Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis

Study aim: The aim of this study was to characterise adherence in an adult population with CF and to investigate if variation in lung function was a predictor of adherence to treatment. Patients and methods: Patients aged ≥ 16 years from an adult CF centre undertook adherence measures by medication possession ratio (MPR) and self-report and were assigned to one of three adherence categories (<50%, 50-<80%, 80% and above) by their composite score (MPR). Ordinal regression was used to identify predictors of adherence including coefficient variation measures for forced expiratory volume in 1 second (FEV1), weight and C-reactive protein, measured up to 6 and 12 months. Results: MPR data for 106 of 249 patients [mean age 29.8 (±9.2) years] was retrieved, indicating a mean adherence of 63%. Coefficient of variation FEV1 was inversely related to adherence and was a univariate predictor of adherence (6 months: 0.92 [0.87-0.98] p= 0.005 and 12 months: 0.94 [0.93-0.99], p=0.03]) and remained significant in the final models. The coefficient variation of weight and C-reactive protein were not predictive of adherence. Conclusions: Coefficient of variation FEV1 was identified as an objective predictor of adherence. Further evaluation of this potential marker of adherence is now required

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Supercritical water oxidation of dioxins and furans in waste incinerator fly ash, sewage sludge and industrial soil

Three environmental samples containing dioxins and furans have been oxidized in the presence of hydrogen peroxide under supercritical water oxidation conditions. The samples consisted of a waste incinerator fly ash, sewage sludge and contaminated industrial soil. The reactor system was a batch, autoclave reactor operated at temperatures between 350°C and 450°C, corresponding to pressures of ~20-33.5 MPa and with hydrogen peroxide concentrations from 0.0 to 11.25 vol%. Hydrogen peroxide concentration and temperature/pressure had a strong positive effect on the oxidation of dioxins and furans. At the highest temperatures and pressure of supercritical water oxidation of 450°C and 33.5 MPa and with 11.25 vol% of hydrogen peroxide, the destruction efficiencies of the individual polychlorinated dibenzo-ρ-dioxins/polychlorinated dibenzofurans (PCDD/PCDF) isomers were between 90% and 99%. There did not appear to be any significant differences in the PCDD/PCDF destruction efficiencies in relation to the different sample matrices of the waste incinerator fly ash, sewage sludge and contaminated industrial soil

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

Do you think it's a disease? a survey of medical students

Background: The management of medical conditions is influenced by whether clinicians regard them as "disease" or "not a disease". The aim of the survey was to determine how medical students classify a range of conditions they might encounter in their professional lives and whether a different name for a condition would influence their decision in the categorisation of the condition as a 'disease' or 'not a disease'. Methods. We surveyed 3 concurrent years of medical students to classify 36 candidate conditions into "disease" and "non-disease". The conditions were given a 'medical' label and a (lay) label and positioned where possible in alternate columns of the survey. Results: The response rate was 96% (183 of 190 students attending a lecture): 80% of students concurred on 16 conditions as "disease" (eg diabetes, tuberculosis), and 4 as "non- disease" (eg baldness, menopause, fractured skull and heat stroke). The remaining 16 conditions (with 21-79% agreement) were more contentious (especially obesity, infertility, hay fever, alcoholism, and restless leg syndrome). Three pairs of conditions had both a more, and a less, medical label: the more medical labels (myalgic encephalomyelitis, hypertension, and erectile dysfunction) were more frequently classified as 'disease' than the less medical (chronic fatigue syndrome, high blood pressure, and impotence), respectively, significantly different for the first two pairs. Conclusions: Some conditions excluded from the classification of "disease" were unexpected (eg fractured skull and heat stroke). Students were mostly concordant on what conditions should be classified as "disease". They were more likely to classify synonyms as 'disease' if the label was medical. The findings indicate there is still a problem 30 years on in the concept of 'what is a disease'. Our findings suggest that we should be addressing such concepts to medical students

CUSUM: A tool for early feedback about performance?

BACKGROUND: Modern day clinical practice demands evidence justifying our choice of treatment methods. Cumulative sum techniques (cusum) are amongst the simplest statistical methods known. They provide rapid analysis and identification of trends in a series of data. This study highlights use of these techniques as an early performance indicator of a clinical procedure before its implementation. METHODS: Twenty consecutive patients who underwent total hip or knee arthroplasty received a simple dressing – blue gauze and Tegaderm. Cusum charting was used to assess the dressing with regards to skin blistering. At an acceptable level of performance the curve would oscillate about the horizontal axis and the overall trend therefore said to be flat. If performance is unacceptable, the cusum slopes upward. RESULTS: The cusum plot for the twenty patients did not cross the specified control limits. This showed that our simple dressing met specified standards with regards to wound blistering postoperatively. CONCLUSION: We recommend the use of this simple, yet versatile cusum technique in the early evaluation of a clinical procedure before its implementation