Continuous monitoring and feedback of quality of recovery indicators for anaesthetists: a qualitative investigation of reported effects on professional behaviour

Background Research suggests that providing clinicians with feedback on their performance can result in professional behaviour change and improved clinical outcomes. Departments would benefit from understanding which characteristics of feedback support effective quality monitoring, professional behaviour change and service improvement. This study aimed to report the experience of anaesthetists participating in a long-term initiative to provide comprehensive personalized feedback to consultants on patient-reported quality of recovery indicators in a large London teaching hospital. Methods Semi-structured interviews were conducted with 13 consultant anaesthetists, six surgical nursing leads, the theatre manager and the clinical coordinator for recovery. Transcripts were qualitatively analysed for themes linked to the perceived value of the initiative, its acceptability and its effects upon professional practice. Results Analysis of qualitative data from participant interviews suggested that effective quality indicators must address areas that are within the control of the anaesthetist. Graphical data presentation, both longitudinal (personal variation over time) and comparative (peer-group distributions), was found to be preferable to summary statistics and provided useful and complementary perspectives for improvement. Developing trust in the reliability and credibility of the data through co-development of data reports with clinical input into areas such as case-mix adjustment was important for engagement. Making feedback specifically relevant to the recipient supported professional learning within a supportive and open collaborative environment. Conclusions This study investigated the requirements for effective feedback on quality of anaesthetic care for anaesthetists, highlighting the mechanisms by which feedback may translate into improvements in practice at the individual and peer-group level

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt

Hdac6 Knock-Out Increases Tubulin Acetylation but Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease

Huntington's disease (HD) is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC) inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6) in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF) from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD

Hdac6 Knock-Out Increases Tubulin Acetylation but Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease

Huntington's disease (HD) is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC) inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6) in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF) from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD

Infant growth disparity in the Khanh Hoa province in Vietnam: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Surveys in Vietnam have indicated that wasting and stunting have been prevalent among children, but the country is undergoing rapid socio-economic changes and little has been known about the relative situation in the different areas of the country. In 2006, the WHO introduced new growth standards applicable to all infant and child populations, which facilitates for improved assessments of the prevalence of growth impairment, independent of time, place and ethnicity. The aim of our study was to assess the growth of singleton infants delivered at term in three main birth clinics in the Khanh Hoa province in Vietnam by using the new WHO standards as reference, and the association between growth and some maternal, birth and health factors.</p> <p>Methods</p> <p>A cohort of 237 singleton infants born in the period May-July 2005 in three main delivery clinics in the Khanh Hoa province were observed prospectively. Their anthropometrical measures a year later were compared to the WHO sex-specific growth standards for weight-for-age, length-for-age, weight-for-length, and BMI-for-age. These measures were analysed as dependent outcomes using multiple linear regression models including the following independent factors: urban vs. rural birth, 1-minute Apgar score, weight and length at birth, duration of lactation, ever had diarrhoea, dengue fever, pneumonia or dysentery, and maternal age, height, gestational duration and parity.</p> <p>Results</p> <p>Compared to the standard distributions, 79% were below the median for weight-for-length; 18.0% were within the 5^thpercentile for length-for-age, 9.6% for weight-for-age, 20.3% for weight-for-length, and 19.8% for BMI. A lower length- and weight-for-age were statistically associated with being born rurally.</p> <p>Conclusions</p> <p>In this delivery-clinic based sample of children in the Khanh Hoa province in Vietnam, the proportions within the WHO-standard 5^thpercentiles for length-for-age, weight-for-length and BMI in late infancy were 3-4 times higher than expected, which indicate that deficient growth is prevalent. The infants born in a rural area had a lower weight- and length-for-age than their urban counterparts, independent of diarrhoea.</p

Mouse DRG Cell Line with Properties of Nociceptors

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons

New Zealand Blackcurrant Extract Improves Cycling Performance and Fat Oxidation in Cyclists

PURPOSE: Blackcurrant intake increases peripheral blood flow in humans, potentially by anthocyanin-induced vasodilation which may affect substrate delivery and exercise performance. We examined the effects of New Zealand blackcurrant (NZBC) extract on substrate oxidation, cycling time-trial performance and plasma lactate responses following the time-trial in trained cyclists. METHODS: Using a randomized, double-blind, crossover design, fourteen healthy men (age: 38 ± 13 years, height: 178 ± 4 cm, body mass: 77 ± 9 kg, V?O2max: 53 ± 6 ml·kg-1·min-1, mean ± SD) ingested NZBC extract (300 mg?day-1 CurraNZ™ containing 105 mg anthocyanin) or placebo (PL, 300 mg microcrystalline cellulose M102) for 7-days (washout 14-days). On day 7, participants performed 30 min of cycling (3x10 min at 45, 55 and 65% V?O2max), followed by a 16.1 km time-trial with lactate sampling during a 20-minute passive recovery. RESULTS: NZBC extract increased fat oxidation at 65% V?O2max by 27% (P < 0.05) and improved 16.1 km time-trial performance by 2.4% (NZBC: 1678 ± 108 s, PL: 1722 ± 131 s, P < 0.05). Plasma lactate was higher with NZBC extract immediately following the time-trial (NZBC: 7.06 ± 1.73 mmol?L-1, PL: 5.92 ± 1.58 mmol?L-1 P < 0.01). CONCLUSIONS: Seven days intake of New Zealand blackcurrant extract improves 16.1 km cycling time-trial performance and increases fat oxidation during moderate intensity cycling