A UK survey of the impact of cancer on employment.

BACKGROUND: Improvements in cancer detection and treatment and an increase in retirement age mean more people may experience cancer during their working lives. AIMS: To examine the impact of cancer on work activities, sources of advice and support for return-to-work decisions and the role of employers in supporting employees with cancer. METHODS: A cross-sectional survey of a randomly selected sample of people from two cancer registries was conducted in England. Eligible individuals were invited to participate via their general practitioners (April-October 2011) and completed a questionnaire online or by telephone interview. Survey weights were applied before statistical analysis, ensuring responses were representative of cancer survivors in the random sample. RESULTS: A total of 382 people completed the survey, 27% of those invited to participate. Full-time employment fell from 53% prior to diagnosis to 33% after diagnosis, and average working hours reduced from 38 to 32h per week. Only 48% discussed employment issues with their oncology treatment team, and this was associated with more hours worked (36.7 versus 29.4h). Seventy-six per cent of employers were perceived to have been very supportive and 56% receptive to a phased return-to-work. CONCLUSIONS: This is one of the largest UK registry-based surveys on this subject. Following treatment for cancer, there were significant falls in full-time working and hours worked. Just under half the sample discussed employment issues with their treatment team, and these participants worked significantly more hours. This indicates scope for improvement such as encouraging health professionals to raise work-related issues within time-limited consultations.

Nanolitre liquid patterning in aqueous environments for spatially defined reagent delivery to mammalian cells.

Microscale biopatterning enables regulation of cell-material interactions and cell shape, and enables multiplexed high-throughput studies in a cell- and reagent-efficient manner. The majority of available techniques rely on physical contact of a stamp, pin, or mask with mainly a dry surface. Inkjet and piezoelectric printing is carried out in a non-contact manner but still requires a substantially dry substrate to ensure fidelity of printed patterns. These existing methods, therefore, are limited for patterning onto delicate surfaces of living cells because physical contact or substantially dry conditions are damaging to them. Microfluidic patterning with laminar streams does enable non-contact patterning in fully aqueous environments but with limited throughput and reagent diffusion across interfacial flows. Here, we describe a polymeric aqueous two-phase system that enables patterning nanolitres of a reagent-containing aqueous phase, in arbitrary shapes, within a second aqueous phase covering a cell monolayer. With the appropriate medium formulation, reagents of interest remain confined to the patterned phase without significant diffusion. The fully aqueous environment ensures high reagent activity and cell viability. The utility of this strategy is demonstrated with patterned delivery of genetic materials to mammalian cells for phenotypic screening of gene expression and gene silencing.

Economic evaluation of a randomized clinical trial of hospital versus telephone follow-up after treatment for breast cancer.

BACKGROUND: This was an economic evaluation of hospital versus telephone follow-up by specialist nurses after treatment for breast cancer. METHODS: A cost minimization analysis was carried out from a National Health Service (NHS) perspective using data from a trial in which 374 women were randomized to telephone or hospital follow-up. Primary analysis compared NHS resource use for routine follow-up over a mean of 24 months. Secondary analyses included patient and carer travel and productivity costs, and NHS and personal social services costs of care in patients with recurrent breast cancer. RESULTS: Patients who had telephone follow-up had approximately 20 per cent more consultations (634 versus 524). The longer duration of telephone consultations and the frequent use of junior medical staff in hospital clinics resulted in higher routine costs for telephone follow-up (mean difference pound 55 (bias-corrected 95 per cent confidence interval (b.c.i.) pound 29 to pound 77)). There were no significant differences in the costs of treating recurrence, but patients who had hospital-based follow-up had significantly higher travel and productivity costs (mean difference pound 47 (95 per cent b.c.i. pound 40 to pound 55)). CONCLUSION: Telephone follow-up for breast cancer may reduce the burden on busy hospital clinics but will not necessarily lead to cost or salary savings.

Can lay people deliver asthma self-management education as effectively as primary care based practice nurses?

OBJECTIVES: To determine whether well trained lay people could deliver asthma self-management education with comparable outcomes to that achieved by primary care based practice nurses. DESIGN: Randomised equivalence trial. SETTING: 39 general practices in West London and North West England. PARTICIPANTS: 567 patients with asthma who were on regular maintenance therapy. 15 lay educators were recruited and trained to deliver asthma self-management education. INTERVENTION: An initial consultation of up to 45 min offered either by a lay educator or a practice based primary care nurse, followed by a second shorter face to face consultation and telephone follow-up for 1 year. MAIN OUTCOME MEASURES: Unscheduled need for healthcare. SECONDARY OUTCOME MEASURES: Patient satisfaction and need for courses of oral steroids. RESULTS: 567 patients were randomised to care by a nurse (n = 287) or a lay educator (n = 280) and 146 and 171, respectively, attended the first face to face educational session. During the first two consultations, management changes were made in 35/146 patients seen by a practice nurse (24.0%) and in 56/171 patients (32.7%) seen by a lay educator. For 418/567 patients (73.7%), we have 1 year data on use of unscheduled healthcare. Under an intention to treat approach, 61/205 patients (29.8%) in the nurse led group required unscheduled care compared with 65/213 (30.5%) in the lay led group (90% CI for difference -8.1% to 6.6%; 95% CI for difference -9.5% to 8.0%). The 90% CI contained the predetermined equivalence region (-5% to +5%) giving an inconclusive result regarding the equivalence of the two approaches. Despite the fact that all patients had been prescribed regular maintenance therapy, 122/418 patients (29.2%) required courses of steroid tablets during the course of 1 year. Patient satisfaction following the initial face to face consultation was similar in both groups. CONCLUSIONS: It is possible to recruit and train lay educators to deliver a discrete area of respiratory care, with comparable outcomes to those seen by nurses.

Overexpression of IRF9 confers resistance to antimicrotubule agents in breast cancer cells.

IRF9/p48/ISGF3gamma (IRF9) is an IFN regulatory factor that mediates signaling by type I IFNs (IFNalpha and IFNbeta). After single-step selection of breast adenocarcinoma cells in paclitaxel, differential display and single gene analysis demonstrated that transcriptional activation of IRF9 and other IFN-responsive genes, independent of IFN, corresponded with resistance to antimicrotubule agents. Transient overexpression of IRF9 reproduced the drug-resistance phenotype and induced expression of IFN-responsive genes. However, drug resistance was not induced by overexpression of Stat1 or Stat2, or treatment with IFNalpha per se. Using a donor-matched array of cDNA prepared from human tumor and normal tissue from a variety of organs, we observed overexpression of IRF9 in approximately one-half of breast and uterine tumors, which indicated that IRF9 may be important in signaling in these tumor types. These data identify a novel IFN-independent role for IRF9 in the development of resistance to antimicrotubule agents in breast tumor cells and may link downstream mediators of IFN signaling to drug resistance in human cancers.

Endothelial CXCR7 regulates breast cancer metastasis.

Atypical chemokine receptor CXCR7 (ACKR3) functions as a scavenger receptor for chemokine CXCL12, a molecule that promotes multiple steps in tumor growth and metastasis in breast cancer and multiple other malignancies. Although normal vascular endothelium expresses low levels of CXCR7, marked upregulation of CXCR7 occurs in tumor vasculature in breast cancer and other tumors. To investigate effects of endothelial CXCR7 in breast cancer, we conditionally deleted this receptor from vascular endothelium of adult mice, generating CXCR7(ΔEND/ΔEND) animals. CXCR7(ΔEND/ΔEND) mice appeared phenotypically normal, although these animals exhibited a modest 35±3% increase in plasma CXCL12 as compared with control. Using two different syngeneic, orthotopic tumor implant models of breast cancer, we discovered that CXCR7(ΔEND/ΔEND) mice had significantly greater local recurrence of cancer following resection, elevated numbers of circulating tumor cells and more spontaneous metastases. CXCR7(ΔEND/ΔEND) mice also showed greater experimental metastases following intracardiac injection of cancer cells. These results establish that endothelial CXCR7 limits breast cancer metastasis at multiple steps in the metastatic cascade, advancing understanding of CXCL12 pathways in tumor environments and informing ongoing drug development targeting CXCR7 in cancer.

Development and evaluation of an intervention to support family caregivers of people with cancer to provide home-based care at the end of life: a feasibility study.

PURPOSE: To design and evaluate an intervention to address carers' needs for practical information and support skills when caring for a person with cancer at end of life. METHOD: Phase I 29 carers were interviewed about need for practical information, support skills and their preferences for information delivery. The preferred format was a booklet. Phase 2 evaluated the booklet. 31 carers and 14 district nurses participated. Validated questionnaires: on perceptions of caregiving and carer health before and after the booklet was used and interviews with both carers and nurses were untertaken.24 carers completed both interviews. Quantitative data were coded using scale manuals and analysed using SPSSv20 and interview data was analysed thematically. RESULTS: Carers were aged 31-82 and cared for people aged 50-92; 8 carers were male and 23 female; 20 cared for a partner, 8 for a parent and 1 for a sibling (2 undisclosed). Carers were positive about the booklet, however many carers would have liked the booklet earlier. Carers reported feeling more positive about caregiving, and more reassured and competent in their role. District nurses found the booklet useful and reported receiving fewer phone calls from study carers than others in similar situations. CONCLUSIONS: The booklet intervention was a source of reassurance to carers and it has the potential to be incorporated into everyday practice. The challenge is in when and how to distribute the booklet and more work is required on the timing of delivery in order to maximise the usefulness of booklet to carers.

CXCL12-γ in primary tumors drives breast cancer metastasis.

Compelling evidence shows that chemokine C-X-C motif chemokine ligand 12 (CXCL12) drives metastasis in multiple malignancies. Similar to other key cytokines in cancer, CXCL12 exists as several isoforms with distinct biophysical properties that may alter signaling and functional outputs. However, effects of CXCL12 isoforms in cancer remain unknown. CXCL12-α, -ß and -γ showed cell-type-specific differences in activating signaling through G protein-dependent pathways in cell-based assays, while CXCL12-γ had greatest effects on recruitment of the adapter protein ß-arrestin 2. CXCL12-ß and -γ also stimulated endothelial tube formation to a greater extent than CXCL12-α. To investigate the effects of CXCL12 isoforms on tumor growth and metastasis, we used a mouse xenograft model of metastatic human breast cancer combining CXCR4+ breast cancer cells and mammary fibroblasts secreting an isoform of CXCL12. Altough all CXCL12 isoforms produced comparable growth of mammary tumors, CXCL12-γ significantly increased metastasis to bone marrow and other sites. Breast cancer cells originating from tumors with CXCL12-γ fibroblasts upregulated RANKL (receptor activator of nuclear factor-κB ligand), contributing to bone marrow tropism of metastatic cancer cells. CXCL12-γ was expressed in metastatic tissues in mice, and we also detected CXCL12-γ in malignant pleural effusions from patients with breast cancer. In our mouse model, mammary fibroblasts disseminated to sites of breast cancer metastases, providing another mechanism to increase levels of CXCL12 in metastatic environments. These studies identify CXCL12-γ as a potent pro-metastatic molecule with important implications for cancer biology and effective therapeutic targeting of CXCL12 pathways.

Comparative study reveals better far-red fluorescent protein for whole body imaging.

Genetically encoded far-red and near-infrared fluorescent proteins enable efficient imaging in studies of tumorigenesis, embryogenesis, and inflammation in model animals. Here we report comparative testing of available GFP-like far-red fluorescent proteins along with a modified protein, named Katushka2S, and near-infrared bacterial phytochrome-based markers. We compare fluorescence signal and signal-to-noise ratio at various excitation wavelength and emission filter combinations using transiently transfected cell implants in mice, providing a basis for rational choice of optimal marker(s) for in vivo imaging studies. We demonstrate that the signals of various far-red fluorescent proteins can be spectrally unmixed based on different signal-to-noise ratios in different channels, providing the straightforward possibility of multiplexed imaging with standard equipment. Katushka2S produced the brightest and fastest maturing fluorescence in all experimental setups. At the same time, signal-to-noise ratios for Katushka2S and near-infrared bacterial phytochrome, iRFP720 were comparable in their optimal channels. Distinct spectral and genetic characteristics suggest this pair of a far-red and a near-infrared fluorescent protein as an optimal combination for dual color, whole body imaging studies in model animals.

Kinetic analysis of plasmepsins I and II aspartic proteases of the Plasmodium falciparum digestive vacuole.

Plasmepsins I and II are Plasmodium falciparum aspartic proteases implicated in hemoglobin degradation. Using a synthetic fluorogenic peptide substrate based on the initial hemoglobin cleavage site, we have analyzed kinetic parameters of the two enzymes in native and recombinant forms. Both native plasmepsins cleave the model substrate well. Recombinant plasmepsin II behaves similarly to native enzyme, substantiating its usefulness for inhibition and structural studies. In contrast, recombinant plasmepsin I does not resemble its native homolog kinetically. A hybrid molecule, in which the polyproline loop of plasmepsin I has been replaced by the homologous sequence from plasmepsin II, still maintains the specificity/kinetics of plasmepsin II. This suggests that the polyproline loop, important for substrate recognition in the mammalian aspartic protease renin, does not play a similar role in the plasmepsins.

Effects of MDR1 and MDR3 P-glycoproteins, MRP1, and BCRP/MXR/ABCP on the transport of (99m)Tc-tetrofosmin.

Multidrug resistance (MDR1) P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and breast cancer resistance protein (BCRP/MXR/ABCP) are members of the ATP-binding-cassette (ABC) superfamily of membrane transporters and are thought to function as energy-dependent efflux pumps of a variety of structurally diverse chemotherapeutic agents. We herein report the characterization of (99m)Tc-Tetrofosmin, a candidate radiopharmaceutical substrate of ABC transporters. (99m)Tc-Tetrofosmin showed high membrane potential-dependent accumulation in drug-sensitive KB 3-1 cells and low antagonist-reversible accumulation in MDR KB 8-5 and KB 8-5-11 cells in proportion to levels of MDR1 Pgp expression. In KB 8-5 cells, EC(50) values of the potent MDR antagonists N-(4-[2-(1,2,3, 4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9, 10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), (2R)-anti-5-¿3-[4-(10, 11-difluoromethanodibenzo-suber-5-yl)piperazin-1-yl]-2 -hydroxypropoxy ¿quinoline trihydrochloride (LY335979), and (3'-keto-Bmt')-[Val(2)]-cyclosporin A (PSC 833) were 40, 66, and 986 nM, respectively. Furthermore, only baculoviruses carrying human MDR1, but not MDR3, conferred both a decrease in accumulation of (99m)Tc-Tetrofosmin in host Spodoptera frugiperda (Sf9) cells and a GF120918-induced enhancement. Transport studies with a variety of stably transfected and drug-selected tumor cell lines were performed with (99m)Tc-Tetrofosmin and compared with (99m)Tc-Sestamibi, a previously validated MDR imaging agent. MDR1 Pgp readily transported each agent. To a lesser extent, MRP1 also transported each agent, likely as co-transport substrates with GSH; neither agent was a substrate for the BCRP/MXR/ABCP half-transporter. In mdr1a(-/-) and mdr1a/1b(-/-) mice, (99m)Tc-Tetrofosmin showed approximately 3. 5-fold greater brain uptake and retention compared with wild-type, with no net change in blood pharmacokinetics, consistent with transport in vivo by Pgp expressed at the capillary blood-brain barrier. Molecular imaging of the functional transport activity of ABC transporters in vivo with (99m)Tc-Tetrofosmin and related radiopharmaceuticals may enable non-invasive monitoring of chemotherapeutic and MDR gene therapy protocols.

Readability of patient information booklets for women with breast cancer.

Providing accurate information, in both verbal and written formats, is seen as an important component of patient care. For individuals diagnosed with cancer, acquiring information may be a particularly pertinent issue in terms of coping with the disease. Numerous information booklets are available for people with cancer which aim to provide information on various aspects of care and treatment. This British study examined the readability of 50 information booklets available to women with breast cancer using the SMOG and Flesch reading tests. Generally the information booklets were found to have a high reading age, arguably not suitable for the majority of the United Kingdom (UK) population. This study has implications for health care professionals who provide written information as a supplement or substitute for verbal information.

Treatment decision making in women newly diagnosed with breast cancer.

The purpose of this study was to explore the hypothesis that women with breast cancer had specific preferences about the degree of control they wanted over treatment decision making. One hundred fifty women, newly diagnosed with breast cancer, were interviewed and their preferences for participation in treatment decision making were established using a measurement tool designed to elicit decision-making preferences (Degner LF, Sloan JF. Decision making during serious illness: What role do patients really want to play? J Clin Epidemiol 1992;45:944-50). Two hundred women with benign breast disease served as a descriptive comparison group. Unfolding theory (Coombs CH. A theory of data. New York: John Wiley & Sons, 1964) provided a means of analyzing the data so that the degree of control preferred by each woman could be established. The majority of the newly diagnosed women preferred to play a passive role in treatment decision making, leaving the decision-making responsibility to their physician, whereas the benign control group preferred a collaborative role in which joint decisions could be made between the patient and the physician. The implications of the results for patient participation are discussed.

Palliative care: community nurses' perceptions of quality.

OBJECTIVES: To identify community nurses' perceptions of quality care provision for patients requiring palliative care. DESIGN: Semi-structured interviews were conducted with community nurses working within the district nursing service. An adaptation of Flanagan's critical incident technique was employed to elicit factors associated with high or poor quality palliative care. Interviews were tape recorded and transcribed. Data were analysed using thematic content analysis, recurrent themes being agreed by the research team. SETTING: One community healthcare trust. SUBJECTS: 62 members of the district nursing team (grades B-H). RESULTS: Respondents recounted the context in which high quality palliative care could be provided, the actions required, and the indicators that suggested the desired level of care had been achieved. Key factors identified were: the early referral of patients to the district nursing service, family circumstances, the availability of time, the accessibility of services and equipment, and the relationship with other healthcare professionals and informal carers. There was a general view that a positive outcome had been achieved when patients retained control over their circumstances and died a peaceful death, in the place of their choice, supported by their family. CONCLUSIONS: Community nurses were able to articulate clearly the essential components of high quality care. Whilst these factors do not represent a comprehensive list, they are put forward as a useful starting point for standard setting and subsequent audit.

An exploration of midwives' attitudes to research and perceived barriers to research utilisation.

OBJECTIVE: To explore midwives' views about research and their perceived barriers to research utilisation. SETTING: Thirty-two midwives from four midwifery units in the north west of England. The units ranged in size from a small district unit (52 midwives, and 1200 deliveries per annum), to a large regional centre (290 midwives, 6500 deliveries per annum). METHODS: Midwives' opinions concerning research were explored using focus group interviews; within the interviews midwives were asked to discuss how they viewed the relevance of research to midwifery care, the constraints which they felt prevented them from delivering research-based care and existing and potential methods of disseminating research. FINDINGS: There was a consensus among the midwives that they aspired to deliver research-based care. However, there are clearly a number of barriers preventing this. Research was poorly accessible to most midwives, both in terms of its physical location and complexity. Furthermore, midwives felt they lacked the knowledge and skills to appraise research, and lacked the confidence to judge when research should be implemented. CONCLUSIONS: The current trend to demedicalise childbirth demands that midwives become proficient users of research. However, the means of disseminating research findings to midwives in the north west of England does not meet their needs.

Reading nursing: the burden of being different.

The data on which this paper is based were collected by means of informal interviews with final year nursing undergraduates at one university. From students' accounts it is apparent that the lives of undergraduate nurses are dominated by an all embracing feeling of 'difference'. This paper centres on the theme of 'difference' and draws upon the literature from the field of disablement in an attempt to explain the position of undergraduate nurses.

The response of nurses towards the management and teaching of patients on continuous ambulatory peritoneal dialysis (CAPD).

The aim of this paper is to shed some light on the way trained nurses responded to the challenge of teaching patients to manage life on Continuous Ambulatory Peritoneal Dialysis (CAPD). This topic is of interest since nursing skills and knowledge are central to the successful management of patients on CAPD. More importantly, the treatment has the potential to keep patients alive who would not previously have been treated. Hence the assumption underpinning this work is that the opinions which nurses hold regarding this form of treatment may in due course influence its future. The data on which this paper is based were collected by means of participant observation over a period of nine months on one male and one female medical ward. Supplementary data were collected during this time at the out-patient clinic and at multidisciplinary CAPD meetings. The findings reported here are impressionistic and hypothesis-generating, but nevertheless they do provide sound insights into the way nurses reacted to patients on this new form of treatment. The type of patient selected for treatment and the ward workload were found to be the most influential factors in the way nurses regarded CAPD patients. It seemed that patients were viewed as 'members' of a collectivity rather than as individuals. Hence the job of the nurse was to rationalize competing demands on her time. Our data suggest that nurses viewed CAPD patients as generating 'extra work' and these patients were more likely to be viewed unfavourably.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluating computer assisted learning for renal patients.

Healthcare professionals have become increasingly concerned with evaluating the impact of their interventions. Consumerism, quality initiatives and financial constraints have contributed in large measure to this concern. Consequently, the focus of many studies which involve the introduction of new and untried techniques is often on demonstrating their relative usefulness. This study sought to evaluate the usefulness and acceptability of computer assisted learning (CAL) for use in the education of renal patients on continuous ambulatory peritoneal dialysis. However, several problems were encountered which limited or impaired the evaluation process. We describe these problems and use them to illustrate the difficulties inherent in evaluative research.

Changes in patterns of knowing the patient: the case of British district nurses.

British district or home nurses, have until recent years been hidden from the wider context of the British National Health Service. Policy changes in UK over the last two decades of the 20th century have increasingly focussed on Primary Care Services and district nurses (DNs) have seen substantial changes to their workload. This paper addresses the question of how the changes in the organisation of Primary Care Services affected some aspects of DNs' work. Thus, the focus of this paper is an examination of the relationship DNs had with patients through a period of turbulent change. Knowing the patient is a central element of nursing practice. Data are presented here form a multi-site ethnographic study of DNs' work undertaken in four purposively sampled study sites. Applying Carper's (1978) framework, the data presented here show that there has been a shifting emphasis in knowing the patient from aesthetic and personal knowing to knowing about and empirical knowing.

The referral process in health visiting.

The aim of this paper is to explore the concept of referral as it emerged from an in-depth qualitative study of health visiting practice. The study was conducted using a grounded theory approach to data collection and analysis (Glaser and Strauss, 1967). Forty-five experienced health visitors were interviewed using a semi-structured interview guide. The interviews were tape recorded and later transcribed. A detailed analysis is presented of the processes involved in referring. This includes working up the client for referral, working up the agency, third party referrals, and issues of control in the referral process. The outcome of referral in terms of the effect on the client is also discussed. This paper makes a contribution to our understanding of the microprocesses in everyday health visiting practice.