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.

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.

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.

Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis.

Chemokines critically regulate chemotaxis in normal and pathologic states, but there is limited understanding of how multicellular interactions generate gradients needed for cell migration. Previous studies of chemotaxis of CXCR4+ cells toward chemokine CXCL12 suggest the requirement of cells expressing scavenger receptor CXCR7 in a source-sink system. We leveraged an established microfluidic device to discover that chemotaxis of CXCR4 cells toward distinct isoforms of CXCL12 required CXCR7 scavenging only under conditions with higher than optimal levels of CXCL12. Chemotaxis toward CXCL12-ß and -γ isoforms, which have greater binding to extracellular molecules and have been largely overlooked, was less dependent on CXCR7 than the more commonly studied CXCL12-α. Chemotaxis of CXCR4+ cells toward even low levels of CXCL12-γ and CXCL12-ß still occurred during treatment with a FDA-approved inhibitor of CXCR4. We also detected CXCL12-γ only in breast cancers from patients with advanced disease. Physiological gradient formation within the device facilitated interrogation of key differences in chemotaxis among CXCL12 isoforms and suggests CXCL12-γ as a biomarker for metastatic cancer.

Predictors of outcomes of recovery following total hip replacement surgery: A prospective study.

OBJECTIVES: To investigate psychosocial and biomedical outcomes following total hip replacement (THR) and to identify predictors of recovery from THR. METHODS: Patients with osteoarthritis (OA) on the waiting list for primary THR in North West England were assessed pre-operatively and at six and 12 months post-operatively to investigate psychosocial and biomedical outcomes. Psychosocial outcomes were anxiety and depression, social support and health-related quality of life (HRQoL). Biomedical outcomes were pain, physical function and stiffness. The primary outcome was the Short-Form 36 (SF-36) Health Survey Total Physical Function. Potential predictors of outcome were age, sex, body mass index, previous joint replacement, involvement in the decision for THR, any comorbidities, any complications, type of medication, and pre-operative ENRICHD Social Support Instrument score, Hospital Anxiety and Depression scores and Western Ontario and McMaster Universities osteoarthritis index score. RESULTS: The study included 206 patients undergoing THR. There were 88 men and 118 women with a mean age of 66.3 years (sd 10.4;36 to 89). Pain, stiffness and physical function, severity of OA, HRQoL, anxiety and depression all improved significantly from pre-operative to 12-month assessment (all p < 0.001), with the greatest improvement occurring in the first six months (all p < 0.001). The predictors that were found to influence recovery six months after THR were: pain (p < 0.001), anxiety (p = 0.034), depression (p = 0.001), previous joint replacement (p = 0.006) and anti-inflammatory drugs (p = 0.012). CONCLUSIONS: The study identified the key psychosocial and biomedical predictors of recovery following THR. By identifying these predictors, we are able to identify and provide more support for patients at risk of poor recovery following THR. Cite this article: Bone Joint Res 2013;2:248-54.

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.

Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CXCR4-positive breast cancer cells.

Chemokine CXCL12 and receptor CXCR4 control multiple steps in primary tumor growth and metastasis in breast cancer and more than 20 other human malignancies. Mechanisms that regulate availability of CXCL12 in tumor microenvironments will substantially impact cancer progression and ongoing efforts to target the CXCL12-CXCR4 pathway for cancer chemotherapy. We used dual luciferase imaging to investigate CXCR7-dependent scavenging of CXCL12 in breast tumors in vivo and quantify effects of CXCR7 on tumor growth and metastasis of a separate population of CXCR4+ breast cancer cells. In a mouse xenograft model of human breast cancer, in vivo imaging showed that malignant cells expressing CXCR7 reduced bioluminescent CXCL12 secreted in the primary tumor microenvironment. Capitalizing on sensitive detection of bioluminescent CXCL12, we also demonstrated that CXCR7+ cells reduced amounts of chemokine released from orthotopic tumors into the circulation. Immunofluorescence staining of human primary breast cancers showed expression of CXCR4 and CXCR7 on malignant cells in ≈30% of cases. In most cases, CXCR4 and CXCR7 predominantly were expressed on separate populations of malignant cells in a tumor. We modeled these cases of human breast cancer by co-implanting tumor xenografts with CXCR4+ breast cancer cells, human mammary fibroblasts secreting CXCL12, and CXCR7+ or control breast cancer cells. Bioluminescence imaging showed that CXCR7+ breast cancer cells enhanced proliferation of CXCR4+ breast cancer cells in orthotopic tumors and spontaneous metastases. Treatment with a small-molecule inhibitor of CXCR7 chemokine limited the growth of CXCR4+ breast cancer cells in tumors that also contained malignant CXCR7+ cells. These studies establish a new in vivo imaging method to quantify chemokine scavenging by CXCR7 in the tumor microenvironment and identify that CXCR7+ cells promote growth and metastasis of CXCR4+ breast cancer cells.

Colorectal cancer follow-up: patient satisfaction and amenability to telephone after care.

PURPOSE: To explore patient satisfaction on different aspects of follow-up service provision following treatment for colorectal cancer and amenability to an alternative strategy for follow-up care. METHODS AND SAMPLE: A postal survey was administered to 297 eligible patients who had been treated for colorectal cancer at a large hospital in the North West of England. Patients were asked to indicate responses to questions comprising likert scales, including views on organisation of care, information and advice, personal experience of care, satisfaction with information and care, views on specialist nursing services and amenability to telephone follow-up. KEY RESULTS: One hundred and eighty-seven completed surveys were returned (62.97% response rate). Analysis of scale data indicated high levels of satisfaction on all outcome measures but sub-optimal rates of satisfaction on some items. Respondents indicated high levels of satisfaction with information related to disease and treatment but lower levels of satisfaction for items related to genetic risk, sexual attractiveness and self care. Colorectal nurse specialists were highly rated, especially in terms of information provision and personal experience of care. Patients were generally amenable to telephone follow-up, although male patients indicated higher levels of willingness to accept this approach than females. CONCLUSIONS: Satisfaction with traditional medical based follow-up is generally high in this patient cohort but there is room for improvement in terms of service delivery. High levels of satisfaction with the care delivered by colorectal nurse specialists and patient acceptance of telephone follow-up suggests nurse-led telephone follow-up is a viable alternative to traditional hospital based follow-up.

Exploring the needs, concerns and behaviours of people with existing respiratory conditions in relation to the H1N1 'swine influenza' pandemic: a multicentre survey and qualitative study.

BACKGROUND: People with respiratory conditions are a 'high-risk' group for H1N1 pandemic swine influenza ('swine flu'), hence they and their families may have information needs, worries and concerns regarding the condition. Health-related behaviours, including vaccination, are recommended during the pandemic; understanding uptake of these is important. OBJECTIVES: To explore and compare information needs, worries and concerns, and health-related behaviours regarding swine flu in people with respiratory conditions and their family members. METHODS: Mixed-methods study - cross-sectional survey (253 patients, 101 family members); one-to-one interviews (13 patients, seven family members) and focus groups (n = three groups, 30 participants). Data collected October 2009-January 2010 from hospital chest clinics (n = 7) and patient support groups (n = 10) in North West England. RESULTS: Most patients (P) and family members (FM) wanted more information (n = 158, 62.5% P; n = 55, 54.4% FM), but few felt completely uninformed (n = 15, 5.9% P; n = 3, 3.0% FM). Most had already received information about swine flu (n = 187, 73.9% P; n = 78, 77.2% FM), mainly via a leaflet delivered to their home (n = 125, 49.4% P; n = 55, 54.5% FM). Information received was considered helpful (n = 154, 60.9% P; n = 77, 72.6% FM), but many wanted more condition-specific information (n = 141, 55.7% P; n = 60, 59.4% FM). More patients were worried (n = 147, 58.3%) than not worried (n = 99, 39.3%) about swine flu. FM were less often concerned about personal risk (n = 47, 46.6% worried) than about risk to patients (n = 76, 77.6%). Two-thirds (n = 161, 63.6% P; 65, 65.6% FM) incorrectly believed patients had increased risk of developing swine flu, but most (n = 204, 81.0% P; 89, 89.9% FM) correctly identified patients' greater risk of developing complications. Commonly adopted preventative measures were more frequent hand-washing (107, 42.8% P; 38, 37.6% FM) and greater use of sanitising hand gel (n = 100, 40.5% P; 37, 36.6% FM). In total, 212 patients (83.8%) and 69 family members (68.3%) were very/fairly likely to take up swine flu vaccination. Qualitative data mirrored survey findings. CONCLUSIONS: Participants were generally well-informed about swine flu, but more targeted information would have been welcomed. Participants were not highly anxious about swine flu, but did recognise risks for patients. Behaviour change was modest, but in line with recommendations. Vaccination intent was high. STUDY REGISTRATION: The study has been registered as REC/IRAS (Ref 09/H1015/76) and NIHR CSP (Ref 32483).

Constitutive and chemokine-dependent internalization and recycling of CXCR7 in breast cancer cells to degrade chemokine ligands.

CXCR7 is a receptor for chemokines including CXCL12 (stromal-derived factor-1), a molecule that promotes tumor growth and metastasis in breast cancer and other malignancies. Building on the recent observation that CXCR7 sequesters CXCL12, we investigated mechanisms for CXCR7-dependent uptake of chemokines. Breast cancer cells expressing CXCR7 accumulated chemokines CXCL12 and CXC11 present at concentrations <1 ng/ml, unlike cells expressing CXCR4. CXCR7-dependent accumulation of chemokines was reduced by inhibitors of clathrin-mediated endocytosis. After CXCR7-mediated internalization, CXCL12 trafficked to lysosomes and was degraded, although levels of CXCR7 remained stable. CXCR7 reduced CXCL12 in the extracellular space, limiting the amounts of chemokine available to acutely stimulate signaling through CXCR4. CXCR7 constitutively internalized and recycled to the cell membrane even in the absence of ligand, and addition of chemokines did not significantly enhance receptor internalization. Chemokines at concentrations less than the Kd values for ligand-receptor binding did not alter levels of CXCR7 at the cell surface. Higher concentrations of chemokine ligands reduced the total cell surface expression of CXCR7 without affecting receptor internalization, indicating that receptor recycling was inhibited. CXCR7-dependent uptake of chemokines and receptor trafficking were regulated by beta-arrestin 2. These studies establish mechanisms through which CXCR7 regulates the availability of chemokine ligands in the extracellular space.

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.

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.

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.

A longitudinal study exploring pain control, treatment and service provision for individuals with end-stage lower limb osteoarthritis.

OBJECTIVE: To investigate the level of pain control, treatment and service provision amongst individuals with end-stage lower limb osteoarthritis who were on the waiting list for hip or knee joint replacement. METHODS: A total of 105 patients on a waiting list for primary knee or hip replacement from a regional orthopaedic centre in the UK were recruited. The study was longitudinal and based on direct interviews at baseline and 6 months, with a postal questionnaire at 3 months. Data were collected on pain by a visual analogue scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. In addition, medication and the use of services and treatments were recorded. RESULTS: Participants experienced high levels of pain as measured by VAS [mean 7.0; 95% confidence interval (CI) 6.6-7.5] and WOMAC pain (mean 11.2; 95% CI 10.6-11.9). The majority of participants (78, 74%) was taking analgesics more than once a day. Primary care utilization was variable. Of the 74 (70%) participants who had consulted their GP in the previous 3 months, 41 (55%) had not discussed their pain or osteoarthritis during these consultations. Just below one-third of participants (31, 30%) reported to have received information on osteoarthritis. CONCLUSIONS: Pain appears to be difficult to manage in individuals with end-stage lower limb osteoarthritis. Individuals appeared not to be taking appropriate levels of analgesia in relation to levels of pain. Improvements are required in the provision of information on pain and osteoarthritis. Patients would benefit from more proactive management by health professionals (especially by GPs).

Supportive care in the cancer setting: rhetoric or reality?

BACKGROUND: Since 1995, UK cancer policy has been directed at organizational changes to secure improvements in treatment outcomes and quality of supportive care for cancer patients. The substantial increase in hospital-based specialist cancer nurses (SCNs) during this time suggests they have a major role to play in the delivery of supportive care. AIM: To explore how SCNs implemented their role in the context of organizational change and newly-formed multidisciplinary teams. METHODS: Twenty-nine SCNs participated in observation and/or interviews, resulting in 135 hours of observation and in-depth semi-structured interviews with 17 SCNs. Data were collected and analysed using a grounded theory approach. RESULTS: The prominence of the treatment agenda--the process of investigating, diagnosing and treating cancer--presented the biggest challenge to the delivery of supportive care. The treatment agenda influenced how support was offered, determined professional boundaries and relegated support to a subordinate position in patient care. CONCLUSIONS: Access to supportive care is a central tenet of current cancer policy and crucial to the philosophy of patient-centred care. While SCNs are essential to the delivery of supportive care, this study highlights the challenges they encounter in organizations which prioritise treatment and improvements to treatment outcomes.

Involvement in treatment decisions: what do adults with asthma want and what do they get? Results of a cross sectional survey.

BACKGROUND: Current healthcare policy advocates patient participation in treatment decision making. However, in asthma there is little evidence regarding patients' views on such involvement. This study explored the preferred and perceived level of involvement in treatment decisions, rationales for role preference, perceived facilitators of/barriers to involvement, and the interrelationship of role preference and demographic variables in a sample of patients with asthma. METHODS: A cross sectional survey was performed of 230 adults with clinician diagnosed asthma from 10 primary care sites and one specialist respiratory centre in north-west England. Preferred role in treatment decisions was assessed using the Control Preferences Scale. RESULTS: Fifty five (23.9%) preferred an active role, 82 (35.7%) a collaborative role, and 93 (40.4%) a passive role; 19 (8.2%) perceived their role as active compared with 45 (19.6%) collaborative and 166 (72.2%) passive. Only 33.5% (n = 77) of respondents attained their most preferred role; 55.2% (n = 127) were less involved than they preferred. Patient related, professional related, and organisational factors, especially quality and duration of consultations, facilitated or hampered involvement. Role preferences were not strongly associated with demographic variables or asthma severity. CONCLUSIONS: This study in patients with asthma highlights the fact that there is a need for professional and patient education regarding partnership working, skilful communication, and innovative approaches to service delivery.

Upper level of the spina bifida defect: how good are we?

OBJECTIVE: To assess the accuracy of obstetric sonography in determining the upper level of myelomeningocele lesions. METHODS: This was a retrospective study of 171 consecutive cases of spina bifida repaired in utero. The upper level of the lesion as determined by obstetric sonography was assigned by community physicians prior to referral in the second trimester and by the authors at Vanderbilt University Medical Center during preoperative evaluation. One hundred and eleven cases had levels established by plane-film X-ray or magnetic resonance imaging after delivery and this was regarded as the gold standard. RESULTS: Of the 171 community examinations, only 29% identified a specific upper level of the lesion; our corresponding examinations specified the lesion level in all cases. Of the 111 cases that had upper levels of the lesion established by post-delivery imaging, corresponding levels were available for comparison from 35 of the community examinations and from 111 of the examinations performed at Vanderbilt. All three assigned levels were available for comparison in 35 cases. In 26% of cases, community-assigned levels agreed exactly with post-delivery levels, while 66% agreed within one level and 80% agreed within two levels. In 38% of cases, levels assigned at Vanderbilt agreed exactly with post-delivery levels, while 78% agreed within one level and 96% agreed within two levels. Upper levels of the lesion assigned at Vanderbilt were significantly more accurate overall compared with those assigned by community physicians (signed rank test [paired comparison], P = 0.048). However, comparison of lesion levels assigned at Vanderbilt in the first 50 vs. the last 61 cases revealed a significant learning effect (Fisher's exact test, P = 0.03). When comparison of lesion levels assigned by community physicians was restricted to the first 50 cases at Vanderbilt, accuracy was similar (n = 13; t-test, P = 0.16; rank sum test, 0.31). CONCLUSIONS: Community physicians were successful in assigning the upper level of the spina bifida lesion only 29% of the time. When successful, the accuracy of these determinations was similar to that of the authors at Vanderbilt. A significant learning effect was demonstrated by improved accuracy over time at Vanderbilt. A concerted continuing medical education effort is indicated to improve the imaging skills of physicians in the accurate diagnosis of the severity of spina bifida in fetuses.