A comparison of methods for treatment selection in seamless phase II/III clinical trials incorporating information on short-term endpoints

In an adaptive seamless phase II/III clinical trial interim analysis data are used for treatment selection, enabling resources to be focussed on comparison of more effective treatment(s) with a control. In this paper we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focusses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short-term and long-term endpoints

Time Since Last Dental Clinic Visit and Self-Reported Health among the Elderly

Background. This study determined the association between time since last dental clinic visit and self-reported health among the elderly (age ≥ 65 years). Methods. Data were from the 2010 Behavioral Risk Factor Surveillance System. A logistic regression analysis was conducted to identify factors that affect the self-reported general health of the elderly. Additionally, a negative binomial regression analysis was conducted to explore the association of time since last dental clinic visit and the self-reported number of physically unhealthy, mentally unhealthy, and sad days during the past 30 days. Results. Six predictors were identified affecting the self-reported general health of the elderly. Respondents were more likely to self-report “good, very good, or excellent” general health if they: visited the dental clinic within the past year, were non-Hispanic, had healthcare coverage, had fewer permanent teeth removed, received better education and were younger. A larger lapse of time since respondents’ last dental clinic visits was associated with increased number of mentally and physically unhealthy days and an increased number of sad days during the past 30 days. Conclusions. The positive association between better general health, fewer mentally and physically unhealthy days, and fewer sad days during the past 30 days and shorter periods of time between dental visits warrants further investigation to determine a possible causal relationship between overall health and dental visits

Student family housing at Kansas State University: satisfaction and future programs

Call number: LD2668 .T4 1979 S26Master of Scienc

Adaptive clinical trials incorporating treatment selection and evaluation: methodology and application in progressive multiple sclerosis

In progressive multiple sclerosis (MS) irreversible disability often takes many years to accumulate as a result prolonged trials are required to assess the benefits of therapies. There is a need to understand the relationship between short-term outcome measures such as MRI endpoints and long-term clinical outcomes in progression to determine the evolution of the disease early on. Thus, the common phase I-II-III paradigm for clinical trial design with separate trials for each phase may not be appropriate

Do Childhood Cancer Survivors Meet the Diet and Physical Activity Guidelines? A Review of Guidelines and Literature

Despite advances in cancer treatment, childhood cancer survivors are at higher risk of developing chronic health conditions than peers who do not have cancer. Being overweight or obese adds to the already elevated risk of cardiovascular diseases and metabolic abnormalities that childhood cancer survivors experience. Diet and physical activity are modifiable behaviors that reduce obesity risk and have been shown to improve cancer survival in adult cancer survivors. Specific guidelines have been developed for cancer survivors that provide advice on nutrition, physical activity and weight management following cancer diagnosis and treatment. In this review, we report on existing nutrition and physical activity guidelines for cancer survivors, supplemented by available literature on diet and physical activity status of childhood cancer survivors and their associations with health-related outcomes. The 2012 American Cancer Society (ACS) and the 2008 Children's Oncology Group (COG) guidelines provide similar advice on diet but the ACS guidelines also offer specific advice on physical activity and weight management.  Thirty-one observational studies and 18 intervention trials published prior to June 2012 that met the inclusion criteria were reviewed. Results suggest that a high proportion of childhood cancer survivors had poor adherence to dietary and physical activity guidelines. Although findings from existing intervention trials are preliminary due to small sample size, available evidence suggests that exercise intervention is safe and feasible for patients and survivors of childhood cancer. Childhood cancer survivors should be encouraged to engage in physical activity, adopt a healthful diet, and maintain a healthy weight throughout cancer survivorship. (word count: 250

Sub-diffraction error mapping for localisation microscopy images

Assessing the quality of localisation microscopy images is highly challenging due to the difficulty in reliably detecting errors in experimental data. The most common failure modes are the biases and errors produced by the localisation algorithm when there is emitter overlap. Also known as the high density or crowded field condition, significant emitter overlap is normally unavoidable in live cell imaging. Here we use Haar wavelet kernel analysis (HAWK), a localisation microscopy data analysis method which is known to produce results without bias, to generate a reference image. This enables mapping and quantification of reconstruction bias and artefacts common in all but low emitter density data. By avoiding comparisons involving intensity information, we can map structural artefacts in a way that is not adversely influenced by nonlinearity in the localisation algorithm. The HAWK Method for the Assessment of Nanoscopy (HAWKMAN) is a general approach which allows for the reliability of localisation information to be assessed

A Methodology for Appropriate Testing When Data is Heterogeneous Using EXCEL

A Methodology for Appropriate Testing When Data is Heterogeneous was originally published and copy written in the mid-1990s in Turbo Pascal and a 16-bit operating system.  While working on an ergonomic dissertation (Yearout, 1987), the author determined that the perceptual lighting preference data was heterogeneous and not normal.  Drs. Milliken and Johnson, the authors of Analysis of Messy Data Volume I: Designed Experiments (1989), advised that Satterthwaite’s Approximation with Bonferroni’s Adjustment to correct for pairwise error be used to analyze the heterogeneous data. This technique of applying linear combinations with adjusted degrees of freedom allowed the use of t-Table criteria to make group comparisons without using standard nonparametric techniques.  Thus data with unequal variances and unequal sample sizes could be analyzed without losing valuable information.  Variances to the 4th power were so large that they could not be reentered into basic calculators.  The solution was to develop an original software package which was written in Turbo Pascal on a 7 ¼ inch disk 16-bit operating system.  Current operating systems of 32 and 64 bits and more efficient programming languages have made the software obsolete and unusable. Using the old system could result either in many returns being incorrect or the system terminating.  The purpose of this research was to develop a spreadsheet algorithm with multiple interactive EXCEL worksheets that will efficiently apply Satterthwaite’s Approximation with Bonferroni’s Adjustment to solve the messy data problem.  To ensure that the pedagogy is accurate, the resulting package was successfully tested in the classroom with academically diverse students.  A comparison between this technique and EXCEL’s Add-Ins Analysis ToolPak for a t-test Two-Sample Assuming Unequal Variances was conducted using several different data sets.  The results of this comparison were that the EXCEL Add-Ins returned incorrect significant differences.  Engineers, ergonomists, psychologists, and social scientists will find the developed program very useful. A major benefit is that spreadsheets will continue to be current regardless of evolving operating systems’ status

How do hospital professionals involved in a randomised controlled trial perceive the value of genotyping vs. PCR-ribotyping for control of hospital acquired C. difficile infections?

Background: Despite scientific advances in typing of C. difficile strains very little is known about how hospital staff use typing results during periods of increased incidence (PIIs). This qualitative study, undertaken alongside a randomised controlled trial (RCT), explored this issue. The trial compared ribotyping versus more rapid genotyping (MLVA or multilocus variable repeat analysis) and found no significant difference in post 48 hour cases (C difficile transmissions). Methods: In-depth qualitative interviews with senior staff in 11/16 hospital trusts in the trial (5 MLVA and 6 Ribotyping). Semi-structured interviews were conducted at end of the trial period. Transcripts were content analysed using framework analysis supported by NVivo-8 software. Common sub-themes were extracted by two researchers independently. These were compared and organised into over-arching categories or ‘super-ordinate themes’. Results: The trial recorded that 45% of typing tests had some impact on infection control (IC) activities. Interviews indicated that tests had little impact on initial IC decisions. These were driven by hospital protocols and automatically triggered when a PII was identified. To influence decision-making, a laboratory turnaround time < 3 days (ideally 24 hours) was suggested; MLVA turnaround time was 5.3 days. Typing results were predominantly used to modify initiated IC activities such as ward cleaning, audits of practice or staff training; major decisions (e.g. ward closure) were unaffected. Organisational factors could limit utilisation of MLVA results. Results were twice as likely to be reported as ‘aiding management’ (indirect benefit) than impacting on IC activities (direct effect). Some interviewees considered test results provided reassurance about earlier IC decisions; others identified secondary benefits on organisational culture. An underlying benefit of improved discrimination provided by MLVA typing was the ability to explore epidemiology associated with CDI cases in a hospital more thoroughly. Conclusions: Ribotyping and MLVA are both valued by users. MLVA had little additional direct impact on initial infection control decisions. This would require reduced turnaround time. The major impact is adjustments to earlier IC measures and retrospective reassurance. For this, turnaround time is less important than discriminatory power. The potential remains for wider use of genotyping to examine transmission routes

Simulating tidal and storm surge hydraulics with a simple 2D inertia based model, in the Humber Estuary, U.K

The hydraulic modelling of tidal estuarine environments has been largely limited to complex 3D models that are computationally expensive. This makes them unsuitable for applications which make use of live data to make real/near time forecasts, such as the modelling of storm surge propagation and associated flood inundation risks. To address this requirement for a computationally efficient method a reduced complexity, depth-integrated 2D storage cell model (Lisflood-FP) has been applied to the Humber Estuary, UK. The capability of Lisflood-FP to reproduce the tidal heights of the Humber Estuary has been shown by comparing modelled and observed tidal stage heights over a period of a week. The feasibility of using the Lisflood-FP model to forecast flood inundation risk from a storm surge is demonstrated by reproducing the major storm surge that struck the UK East Coast and Humber Estuary on 5 December 2013. Results show that even for this 2013 extreme event the model is capable of reproducing the hydraulics and tidal levels of the estuary. Using present day flood defences and observed flooding extents, the modelled flood inundation areas produced by the model were compared, showing agreement in most areas and illustrating the model's potential as a now-casting early warning system when driven by publically available data, and in near real-time. The Lisflood-FP model used was incorporated into the CAESAR-Lisflood GUI, with the calibration and verification of the estuarine hydraulics reported herein being a key step in creating an estuary evolution model, capable of operating in the decadal to century timescales that are presently underrepresented in estuarine predictive capability, and ultimately developing a model to predict the evolution of flood risk over the longer term