A questionnaire elicitation of surgeons' belief about learning within a surgical trial

PMID: 23145113 [PubMed - indexed for MEDLINE] PMCID: PMC3493499 Free PMC ArticlePeer reviewedPublisher PD

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

A systematic review of the use of an expertise-based randomised controlled trial design

Acknowledgements JAC held a Medical Research Council UK methodology (G1002292) fellowship, which supported this research. The Health Services Research Unit, Institute of Applied Health Sciences (University of Aberdeen), is core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Views express are those of the authors and do not necessarily reflect the views of the funders.Peer reviewedPublisher PD

Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines

Background: Multiple imputation (MI) provides an effective approach to handle missing covariate data within prognostic modelling studies, as it can properly account for the missing data uncertainty. The multiply imputed datasets are each analysed using standard prognostic modelling techniques to obtain the estimates of interest. The estimates from each imputed dataset are then combined into one overall estimate and variance, incorporating both the within and between imputation variability. Rubin's rules for combining these multiply imputed estimates are based on asymptotic theory. The resulting combined estimates may be more accurate if the posterior distribution of the population parameter of interest is better approximated by the normal distribution. However, the normality assumption may not be appropriate for all the parameters of interest when analysing prognostic modelling studies, such as predicted survival probabilities and model performance measures. Methods: Guidelines for combining the estimates of interest when analysing prognostic modelling studies are provided. A literature review is performed to identify current practice for combining such estimates in prognostic modelling studies. Results: Methods for combining all reported estimates after MI were not well reported in the current literature. Rubin's rules without applying any transformations were the standard approach used, when any method was stated. Conclusion: The proposed simple guidelines for combining estimates after MI may lead to a wider and more appropriate use of MI in future prognostic modelling studies

REporting recommendations for tumour MARKer prognostic studies (REMARK)

Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. Similar to the successful CONSORT initiative for randomised trials and the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Conservative management of a grade V injury to an ectopic pelvic kidney following blunt trauma to the lower abdomen: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ectopic pelvic kidneys represent an anatomic variant that remains clinically asymptomatic in most patients. While there is some literature to suggest that ectopic kidneys may be more predisposed to blunt trauma injuries, there are few examples to guide the management of these injuries. To our knowledge, we present the first case of a grade V renal injury to an ectopic pelvic kidney managed successfully with conservative measures.</p> <p>Case Presentation</p> <p>We present a case of grade V renal injury to an ectopic pelvic kidney in a 21 year-old African-American male. The clinical and radiographic findings are presented, along with the patient's conservative hospital course.</p> <p>Conclusion</p> <p>We suggest that management of grade V renal injuries to ectopic pelvic kidneys can be treated similarly to that of kidneys in normal anatomic position. Conservative measures may be considered in properly selected patients.</p

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

A pilot telephone intervention to increase uptake of breast cancer screening in socially deprived areas in Scotland (TELBRECS):study protocol for a randomised controlled trial

BACKGROUND Breast cancer accounts for almost 30% of all cancers and is the second leading cause of cancer deaths in women in Scotland. Screening is key to early detection. The Scottish Breast Screening Programme is a nationwide, free at point of delivery screening service, to which all women aged between 50 and 70 years are invited to attend every 3 years. Currently over three-quarters of invited women regularly attend screening. However, women from more deprived areas are much less likely to attend: for example in the 3 years from 2010-2012 only 63% of women in the most deprived area attended the East of Scotland Breast Screening programme versus 81% in the least deprived. Research has suggested that reminders (telephone or letter) and brief, personalised interventions addressing barriers to attendance may be helpful in increasing uptake in low-income women. METHODS/DESIGN We will employ a brief telephone reminder and support intervention, whose purpose is to elicit and address any mistaken beliefs women have about breast screening, with the aim that the perceived benefits of screening come to outweigh any perceived barriers for individuals. We will test whether this intervention, plus a simple anticipated regret manipulation, will lead to an increase in the uptake of breast cancer screening amongst low-income women who have failed to attend a first appointment, in a randomised controlled trial with 600 women. Participants will be randomly allocated to one of four treatment arms i.e. 1) Letter reminder (i.e. Treatment as usual: CONTROL); 2) Telephone reminder (TEL), 3) Telephone reminder plus telephone support (TEL-SUPP) and 4) Telephone reminder plus support plus AR (TEL-SUPP-AR). The primary outcome will be attendance at breast screening within 3 months of the reminder letter. DISCUSSION If this simple telephone support intervention (with or without AR intervention) leads to a significant increase in breast screening attendance, this would represent a rare example of a theoretically-driven, relatively simple psychological intervention that could result in earlier detection of breast cancer amongst an under-served group of lower socio-economic women. TRIAL REGISTRATION Current Controlled trials: ISRCTN06039270. Registered 16th January 2014

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen