An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Evaluation of major feed resources in crop-livestock mixed farming systems, southern Ethiopia: Indigenous knowledge versus laboratory analysis results

Evaluation of major feed resources was conducted in four crop-livestock mixed farming systems of central southern Ethiopia, with 90 farmers, selected using multi-stage purposive and random sampling methods. Discussions were held with focused groups and key informants for vernacular name identification of feed, followed by feed sampling to analyse chemical composition (CP, ADF and NDF), in-vitro dry matter digestibility (IVDMD), and correlate with indigenous technical knowledge (ITK). Native pastures, crop residues (CR) and multi-purpose trees (MPT) are the major feed resources, demonstrated great variations in seasonality, chemical composition and IVDMD. The average CP, NDF and IVDMD values for grasses were 83.8 (ranged: 62.9–190), 619 (ranged: 357–877) and 572 (ranged: 317–743) g kg^(−1) DM, respectively. Likewise, the average CP, NDF and IVDMD for CR were 58 (ranged: 20–90), 760 (ranged: 340–931) and 461 (ranged: 285–637)g kg^(−1) DM, respectively. Generally, the MPT and non-conventional feeds (NCF, Ensete ventricosum and Ipomoea batatas) possessed higher CP (ranged: 155–164 g kg^(−1) DM) and IVDMD values (611–657 g kg^(−1) DM) while lower NDF (331–387 g kg^(−1) DM) and ADF (321–344 g kg^(−1) DM) values. The MPT and NCF were ranked as the best nutritious feeds by ITK while crop residues were the least. This study indicates that there are remarkable variations within and among forage resources in terms of chemical composition. There were also complementarities between ITK and feed laboratory results, and thus the ITK need to be taken into consideration in evaluation of local feed resources.

Compositional ideas in the bayesian analysis of categorical data with application to dose finding clinical trials

Compositional random vectors are fundamental tools in the Bayesian analysis of categorical data. Many of the issues that are discussed with reference to the statistical analysis of compositional data have a natural counterpart in the construction of a Bayesian statistical model for categorical data. This note builds on the idea of cross-fertilization of the two areas recommended by Aitchison (1986) in his seminal book on compositional data. Particular emphasis is put on the problem of what parameterization to use

Medical Evaluation Processes in Clinical settings. Qualitative Analysis through the Experience of Teachers and Studens

Evaluation processes in clinical practice have not been well, being their study focused on the technical issues concerning these processes. This study tried an approach to the evaluation processes through the analysis of perceptions from teachers and students about the methodology of evaluation considering the teachinglearning processes performed in a clinical practice of the Medicine Program –Universidad El Bosque from Bogota. With this purpose we conducted interviews with teachers and students searching the manner in which the evaluative, learning and teaching processes are done; then we analyzed the perception from both agents concerning the way these processes are related. The interviews were categorized bath deductively and inductively, and then contrasted with some current theories of learning, teaching and evaluation in medicine. The study showed that nowadays the evaluation and, in general, the educative processes are affected by several factors which are associated to the manner the professional practice is developed, and the educative process of the current teachers. We concluded there is no congrency between the approach of the evaluation, mainly conductivist, and the learning and teaching strategies mainly constructivist. This fact cause dissent in teachers and students.

Multidisciplinary analysis of clinical cases: a transition towards active learning in dental education

In the past 2009/10 academic year, we took steps towards introduction of active methodologies, from a multidisciplinar approach, into a conventional lecture-based Dental Education program. We consolidated these practices in the current 2010/11 year, already within a new Bologna-adapted scheme. Transition involved (i) critical assessment of the limitations of traditional teaching (ii) identification of specific learning topics allowing for integration of contents, (iii) implementation of student-centred learning activities in old curricular plans (iv) assessment of students' satisfaction and perceived learning outcomes, (v) implementation of these changes in new Bologna-adapted curricula

Diagnostic analysis of atmospheric moisture and clear-sky radiative feedback in the Hadley Centre and Geophysical Fluid Dynamics Laboratory (GFDL) climate models

The interannual variability of the hydrological cycle is diagnosed from the Hadley Centre and Geophysical Fluid Dynamics Laboratory (GFDL) climate models, both of which are forced by observed sea surface temperatures. The models produce a similar sensitivity of clear-sky outgoing longwave radiation to surface temperature of ∼2 W m−2 K−1, indicating a consistent and positive clear-sky radiative feedback. However, differences between changes in the temperature lapse-rate and the height dependence of moisture fluctuations suggest that contrasting mechanisms bring about this result. The GFDL model appears to give a weaker water vapor feedback (i.e., changes in specific humidity). This is counteracted by a smaller upper tropospheric temperature response to surface warming, which implies a compensating positive lapse-rate feedback.

A comparison of three different models for estimating relative risk in meta-analysis of clinical trials under unobserved heterogeneity

We focus on the comparison of three statistical models used to estimate the treatment effect in metaanalysis when individually pooled data are available. The models are two conventional models, namely a multi-level and a model based upon an approximate likelihood, and a newly developed model, the profile likelihood model which might be viewed as an extension of the Mantel-Haenszel approach. To exemplify these methods, we use results from a meta-analysis of 22 trials to prevent respiratory tract infections. We show that by using the multi-level approach, in the case of baseline heterogeneity, the number of clusters or components is considerably over-estimated. The approximate and profile likelihood method showed nearly the same pattern for the treatment effect distribution. To provide more evidence two simulation studies are accomplished. The profile likelihood can be considered as a clear alternative to the approximate likelihood model. In the case of strong baseline heterogeneity, the profile likelihood method shows superior behaviour when compared with the multi-level model. Copyright (C) 2006 John Wiley & Sons, Ltd.

Genomic analysis of recombinant Sabin clinical isolates

Recombination in Poliovirus vaccine strains is a very frequent phenomenon. In this report 23 polio/Sabin strains isolated from healthy vaccinees or from VAPP patients after OPV administration, were investigated in order to identify recombination sites from 2C to 3D regions of the poliovirus genome. RT-PCR, followed by Restriction Fragment Length Polymorphism (RFLP) screening analysis were applied in four distant genomic regions (5' UTR, VP1, 2C and 3C-3D) in order to detect any putative recombinant. The detected recombinants were sequenced from 2C to the end of the genome (3' UTR) and the exact recombination sites were determined with computational analysis. Five of the 23 isolated strains were recombinant in one genomic region, two of them in 2C, isolates EP16:S3/S2, EP23:S3/S1, two in 3D isolates EP6:S2/S1, EP12:S2/S1 and one in 3A isolate EP9:S2/Sl. Point mutations were found in strains EP3, EP6, EP9 and EP12. Recombination specific types and sites re-occurrence along with point mutations are discussed concerning the polioviruses evolution.

Validating a new clinical subtyping scheme for delirium with electronic motion analysis

The usefulness of motor subtypes of delirium is unclear due to inconsistency in sub-typing methods and a lack of validation with objective measures of activity. The activity of 40 patients was measured with 24 h accelerometry monitoring. Patients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) delirium (n = 30) were allocated into hyperactive, hypoactive and mixed motor subtypes. Delirium subtypes differed in relation to overall amount of activity, including movement in both sagittal and transverse planes. Differences were greater in the daytime and during the early evening ‘sundowning’ period. Frequency of postural changes was the most discriminating measure examined. Clinical subtypes of delirium defined by observed motor behaviour on the ward differ in electronically measured activity levels.

Are clinical documents optimised for patient safety? A critical analysis of patient safety outcomes using the EDA error model

Iatrogenic errors and patient safety in clinical processes are an increasing concern. The quality of process information in hardcopy or electronic form can heavily influence clinical behaviour and decision making errors. Little work has been undertaken to assess the safety impact of clinical process planning documents guiding the clinical actions and decisions. This paper investigates the clinical process documents used in elective surgery and their impact on latent and active clinical errors. Eight clinicians from a large health trust underwent extensive semi- structured interviews to understand their use of clinical documents, and their perceived impact on errors and patient safety. Samples of the key types of document used were analysed. Theories of latent organisational and active errors from the literature were combined with the EDA semiotics model of behaviour and decision making to propose the EDA Error Model. This model enabled us to identify perceptual, evaluation, knowledge and action error types and approaches to reducing their causes. The EDA error model was then used to analyse sample documents and identify error sources and controls. Types of knowledge artefact structures used in the documents were identified and assessed in terms of safety impact. This approach was combined with analysis of the questionnaire findings using existing error knowledge from the literature. The results identified a number of document and knowledge artefact issues that give rise to latent and active errors and also issues concerning medical culture and teamwork together with recommendations for further work.

Use of nutritional complete supplements in older adults with dementia: systematic review and meta-analysis of clinical outcomes

Background & Aims: Malnutrition is prevalent in people diagnosed with dementia however ensuring adequate oral intake within this group is often problematic. It is important to determine whether providing nutritionally complete oral nutritional supplements (ONS) drinks is an effective way of improving clinical outcomes for older people with dementia. This paper systematically reviewed clinical, wellbeing and nutritional outcomes in people with long-term cognitive impairment. Methods: The CINAHL, Medline and EMBASE databases were searched from their inception until January 2012. Reference lists of the included papers, foreign language papers and review articles obtained were manually searched. Results: Twelve articles were included in the review containing 1076 people in the supplement groups (intervention) and 748 people in the control groups. Meta-analysis shows there was a significant improvement in weight (p=<0.0001), Body Mass Index (BMI) (p=<0.0001) and cognition at 6.5+/-3.9 month follow up (p=0.002) when supplements were given compared to the control group. Conclusions: Providing ONS drinks has a positive effect on weight gain and cognition at follow up in older people with dementia. Additional research is required in both comparing nutritional supplements to vitamin/mineral tablets and high protein/calorie shots and clinical outcomes relevant to hospitalised people with dementia.

Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials

There is an urgent need to treat individuals with high blood pressure (BP) with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP) ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT). Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was −2.95 mmHg (95% CI: −4.17, −1.73; p < 0.001), and for DBP was −1.51 mmHg (95% CI: −2.21, −0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP). Both publication bias and “small-study effect” were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.