 receptor (c-fms product) by cells at the human uteroplacental interface.

BACKGROUND: The hematopoietic growth factor colony-stimulating factor-1 (CSF-1) and its receptor (encoded by the proto-oncogene c-fms) are implicated in the regulation of human placental development. EXPERIMENTAL DESIGN: In this study, we have performed a detailed immunohistochemical localization of the CSF-1 receptor (CSF-1R) on cells of the uteroplacental interface in human first trimester pregnancy, supplemented by Northern blot, in situ hybridization, and flow cytometric analysis. CSF-1R expression by JEG-3 and JAR choriocarcinoma cells was also investigated. RESULTS: c-fms mRNA was detected in primary cultures of first trimester trophoblast and was localized to the extravillous cytotrophoblast columns streaming off the anchoring villi. CSF-1R was expressed by fetal Hofbauer cells in the mesenchyme of the chorionic villi, and this expression increased considerably from first trimester to term. No expression was seen on first trimester and term villous cytotrophoblast. CSF-1R expression on villous syncytiotrophoblast was absent at 6 weeks, strongest at 8-10 weeks, and faded by 12 weeks. First trimester extravillous cytotrophoblast columns were strongly and consistently positive for CSF-1R expression, as was the superficial shell of extravillous trophoblast over the maternal decidua. However, with deeper invasion and terminal differentiation into placental bed giant cells, this expression became weak or absent. Endovascular trophoblast was also only weakly positive for CSF-1R. At the implantation site itself, large numbers of decidual macrophages and CD3-, CD56bright large granular lymphocytes were seen. The macrophages expressed CSF-1R strongly, but large granular lymphocytes, decidual stromal cells, glandular epithelium, and endothelial cells were found to be negative for CSF-1R expression. No CSF-1R expression was detected in JAR choriocarcinoma cells, but CSF-1R was present in first trimester cultured trophoblast and JEG-3 choriocarcinoma cells, although this was shown to be intracellular. CONCLUSIONS: These results suggest that CSF-1 may regulate invasion and differentiation of human placental trophoblast, depending upon the spatial and temporal distribution of its receptor. CSF-1 may also influence placental development and function by acting via decidual and fetal macrophages, which are the other cell populations expressing the receptor.

Human extravillous trophoblast MHC class I expression is resistant to regulation by interferon-alpha.

We have shown that MHC Class I antigen expression by first trimester human extravillous trophoblast cells is resistant to upregulation by IFN-alpha while embryonic fibroblasts of the same gestational age are responsive. This is in contrast to our previous finding that IFN-gamma increases both Class I mRNA and surface expression in these trophoblast cells. It would appear that human trophoblast has differential susceptibility to the effects of the two classes of IFN.

Interferon-gamma enhances mRNA and surface expression of class I antigen on human extravillous trophoblast.

Human trophoblast cells with immunocytochemical characteristics of the extravillous population have been isolated from 1st trimester placentae. Treatment of these cells with IFN-gamma increases the expression of Class I antigens at both the cell surface and mRNA level. A similar increase in Class I antigens is also found in JEG-3 choriocarcinoma cells after treatment with IFN-gamma. The possibility that aberrant production of IFN-gamma may upset the fetal-maternal equilibrium in vivo is discussed.

Identification of class I MHC mRNA in human first trimester trophoblast cells by in situ hybridization.

Special gestation-related regulatory mechanisms for the expression of class I Ag by trophoblast cells directly exposed to maternal blood and tissues may be required for semiallogeneic pregnancy to be successful. Analysis of class I MHC mRNA by in situ hybridization and class I MHC Ag by immunohistology has revealed two phenotypically distinct subpopulations of trophoblast cells in term placentas and extraplacental membranes. Trophoblast cells external to the placenta are mRNA +/Ag+. They contain class I mRNA and express class I Ag that differ serologically from HLA-A,B,C. In contrast, trophoblast cells forming the syncytial layer of placental villi are mRNA-/Ag-. By immunohistology, trophoblast cells in 1st trimester placental tissues are similar to those in term tissues. In our study, in situ hybridization was used to determine if patterns of trophoblast cell class I mRNA were the same or different. Trophoblast cells external to the placental villi in 1st trimester tissues contained class I mRNA as would be predicted from the results with term tissues. Unexpectedly, class I mRNA was found in villous trophoblast cells. Thus, these studies identified an mRNA+/Ag- trophoblast cell subpopulation. The results suggest that tissue-specific mechanisms may interfere with translation of class I mRNA in 1st trimester villous trophoblast cells and/or that the protein products of the mRNA are not identified by available mAb.

Activation of the trk oncogene by alternatively spliced muscle and non-muscle tropomyosin sequences.

We have constructed a derivative of the trk oncogene in which the cytoskeletal tropomyosin sequences are replaced with skeletal muscle alpha-tropomyosin sequences derived from the same tropomyosin gene by alternative splicing. The biochemical and biological properties of this derivative are indistinguishable from those of the naturally occurring trk oncogene. Thus activation of the oncogenic activity of trk is a function of structural features of tropomyosin which are common to both skeletal muscle and non-muscle isoforms.

Organization of the hTMnm gene. Implications for the evolution of muscle and non-muscle tropomyosins.

We have isolated clones of human genomic DNA which contain the structural elements of the hTMnm gene. In non-muscle tissue this gene produces a 2.5 kb (1 kb = 10(3) bases or base-pairs) mRNA encoding TM30nm, a 248 amino acid cytoskeletal tropomyosin. In muscle, alternative splicing of this gene results in the expression of a 1.3 kb mRNA encoding a 285 amino acid skeletal muscle alpha-tropomyosin. The hTMnm gene spans at least 42 kb of DNA and consists of 13 exons, only five of which are common to both the 2.5 kb and 1.3 kb transcripts. The boundaries of the exons giving rise to the muscle-specific isoform are identical to the base to those of other genes encoding muscle tropomyosins. A comparison of the structures of exons encoding the amino-terminal sequences of the muscle and non-muscle isoforms suggests that the hTMnm gene has evolved by a specific pattern of exon duplication with alternative splicing.

Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement.

Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.