Barriers and facilitators to attendance at Type 2 diabetes structured education programmes: a qualitative study of educators and attendees.

AIMS: Attendance at structured diabetes education has been recommended internationally for all people with Type 2 diabetes. However, attendance rates are consistently low. This qualitative study aimed to explore experiences of attending and delivering Type 2 diabetes structured education programmes in Ireland and barriers and facilitators to attendance. METHODS: People with Type 2 diabetes who had attended one of the three programmes delivered in Ireland and educators from the three programmes took part in semi-structured telephone interviews. Interviews were audio-taped, transcribed and analysed using inductive thematic analysis. RESULTS: Twelve attendees and 14 educators were interviewed. Two themes were identified in relation to experiences of programme attendance and delivery: 'Structured education: addressing an unmet need' and 'The problem of non-attendance'. The third theme 'Barriers to attendance: can't go, won't go, don't know and poor system flow' outlined how practicalities of attending, lack of knowledge of the existence and benefits, and limited resources and support for education within the diabetes care pathway impacts on attendance. The final theme 'Supporting attendance: healthcare professionals and the diabetes care pathway' describes facilitators to participants' attendance and the strategies educators perceived to be important in increasing attendance. CONCLUSIONS: Healthcare professionals have an important role in improving attendance at structured diabetes education programmes. Improving attendance may require promotion by healthcare professionals and for education to be better embedded and supported within the diabetes care pathway.

The preferences of young adults with Type 1 diabetes at clinics using a discrete choice experiment approach: the D1 Now Study.

AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.

Factors influencing health-related quality of life in patients with Type 1 diabetes.

AIMS: Generic, preference-based measures of health-related quality of life (HRQoL) are a common input to the economic evaluation of new health technologies. As such, it is important to explore what characteristics of patients with Type 1 diabetes might impact scores on such measures. METHODS: This study utilizes baseline data from a cluster-randomized trial that recruited patients with Type 1 diabetes at six centers across Ireland. Health-related quality of life was assessed using the three-level EuroQol EQ-5D (EQ-5D) measure. Patients' responses to individual dimensions of the EQ-5D were explored. To see which patient factors influenced EQ-5D scores, multivariate regression analysis was conducted with EQ-5D scores as the outcome variable. RESULTS: Data was available for 437 Type 1 diabetes patients. The median age of these patients was 40 (IQR: 31-49) years and 53.8% were female. Overall, patients reported a high HRQoL based on EQ-5D scores (0.87 (SD: 0.19). Fifty-four percent of patients reported a perfect HRQoL. For those that reported problems, the most common dimension was the anxiety/depression dimension of the EQ-5D (29.6%). In the multivariate regression analysis, self-reported mental illness (- 0.22 (95% CI: -0.34, - 0.10)) and being unemployed (- 0.07 (95% CI: -0.13, - 0.02)) were negatively associated with EQ-5D scores (p < 0.05). The influence of self-reported mental illness was persistent in sensitivity analyses. CONCLUSIONS: The study results indicate that patients with Type 1 diabetes report a high HRQoL based on responses to the EQ-5D. However, there are a substantial number of Type 1 diabetes patients that report problems in the anxiety/depression dimension, which may provide avenues to improve patients' HRQoL. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79759174 .

The Perceptions of Patients, their Parents and Healthcare Providers on the Transition of Young Adults with Type 1 Diabetes to Adult Services in the West of Ireland.

Aim This study aims to describe the perceptions of young adults', parents of young adults' and health care professionals' (HCPs) of the transition process for young adults with Type 1 Diabetes in the West of Ireland. Methods Thematic analysis of semi-structured interviews conducted with the three stakeholder groups was performed. Results Young adults hardly noticed the transition, with many of them seeing it as a physical move, whereas parents were more anxious and felt their involvement was still needed but not accommodated. Both groups perceived the young adults' ability to manage their diabetes as a facilitator, as well as the continuity of care provided by the diabetes nurse. Resource limitations and an inability of a young adult to self-manage were identified as barriers to smooth transition by parents, whilst HCPs were experiencing problems with non-attendance and a lack of a psychology service. Conclusion This study highlights the importance of encouraging adolescents' autonomy in the years leading to transition. A key healthcare professional link between both services appears to facilitate smooth transition. Being flexible and supportive of both parents and adolescents including the provision of mental health services are other important considerations.

The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

BACKGROUND: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. METHOD: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

A systematic review of interventions to improve outcomes for young adults with Type 1 diabetes.

BACKGROUND: Many young adults with Type 1 diabetes experience poor outcomes. The aim of this systematic review was to synthesize the evidence regarding the effectiveness of interventions aimed at improving clinical, behavioural or psychosocial outcomes for young adults with Type 1 diabetes. METHODS: Electronic databases were searched. Any intervention studies related to education, support, behaviour change or health service organizational change for young adults aged between 15-30 years with Type 1 diabetes were included. A narrative synthesis of all studies was undertaken due to the large degree of heterogeneity between studies. RESULTS: Eighteen studies (of a possible 1700) were selected and categorized: Health Services Delivery (n = 4), Group Education and Peer Support (n = 6), Digital Platforms (n = 4) and Diabetes Devices (n = 4). Study designs included one randomized controlled trial, three retrospective studies, seven feasibility/acceptability studies and eight studies with a pre/post design. Continuity, support, education and tailoring of interventions to young adults were the most common themes across studies. HbA1c was the most frequently measured outcome, but only 5 of 12 studies that measured it showed a significant improvement. CONCLUSION: Based on the heterogeneity among the studies, the effectiveness of interventions on clinical, behavioural and psychosocial outcomes among young adults is inconclusive. This review has highlighted a lack of high-quality, well-designed interventions, aimed at improving health outcomes for young adults with Type 1 diabetes.

Multilocus DNA sequencing of the whiskey fungus reveals a continental-scale speciation pattern.

Baudoinia was described to accommodate a single species, B. compniacensis. Known as the 'whiskey fungus', this species is the predominant member of a ubiquitous microbial community known colloquially as 'warehouse staining' that develops on outdoor surfaces subject to periodic exposure to ethanolic vapours near distilleries and bakeries. Here we examine 19 strains recovered from environmental samples near industrial settings in North America, South America, the Caribbean, Europe and the Far East. Molecular phylogenetic analysis of a portion of the nucLSU rRNA gene confirms that Baudoinia is a monophyletic lineage within the Teratosphaeriaceae (Capnodiales). Multilocus phylogenetic analysis of nucITS rRNA (ITS1-5.8S-ITS2) and partial nucLSU rRNA, beta-tubulin (TUB) and elongation factor 1-alpha (TEF1) gene sequences further indicates that Baudoinia consists of five strongly supported, geographically patterned lineages representing four new species (viz. Baudoinia antilliensis, B. caledoniensis, B. orientalis and B. panamericana).

Temporal change in the gut community of rats fed high amylose cornstarch is driven by endogenous urea rather than strictly on carbohydrate availability.

AIM: To examine change in the gut community of rats fed high amylose maize starch (HAMS). METHODS AND RESULTS: Rats were fed AIN93G diets containing HAMS (5% resistant starch type 2) or alphacell (control). HAMS increased faecal short-chain fatty acid output, faecal propionate and total bacteria output but reduced gut pH and blood urea concentrations compared with rats ingesting the control diet. Feeding HAMS resulted in a gut community dominated by four phylotypes homologous with Ruminococcus bromii, Bacteroides uniformis and with yet to be cultivated organisms aligning into the Family Porphyromonadaceae. Enrichment of phylotypes aligning within the Bacteroidetes occurred primarily in the caecum, whereas those homologous with R. bromii were found primarily in the faeces. HAMS altered community structure such that the phylum Bacteroidetes represented the dominant gut lineage and progressively reduced faecal community phylotype richness over the duration of feeding. CONCLUSIONS: Feeding HAMS resulted in a caecal and faecal community dominated by organisms that require ammonia as a primary nitrogen source. Gut ammonia derived from endogenous urea represents an important factor contributing to caecal community composition in addition to the ability to utilize HAMS. Increases in faecal propionate, rather than butyrate as is often observed following resistant starch feeding, reflected a gut community dominated by the Bacteroidetes. SIGNIFICANCE: Diet-mediated change is often viewed strictly in terms of available carbohydrate. Here, we have shown that ammonia derived from endogenous urea is an important factor contributing to gut community composition and structure in rats fed this substrate.

Perceptions of anonymised data use and awareness of the NHS data opt-out amongst patients, carers and healthcare staff.

BACKGROUND: England operates a National Data Opt-Out (NDOO) for the secondary use of confidential health data for research and planning. We hypothesised that public awareness and support for the secondary use of health data and the NDOO would vary by participant demography and healthcare experience. We explored patient/public awareness and perceptions of secondary data use, grouping potential researchers into National Health Service (NHS), academia or commercial. We assessed awareness of the NDOO system amongst patients, carers, healthcare staff and the public. We co-developed recommendations to consider when sharing unconsented health data for research. METHODS: A patient and public engagement program, co-created and including patient and public workshops, questionnaires and discussion groups regarding anonymised health data use. RESULTS: There were 350 participants in total. Central concerns for health data use included unauthorised data re-use, the potential for discrimination and data sharing without patient benefit. 94% of respondents were happy for their data to be used for NHS research, 85% for academic research and 68% by health companies, but less than 50% for non-healthcare companies and opinions varied with demography and participant group. Questionnaires showed that knowledge of the NDOO was low, with 32% of all respondents, 53% of all NHS staff and 29% of all patients aware of the NDOO. Recommendations to guide unconsented secondary health data use included that health data use should benefit patients; data sharing decisions should involve patients/public. That data should remain in close proximity to health services with the principles of data minimisation applied. Further, that there should be transparency in secondary health data use, including publicly available lists of projects, summaries and benefits. Finally, organisations involved in data access decisions should participate in programmes to increase knowledge of the NDOO, to ensure public members were making informed choices about their own data. CONCLUSION: The majority of participants in this study reported that the use of healthcare data for secondary purposes was acceptable when accessed by NHS. Academic and health-focused companies. However, awareness was limited, including of the NDOO. Further development of publicly-agreed recommendations for secondary health data use may improve both awareness and confidence in secondary health data use.

Health data from routine care can be pseudonymised (with a link remaining to the patient but identifying features removed) or anonymised (with identifying features removed and the link to the patient severed) and used for research and health planning; termed "secondary use". The National Health Service (NHS) is a single publicly-funded health service for the United Kingdom (UK). The NHS supports secondary data use with a National Data opt-out system. The potential benefits of data secondary use are clear but concerns have been raised. Although the Data Opt-Out is publicised, it is unclear how much public awareness there is of this scheme. We report a patient and publicly created and delivered series of activities including > 350 people; with young adults, patients, NHS staff and the public; to assess concerns, knowledge and acceptance of data sharing.Perceptions of and support for secondary health data use varied depending on who was asked (by age, gender) and their experience of health services (Staff member, patient, member of the public). Knowledge of schemes to limit secondary data use (such as the UK National Data Op-Out) was low, even among NHS staff. The main concerns of sharing health data included onward data use, the potential for discrimination and exploitation and commercial gain from data use with no benefit to patients. Despite this, most participants agreed with health data sharing with NHS, academic and commercial health-based entities. Agreed, co-created themes to increase the acceptability of health data secondary use included education about 'Opt-out' schemes, health service oversight of data use (as the most trusted partner), public and patient involvement in data sharing decisions and public transparency.

The association between prepregnancy obesity and screening positive for postpartum depression.

OBJECTIVE: To describe the association between reported prepregnancy body mass index (BMI) and screening positive for depression. DESIGN: Cohort study. SETTING: Four urban hospitals in Utah, USA. POPULATION: Women delivering a term, singleton, live-born infant at one of four urban hospitals in Utah in the period 2005-2007. METHODS: Women were enrolled immediately postpartum. Demographic, anthropometric, stressors, psychiatric, and medical/obstetric and family-history data were obtained. Prepregnancy height, weight, and pregnancy weight gain were self-reported. The primary exposure variable, prepregnancy BMI, was calculated. Women were stratified into the six World Health Organization BMI categories (underweight, normal weight, pre-obese, or obese class 1-3). MAIN OUTCOME MEASURE: At 6-8 weeks postpartum, women were screened for depression using the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome measure was a prespecified EPDS score of > or =12. RESULTS: Among the 1053 women studied, 14.4% of normal weight women screened positive for postpartum depression. This proportion was greater in women classed as underweight (18.0%, n = 11), pre-obese (18.5%, n = 38), obese class 1 (18.8%, n = 16), obese class 2 (32.4%, n = 11), and obese class 3 (40.0%, n = 8) (P < 0.01). Controlling for demographic, psychological, and medical/obstetric factors, prepregnancy class-2 (aOR 2.87, 95% CI 1.21-6.81) and class-3 (aOR 3.94, 95% CI 1.38-11.23) obesity remained strongly associated with screening positive for postpartum depression, compared with women of normal weight. CONCLUSIONS: Self-reported prepregnancy obesity may be associated with screening positive for depression when measured postpartum.

Experimental petrology of lunar material: the nature of mascons, seas, and the lunar interior.

One-atmosphere melting data show that Apollo 11 samples are near cotectic. Melting relations at pressures up to 35 kilobars show that clinopyroxenite or amphibole peridotite are possible lunar interiors. Mascons cannot be eclogite; they may be ilmenite accumulate. Hot lunar surface material will boil off alkalis.

Development of a protocol to measure volatile organic compounds in human breath: a comparison of rebreathing and on-line single exhalations using proton transfer reaction mass spectrometry.

Analysis of volatile organic compounds (VOCs) on human breath has great potential as a non-invasive diagnostic technique. It is, therefore, surprising that no single, standard procedure has evolved for breath sampling. Here we present a novel repeated-cycle isothermal rebreathing method, where one cycle comprises five rebreaths, which could be adopted for breath analysis of VOCs. For demonstration purposes, we present measurements of three common breath VOCs: isoprene, acetone and methanol. Their concentrations measured in breath are shown to increase with number of rebreaths until a plateau value is reached by at least 20 rebreaths. The average ratio of plateau concentration to single mixed expired breath concentration was found to be 1.92 +/- 0.57 for isoprene, 1.25 +/- 0.13 for acetone and 1.12 +/- 0.12 for methanol (mean +/- standard deviation). Measurements from on-line single exhalations are presented which demonstrate a positive slope in the time-dependent expirograms of isoprene and acetone. The slope of the isoprene expirogram is persistently linear and the end-expired concentration of isoprene is highly variable in the same subject depending on the duration of exhalation. End-expired values of acetone are not as sensitive to the length of exhalation, and are the same to within measurement uncertainty for any duration of exhalation for any subject. It is concluded that uncontrolled single on-line exhalations are not suitable for the reliable measurement of isoprene in the breath and that rebreathing can be the basis of an easily tolerated protocol for the reliable collection of breath samples.

Tool making cockatoos adjust the lengths but not the widths of their tools to function.

The ability to innovatively use or even manufacture different tools depending on a current situation can be silhouetted against examples of stereotyped, inborn tool use/manufacture and is thus often associated to advanced cognitive processing. In this study we confronted non-specialized, yet innovative tool making birds, Goffin's cockatoos (Cacatua goffiniana), with an apparatus featuring an out-of-reach food reward that could be placed at different distances from a tool opening. Alternatively, the food stayed at a constant distance but the tool opening in the front of the apparatus had different diameters. We used a novel material for tool manufacture (cardboard) that demanded an incrementally increased manufacturing effort from the actor, depending on the length of the tool required. We found that our subjects used two strategies to succeed in this tasks: either by making carboard-stripe tools using the full length of the material sheets originally offered or by adjusting the lengths of their tools to different goal distances. Subjects also discarded cardboard stripes that were too short to reach the goal prior to use and discarded longer pieces when the goal was further away than when it was close. Nevertheless, likely due to morphological constraints, the birds failed to adjust the widths of their tools depending on the diameter of the tool opening.

An optimized work-flow to reduce time-to-detection of carbapenemase-producing Enterobacteriaceae (CPE) using direct testing from rectal swabs.

Rapid detection of patients with carbapenemase-producing Enterobacteriaceae (CPE) is essential for the prevention of nosocomial cross-transmission, allocation of isolation facilities and to protect patient safety. Here, we aimed to design a new laboratory work-flow, utilizing existing laboratory resources, in order to reduce time-to-diagnosis of CPE. A review of the current CPE testing processes and of the literature was performed to identify a real-time commercial polymerase chain reaction (PCR) assay that could facilitate batch testing of CPE clinical specimens, with adequate CPE gene coverage. Stool specimens (210) were collected; CPE-positive inpatients (n = 10) and anonymized community stool specimens (n = 200). Rectal swabs (eSwab™) were inoculated from collected stool specimens and a manual DNA extraction method (QIAamp® DNA Stool Mini Kit) was employed. Extracted DNA was then processed on the Check-Direct CPE® assay. The three step process of making the eSwab™, extracting DNA manually and running the Check-Direct CPE® assay, took <5 min, 1 h 30 min and 1 h 50 min, respectively. It was time efficient with a result available in under 4 h, comparing favourably with the existing method of CPE screening; average time-to-diagnosis of 48/72 h. Utilizing this CPE work-flow would allow a 'same-day' result. Antimicrobial susceptibility testing results, as is current practice, would remain a 'next-day' result. In conclusion, the Check-Direct CPE® assay was easily integrated into a local laboratory work-flow and could facilitate a large volume of CPE screening specimens in a single batch, making it cost-effective and convenient for daily CPE testing.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

Elimination characteristics of post-operative isoflurane levels in alveolar exhaled breath via PTR-MS analysis.

Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), C3H2ClF5O, is a commonly used inhalation anaesthetic. Using a proton transfer reaction mass spectrometer (PTR-MS) we have detected isoflurane in the breath of patients several weeks following major surgery. That isoflurane is detected in the breath of patients so long after being anaesthetised raises questions about when cognitive function has fully returned to a patient. Temporal profiles of isoflurane concentrations in breath are presented for five patients (F/M 3/2, mean age 50 years, min-max 36-58 years) who had undergone liver transplant surgery. In addition, results from a headspace analysis of isoflurane are presented so that the product ions resulting from the reactions of H3O+ with isoflurane in PTR-MS could be easily identified in the absence of the complex chemical environment of breath. Six product ions were identified. In order of increasing m/z (using the 35Cl isotope where appropriate) these are [Formula: see text] (m/z 51), CHFCl+ (m/z 67), CF3CHCl+ (m/z 117), C3F4OCl+ (m/z 163), C3H2F4OCl+ (m/z 165), and C3F4OCl+ H2O (m/z 183). No protonated parent was detected. For the headspace study both clean air and CO2 enriched clean air (4% CO2) were used as buffer gases in the drift tube of the PTR-MS. The CO2 enriched air was used to determine if exhaled breath would affect the product ion branching ratios. Importantly no significant differences were observed, and therefore for isoflurane the product ion distributions determined in a normal air mixture can be used for breath analysis. Given that PTR-MS can be operated under different reduced electric fields (E/N), the dependence of the product ion branching percentages for isoflurane on E/N (96-138 Td) are reported.

Nintendo Wii Fit as an adjunct to physiotherapy following lower limb fractures: preliminary feasibility, safety and sample size considerations.

OBJECTIVE: The Nintendo Wii Fit integrates virtual gaming with body movement, and may be suitable as an adjunct to conventional physiotherapy following lower limb fractures. This study examined the feasibility and safety of using the Wii Fit as an adjunct to outpatient physiotherapy following lower limb fractures, and reports sample size considerations for an appropriately powered randomised trial. METHODOLOGY: Ambulatory patients receiving physiotherapy following a lower limb fracture participated in this study (n=18). All participants received usual care (individual physiotherapy). The first nine participants also used the Wii Fit under the supervision of their treating clinician as an adjunct to usual care. Adverse events, fracture malunion or exacerbation of symptoms were recorded. Pain, balance and patient-reported function were assessed at baseline and discharge from physiotherapy. RESULTS: No adverse events were attributed to either the usual care physiotherapy or Wii Fit intervention for any patient. Overall, 15 (83%) participants completed both assessments and interventions as scheduled. For 80% power in a clinical trial, the number of complete datasets required in each group to detect a small, medium or large effect of the Wii Fit at a post-intervention assessment was calculated at 175, 63 and 25, respectively. CONCLUSIONS: The Nintendo Wii Fit was safe and feasible as an adjunct to ambulatory physiotherapy in this sample. When considering a likely small effect size and the 17% dropout rate observed in this study, 211 participants would be required in each clinical trial group. A larger effect size or multiple repeated measures design would require fewer participants.

Limonene in exhaled breath is elevated in hepatic encephalopathy.

Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol-1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol-1, respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10-44) and 42 (32-58) nmol mol-1.

Synergy between a human c-myc transgene and p53 null genotype in murine thymic lymphomas: contrasting effects of homozygous and heterozygous p53 loss.

Activation of the c-myc oncogene and functional loss of the p53 tumour suppressor gene are among the most frequently recorded genetic lesions in neoplasia but their combined effect has not previously been investigated. By breeding together mice transgenic for human c-myc (CD2-myc) and mice carrying an inactive p53 allele (p53-/-) we found that these genetic lesions act synergistically in vivo. Offspring carrying the CD2-myc transgene and the homozygous p53 null mutation (p53-/-/CD2-myc) were viable but developed thymic lymphomas with dramatically increased frequency and reduced latency compared to both parental groups. The tumour phenotype was similar to that previously recorded for CD2-myc mice (predominantly CD3+, CD4+8+) but tumour clonal complexity and metastasis was significantly greater in the p53-/-/CD2-myc mice. In contrast, no significant increase in tumour incidence was seen in p53+/-/CD2-myc vs p53+/+/CD2-myc mice over a 6 month observation period. However, the loss of wild type p53 in a proportion of tumour cells in p53+/-/CD2-myc lymphomas suggests that wild type allele loss can occur as a late progression step rather than an initiating step in these tumours. We suggest that p53 loss of function may collaborate with the CD2-myc transgene at more than one stage in thymic lymphoma development.