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BACKGROUND: Protein provision is thought to be integral to attenuating muscle wasting in critical illness, yet patients receive half of that prescribed. As international guidelines lack definitive evidence to support recommendations, understanding clinicians' views relating to protein practices is of importance. OBJECTIVES: The objective of this study was to describe Australia and New Zealand intensive care unit (ICU) dietitians' protein prescription and perceived delivery practices in critically ill adults, including common barriers and associations between ICU clinical experience and protein prescriptions for different clinical conditions. METHODS: A 42-item descriptive quantitative survey of Australian and New Zealand intensive care dietitians was disseminated through nutrition and ICU society e-mailing lists. Data were collected on respondent demographics and reported protein practices including questions related to a multitrauma case study. Data were analysed using descriptive and content analysis and reported as n (%). Fisher's exact tests were used to compare experience and protein prescriptions. RESULTS: Of the 67 responses received (one excluded due to >50% missing data), more than 80% of respondents stated they would prescribe 1.2-1.5 g protein/kg bodyweight/day for most critically ill patients, most commonly using European Society of Clinical Nutrition and Metabolism (ESPEN) guidelines to support prescriptions (n = 61/66, 92%). Most respondents (n = 49/66, 74%) thought their practice achieved 61-80% of protein prescriptions, with frequently reported barriers including fasting periods (n = 59/66, 89%), avoiding energy overfeeding (n = 50/66, 76%), and gastrointestinal intolerance (n = 47/66, 71%). No associations between years of ICU experience and protein prescriptions for 14 of the 15 predefined clinical conditions were present. CONCLUSIONS: Australian and New Zealand ICU dietitians use international guidelines to inform protein prescriptions of 1.2-1.5 g/kg/day for most clinical conditions, and protein prescriptions do not appear to be influenced by years of ICU experience. Key perceived barriers to protein delivery including avoidance of energy overfeeding and gastrointestinal intolerance could be explored to improve protein adequacy.

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OBJECTIVE: Homozygous mutations in the TSH beta subunit gene (TSHB) result in severe, isolated, central congenital hypothyroidism (CCH). This entity evades diagnosis in TSH-based congenital hypothyroidism (CH) screening programmes in the UK and Ireland. Accordingly, genetic diagnosis, enabling ascertainment of affected relatives in families, is critical for prompt diagnosis and treatment of the disorder. DESIGN, PATIENTS AND MEASUREMENTS: Four cases of isolated TSH deficiency from three unrelated families in the UK and Ireland were investigated for mutations or deletions in TSHB. Haplotype analysis, to investigate a founder effect, was undertaken in cases with identical mutations (c.373delT). RESULTS: Two siblings in kindred 1 were homozygous for a previously described TSHB mutation (c.373delT). In kindreds 2 and 3, the affected individuals were compound heterozygous for TSHB c.373delT and either a 5·4-kB TSHB deletion (kindred 2, c.1-4389_417*195delinsCTCA) or a novel TSHB missense mutation (kindred 3, c.2T>C, p.Met1?). Neurodevelopmental retardation, following delayed diagnosis and treatment, was present in 3 cases. In contrast, the younger sibling in kindred 1 developed normally following genetic diagnosis and treatment from birth. CONCLUSIONS: This study, including the identification of a second, novel, TSHB deletion, expands the molecular spectrum of TSHB defects and suggests that allele loss may be a commoner basis for TSH deficiency than previously suspected. Delayed diagnosis and treatment of profound central hypothyroidism in such cases result in neurodevelopmental retardation. Inclusion of thyroxine (T4) plus thyroxine-binding globulin (TBG), or free thyroxine (FT4) in CH screening, together with genetic case ascertainment enabling earlier therapeutic intervention, could prevent such adverse sequelae.

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OBJECTIVES: To evaluate the changes in prognostic impression and patient management following PET/CT in patients with vulvar and vaginal carcinoma; and to compare PET/CT findings with those of conventional imaging modalities. METHODS: We summarized prospectively and retrospectively collected data for 50 consecutive patients from our institution that enrolled in the National Oncologic PET Registry and underwent FDG-PET/CT for a suspected or known primary or recurrent vulvar/vaginal cancer. RESULTS: 54/83 (65%) studies included had a diagnosis of vulvar cancer, and the remaining 29/83 (35%), a diagnosis of vaginal cancer. Following FDG-PET/CT, the physician's prognostic impression changed in 51% of cases. A change in patient management, defined as a change to/from a non-interventional strategy (observation or additional imaging), to/from an interventional strategy (biopsy or treatment), was documented in 36% of studies. The electronic records demonstrated that 95% of the management strategies recorded in the physician questionnaires were implemented as planned. MRI and/or CT were performed within one month of the FDG-PET/CT in 20/83 (24%) and 28/83 (34%) cases, respectively. FDG-PET/CT detected nodes suspicious for metastases on 29/83 (35%) studies performed. MRI and CT detected positive nodes on 6 and 11 studies respectively. Distant metastases were identified in 10 cases imaged with FDG-PET and 5 cases that had additional conventional CT imaging. All suspicious lesions seen on CT were positively identified on PET/CT. In 4 cases, an abnormality identified on PET/CT, was not seen on diagnostic CT. CONCLUSIONS: FDG-PET/CT may play an important role in the management of vulvar and vaginal carcinoma.

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Methods for assessing the wicking properties of individual fibre bundles have been developed from models based on the original Washburn equation (WE) and the modified Washburn equation (MWE), which also accounts for swelling. Both models gave indication of differences in wicking properties of flax and the viscose fibres, though MWE gave additional information that could be interpreted in terms of the physical model. Wicking of the viscose fibres is mainly via inter-fibre capillaries while that of flax is a combination of inter-fibre capillaries and lumen present in some elementary fibres. The degree of swelling and associated rotation of flax fibre in a vapour pressure range of 1-6torr were monitored using an environmental scanning electron microscope (ESEM). Viscose fibre exhibited swelling under the same conditions but did not rotate. The two techniques highlighted different mechanisms of wicking which can be used for monitoring moisture uptake/swelling of treated fibres for fabrication of composites.

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OBJECTIVE: To evaluate clinical characteristics and outcomes in incidentally detected lung cancer and in symptomatic lung cancer. MATERIAL AND METHODS: We designed a retrospective study including all patients undergoing pulmonary resection with a curative intention for NSCLC. They were classified into two groups according to the presence or absence of cancer-related symptoms at diagnosis in asymptomatic (ASX)­incidental diagnosis­or symptomatic. RESULTS: Of the 593 patients, 320 (53.9%) were ASX. In 71.8% of these, diagnosis was made by chest X-ray. Patients in the ASX group were older (P = 0.007), had a higher prevalence of previous malignancy (P = 0.002), presented as a solitary nodule more frequently (P < 0.001), and were more likely to have earlier-stage disease and smaller cancers (P = 0.0001). A higher prevalence of incidental detection was observed in the last ten years (P = 0.008). Overall 5-year survival was higher for ASX (P = 0.001). Median survival times in pathological stages IIIB-IV were not significantly different. CONCLUSION: Incidental finding of NSCLC is not uncommon even among nonsmokers. It occurred frequently in smokers and in those with history of previous malignancy. Mortality of incidental diagnosis group was lower, but the better survival was related to the greater number of patients with earlier-stage disease.

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We have compared fetal heart rate patterns, Apgar scores and umbilical cord gas values following initiation of labour analgesia using either combined spinal-epidural or epidural. One hundred and fifteen healthy women requesting neuraxial analgesia in the first stage of labour were randomly assigned to receive either combined spinal-epidural (n = 62) or epidural analgesia (n = 53). Fetal heart rate traces, recorded for 30 min before and 60 min after neuraxial block, were categorised as normal, suspicious or pathological according to national guidelines. Sixty-one fetal heart rate tracings were analysed in the combined spinal-epidural group and 52 in the epidural group. No significant differences were found in fetal heart rate patterns, Apgar scores or umbilical artery and vein acid-base status between groups. However, in both combined spinal-epidural and epidural groups, there was a significant increase in the incidence of abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001); two before compared with eight after analgesia in the combined spinal-epidural group and zero before compared with 11 after in the epidural group. These changes comprised increased decelerations (p = 0.0045) (combined spinal-epidural group nine before and 14 after analgesia, epidural group four before and 16 after), increased late decelerations (p < 0.0001) (combined spinal-epidural group zero before and seven after analgesia, epidural group zero before and eight after), and a reduction in acceleration rate (p = 0.034) (combined spinal-epidural group mean (SD) 12.2 (6.7) h(-1) before and 9.9 (6.1) h(-1) after analgesia, epidural group 11.0 (7.3) h(-1) before and 8.4 (5.9) h(-1) after). These fetal heart rate changes did not affect neonatal outcome in this healthy population.

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How animals manage time and expend energy has implications for survivorship. Being able to measure key metabolic costs of animals under natural conditions is therefore an important tool in behavioral ecology. One method for estimating activity-specific metabolic rate is via derived measures of acceleration, often 'overall dynamic body acceleration' (ODBA), recorded by an instrumented acceleration logger. ODBA has been shown to correlate well with rate of oxygen consumption (V˙o2) in a range of species during activity in the laboratory. This study devised a method for attaching acceleration loggers to decapod crustaceans and then correlated ODBA against concurrent respirometry readings to assess accelerometry as a proxy for activity-specific energy expenditure in a model species, the American lobster Homarus americanus. Where the instrumented animals exhibited a sufficient range of activity levels, positive linear relationships were found between V˙o2 and ODBA over 20min periods at a range of ambient temperatures (6, 13 and 20°C). Mixed effect linear models based on these data and morphometrics provided reasonably strong predictive power for estimating activity-specific V˙o2 from ODBA. These V˙o2-ODBA calibrations demonstrate the potential of accelerometry as an effective predictor of behavior-specific metabolic rate of crustaceans in the wild during periods of activity.

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Labour analgesia initiated using a combined spinal-epidural (CSE) technique may reduce subsequent epidural bupivacaine requirements compared with an epidural-only technique. We compared the minimum local analgesic concentrations (MLAC) of epidural bupivacaine following initial intrathecal or epidural injection. In a prospective, double-blind study, 115 women requesting epidural analgesia were randomly assigned to receive either an epidural with bupivacaine 20 mg and fentanyl 40 µg or a CSE with intrathecal bupivacaine 2.5 mg and fentanyl 5 µg. Analgesia was assessed using a visual analogue pain score. When further analgesia was requested, bupivacaine 20 ml was given, and the concentration was determined using the technique of up-down sequential allocation. The MLAC of bupivacaine in the epidural group was 0.032% wt/vol (95% CI 0.020-0.044) compared with 0.047% wt/vol (95% CI 0.042-0.052) in the CSE group. Bupivacaine requirements for the second injection were increased following intrathecal analgesia by a factor of 1.45 (p = 0.026) compared with epidural analgesia.

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BACKGROUND: Placenta praevia and accreta are leading causes of major obstetric haemorrhage and peripartum hysterectomy. Detection is largely based on a high index of clinical suspicion, though the diagnostic accuracy of radiological imaging is improving. Interventional radiological techniques can reduce blood loss and the incidence of hysterectomy. METHODS: We have reviewed our experience with bilateral prophylactic uterine artery balloon occlusion in the management of women with suspected placenta accreta. Thirteen women at high risk of major haemorrhage due to placenta praevia or suspected placenta accreta were retrospectively studied. Uterine artery balloons were placed prophylactically under neuraxial anaesthesia in the angiography suite followed by caesarean delivery in the obstetric operating theatre. RESULTS: Intraoperative blood loss and transfusion requirements were low in our case series. There were no hysterectomies or admissions to the intensive care unit. Fetal bradycardia necessitating immediate caesarean delivery occurred in two women (15.4%). CONCLUSION: In our case series in women with suspected placenta accreta, prophylactic use of uterine artery balloons was associated with a low requirement for blood transfusion but with possible increased risk of fetal compromise. Performing the interventional procedure at a different site from the operative room complicated management.

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Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anticancer agents designed to infect and lyse tumor cells. However, in spite of their promise as selective cancer therapeutics, replicating adenoviruses have shown limited efficacy in the clinical setting. We hypothesized that a CRAd armed with osteoprotegerin (OPG) would eradicate bone metastases of breast cancer both directly, by oncolysis, and indirectly, by inhibiting osteoclastic bone resorption, and thus reducing the tumor burden. We constructed an armed CRAd (Ad5-Δ24-sOPG-Fc-RGD) by replacing viral E3B genes with a fusion of the ligand-binding domains of OPG and the Fc portion of human IgG1. Conditional replication was conferred by a 24-base pair deletion within E1A (Δ24), which prevents the binding of E1A to the retinoblastoma tumor suppressor/cell cycle regulator protein and limits replication in normal cells. Enhanced infection of cells expressing low levels of the primary Ad5 receptor was conferred by incorporating an arginine-glycine-aspartic acid (RGD) peptide sequence into the fiber knob to mediate binding to α(v) integrins. After characterization of the armed CRAd, we demonstrated that infection of breast cancer cells by Ad5-Δ24-sOPG-Fc-RGD both killed the infected cells by oncolysis and inhibited the formation of osteoclasts in an in vitro co-culture model. In a murine model of osteolytic bone metastases of breast cancer, the CRAd armed with shortened OPG (sOPG)-Fc reduced tumor burden in the bone and inhibited osteoclast formation more effectively than an unarmed CRAd.

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BACKGROUND: The aim of this study was to determine if sensory block following spinal anaesthesia, measured with a range of devices, corresponded to the hierarchy of nerve fibre size in the area of differential block, and to compare the distribution and variability of recorded measurements. METHODS: Women with singleton pregnancies > 36 weeks of gestation undergoing elective caesarean section under combined spinal-epidural anaesthesia were recruited. An identical spinal anaesthetic was given to all. A single researcher with no clinical role assessed block height at 20 min from the time of spinal injection. Six tests were used in random order to measure four sensory modalities: ethyl chloride (cold), calibrated Neuropen (sharp), standardized monofilament 10 g (pressure), Neurotip stroking (light touch), monofilament stroking (light touch), cotton wool (light touch). The cost of each method of testing was noted. RESULTS: The median differences between the four modalities were significant (Friedman test, P < 0.0001), but paired tests failed to find significant differences between Neuropen (sharp) and monofilament (pressure), monofilament (pressure) and Neurotip (light touch), and between tests for light touch. The tests for light touch had the least dermatomal spread and produced a unimodal distribution. The coefficient of variation was highest with ethyl chloride (24.1%) and the lowest with cotton wool (10.4%). CONCLUSIONS: Sensory fibre hierarchy could be identified. Tests for light touch showed the least variability. More expensive tests do not appear to have any advantage over the least expensive test, cotton wool.

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BACKGROUND: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. METHODS: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. RESULTS: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was pound59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was pound2017 where background weight gain was limited to 0.5 kg/year, and pound2651 at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. CONCLUSION: Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

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BACKGROUND: In obstetric practice use of a regional technique with a low failure rate minimises the need to convert to general anaesthesia (GA). Previous studies have suggested that combined spinal-epidural anaesthesia (CSE) has a lower GA conversion rate than spinal or epidural anaesthesia alone. In addition, a double-space CSE may be associated with fewer failures than the needle-through-needle technique. However, whether this has an effect on GA conversion rate is unknown. We aimed to review our practice of the double-space CSE technique for elective caesarean section. METHODS: Data from 3519 elective caesarean sections performed between 1999 and 2008 using the double-space CSE technique were collected retrospectively from the electronic database, original case records and annual reviews collated by the Department of Obstetric Anaesthesia, St James's University Hospital, Leeds. Complications such as conversion to GA, accidental dural puncture (ADP), post-dural-puncture headache (PDPH) and blood patching were specifically reviewed. RESULTS: The GA conversion rate in our unit was 0.23% (1:440). The ADP rate was 0.7% (1:141) with a 52% incidence of severe PDPH. The overall need for blood patching was 0.4% (1:251). One in five epidurals was supplemented during caesarean section. CONCLUSION: Compared to previously published work using spinal or needle-through-needle CSE anaesthesia we have found a lower GA conversion rate in our unit using the double-space CSE technique for elective caesarean section.

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BACKGROUND: Prophylactic infusion of phenylephrine to prevent hypotension at Caesarean section has been shown to decrease the rostral spread of intrathecal plain levobupivacaine and intrathecal hyperbaric bupivacaine by a median of two dermatomes compared with ephedrine. The aim of this study was to determine the median effective dose (ED50) of intrathecal bupivacaine required to achieve a block to touch at the xiphisternum in patients undergoing Caesarean section when phenylephrine or ephedrine are used to prevent hypotension. METHODS: Seventy women were randomized in two groups to receive either phenylephrine at a rate of 16.6 microg min(-1) (concentration 1microg ml(-1)) or ephedrine at a rate of 1.5 mg min(-1) (concentration 90 microg ml(-1)). Patients received varying doses of hyperbaric bupivacaine with fentanyl 25 microg using a double-blinded, up-down sequential allocation design. Effective doses were defined as anaesthesia to touch with ethyl chloride spray to the xiphisternum within 20 min. RESULTS: The ED50 estimates of bupivacaine were similar in the two groups: 7.8 mg [95% confidence interval (CI) 6.7-8.9] with phenylephrine and 7.6 mg (95% CI 6.8-8.4) with ephedrine. Systolic blood pressure control was similar (P=0.18) with vasopressors but heart rate was higher with ephedrine (P=0.0014). CONCLUSIONS: Under the conditions of this study, we have shown that when phenylephrine or ephedrine were used to prevent post-spinal hypotension, the dosing requirement of hyperbaric bupivacaine was similar for intrathecal anaesthesia.

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BACKGROUND: Increasing numbers of patients prescribed clopidogrel and aspirin are presenting for non-elective surgery. No consensus on the timing of surgery exists after withdrawal of antiplatelet and tests of platelet function are not routinely available. The Thrombelastography Platelet Mapping (TEG-PM) assay is designed to assess platelet inhibition secondary to antiplatelet therapy. We assessed its ability to detect platelet inhibition in preoperative acute surgical patients. METHODS: We conducted a prospective observational study in three groups of preoperative patients: those taking clopidogrel or aspirin up to admission, and a control group. TEG-PM was performed on the day of admission and alternate days until surgery. RESULTS: Mean (SD) platelet thromboxane A(2) receptor inhibition in the control group was 17.5% (23.8) (n=20), 52.6% (32.3) (n=18) in the aspirin group, and 31.9% (27.6) (n=21) in the clopidogrel group (P<0.01). Mean (SD) platelet adenosine diphosphate (ADP) receptor inhibition in the control group was 47.8% (18.9) (n=20), 52.6% (19.7) (n=18) in the aspirin group, and 71.5% (18.4) (n=21) in the clopidogrel group (P<0.01). Among the clopidogrel group awaiting surgery, mean platelet ADP channel inhibition decreased on day 3 to 67.1% (24.7) (n=11), 48.8% (24.4) (n=4) on day 5, and 36.1% (15.9) (n=2) on day 7 (P=0.57). CONCLUSIONS: TEG-PM can identify statistically significant platelet inhibition after antiplatelet therapy; however, the overlap in platelet receptor inhibition between the three groups is likely to limit the clinical usefulness of this test.

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OBJECTIVES: To examine the influence that the provision of environmental information might be able to make on personal travel behaviour through analysis of the views of members of the public expressed in a study for the UK Department for Transport on attitudes towards carbon calculator tools. STUDY DESIGN: A three-stage qualitative survey taking an ideographic approach to analysing public attitudes to the use of carbon calculator tools in relation to making transport decisions. METHODS: Interviews and discussion groups with stakeholders, non-users and users providing extensive data that were analysed using the British Market Research Bureau's matrix mapping methodology. RESULTS: Despite considerable awareness of climate change as an issue, personal carbon emissions were not found to have much influence on personal transport choice, which could be seen as being dominated by issues of cost (both in time and money), comfort and convenience. CONCLUSIONS: The spatial and temporal dislocation of the cause and effects of climate change make it difficult to link the impacts of personal travel behaviour with specific activities. If environmental- and health-based information is to be provided as a lever to change travel behaviour, it may be necessary to provide information on issues such as local air pollution and personal health impacts in order to link wider benefits with a travel user's self-interest.

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BACKGROUND: The Counterweight Programme provides an evidence based and effective approach for weight management in routine primary care. Uptake of the programme has been variable for practices and patients. Aim. To explore key barriers and facilitators of practice and patient engagement in the Counterweight Programme and to describe key strategies used to address barriers in the wider implementation of this weight management programme in UK primary care. METHODS: All seven weight management advisers participated in a focus group. In-depth interviews were conducted with purposeful samples of GPs (n = 7) and practice nurses (n = 15) from 11 practices out of the 65 participating in the programme. A total of 37 patients participated through a mixture of in-depth interviews (n = 18) and three focus groups. Interviews and focus groups were analysed for key themes that emerged. RESULTS: Engagement of practice staff was influenced by clinicians' beliefs and attitudes, factors relating to the way the programme was initiated and implemented, the programme content and organizational/contextual factors. Patient engagement was influenced by practice endorsement of the programme, clear understanding of programme goals, structured proactive follow-up and perception of positive outcomes. CONCLUSIONS: Having a clear understanding of programme goals and expectations, enhancing self-efficacy in weight management and providing proactive follow-up is important for engaging both practices and patients. The widespread integration of weight management programmes into routine primary care is likely to require supportive public policy.

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