The forced adoption of a fast-track appraisal process for a breast cancer treatment in UK

Trastuzumab (Herceptin ®, Roche) is approved in UK for the treatment of the metastatic breast cancer since 2001. As of 2005, concomitantly with the publication of 3 studies that showed it produces a 50% reduction of the recurrence rates of breast cancer, trastuzumab started to be prescribed in the earlt adjuvant treatrnent of this disease. Und June 2006, trastuzumab did not have both: 1) regulatory approval and 2) NICE [National Institute for Health and Clinical Excellence] recommendation for the use in early stages of breast cancer. During the period until June 2006, the trastuzumab use in those patients was not reimbursed and because the cost of trastuzumab is equal with the yearly UK average income, most of patients could not self fund their treatrnent. Before the publication of the final NICE guidance, the new data of trastuzumab in early breast cancer raised enormous patient and professional interest and expectations. A great volume of public and professional pressure was generated to transcend a system by which Primary Care Trusts can reimburse a treatment only after a formal guidance was issued. This paper draw on a case study depicting and analyzing the process by which regulatory approval and NICE recommendations were achieved in a record time and how trastuzumab became a standard treatment on early adjuvant breast cancer. According to the data we gathered in this work we were witnessing one of the fastest processes of adoption of a health care technology since the creation of NICE, in 1999. This study addresses the following research question: How and why does the adoption pattern of trastuzumab differ from the rational decision-making model of the reimbursement process in UK? [Author, p. 4]

Modern statistical models for forensic fingerprint examinations : a critical review

Over the last decade, the development of statistical models in support of forensic fingerprint identification has been the subject of increasing research attention, spurned on recently by commentators who claim that the scientific basis for fingerprint identification has not been adequately demonstrated. Such models are increasingly seen as useful tools in support of the fingerprint identification process within or in addition to the ACE-V framework. This paper provides a critical review of recent statistical models from both a practical and theoretical perspective. This includes analysis of models of two different methodologies: Probability of Random Correspondence (PRC) models that focus on calculating probabilities of the occurrence of fingerprint configurations for a given population, and Likelihood Ratio (LR) models which use analysis of corresponding features of fingerprints to derive a likelihood value representing the evidential weighting for a potential source.

A 2D/3D image analysis system to track fluorescently labeled structures in rod-shaped cells: application to measure spindle pole asymmetry during mitosis.

BACKGROUND: The yeast Schizosaccharomyces pombe is frequently used as a model for studying the cell cycle. The cells are rod-shaped and divide by medial fission. The process of cell division, or cytokinesis, is controlled by a network of signaling proteins called the Septation Initiation Network (SIN); SIN proteins associate with the SPBs during nuclear division (mitosis). Some SIN proteins associate with both SPBs early in mitosis, and then display strongly asymmetric signal intensity at the SPBs in late mitosis, just before cytokinesis. This asymmetry is thought to be important for correct regulation of SIN signaling, and coordination of cytokinesis and mitosis. In order to study the dynamics of organelles or large protein complexes such as the spindle pole body (SPB), which have been labeled with a fluorescent protein tag in living cells, a number of the image analysis problems must be solved; the cell outline must be detected automatically, and the position and signal intensity associated with the structures of interest within the cell must be determined. RESULTS: We present a new 2D and 3D image analysis system that permits versatile and robust analysis of motile, fluorescently labeled structures in rod-shaped cells. We have designed an image analysis system that we have implemented as a user-friendly software package allowing the fast and robust image-analysis of large numbers of rod-shaped cells. We have developed new robust algorithms, which we combined with existing methodologies to facilitate fast and accurate analysis. Our software permits the detection and segmentation of rod-shaped cells in either static or dynamic (i.e. time lapse) multi-channel images. It enables tracking of two structures (for example SPBs) in two different image channels. For 2D or 3D static images, the locations of the structures are identified, and then intensity values are extracted together with several quantitative parameters, such as length, width, cell orientation, background fluorescence and the distance between the structures of interest. Furthermore, two kinds of kymographs of the tracked structures can be established, one representing the migration with respect to their relative position, the other representing their individual trajectories inside the cell. This software package, called "RodCellJ", allowed us to analyze a large number of S. pombe cells to understand the rules that govern SIN protein asymmetry. CONCLUSIONS: "RodCell" is freely available to the community as a package of several ImageJ plugins to simultaneously analyze the behavior of a large number of rod-shaped cells in an extensive manner. The integration of different image-processing techniques in a single package, as well as the development of novel algorithms does not only allow to speed up the analysis with respect to the usage of existing tools, but also accounts for higher accuracy. Its utility was demonstrated on both 2D and 3D static and dynamic images to study the septation initiation network of the yeast Schizosaccharomyces pombe. More generally, it can be used in any kind of biological context where fluorescent-protein labeled structures need to be analyzed in rod-shaped cells. AVAILABILITY: RodCellJ is freely available under http://bigwww.epfl.ch/algorithms.html, (after acceptance of the publication).

How useful is satellite positioning system (GPS) to track gait parameters? A review.

Over the last century, numerous techniques have been developed to analyze the movement of humans while walking and running. The combined use of kinematics and kinetics methods, mainly based on high speed video analysis and forceplate, have permitted a comprehensive description of locomotion process in terms of energetics and biomechanics. While the different phases of a single gait cycle are well understood, there is an increasing interest to know how the neuro-motor system controls gait form stride to stride. Indeed, it was observed that neurodegenerative diseases and aging could impact gait stability and gait parameters steadiness. From both clinical and fundamental research perspectives, there is therefore a need to develop techniques to accurately track gait parameters stride-by-stride over a long period with minimal constraints to patients. In this context, high accuracy satellite positioning can provide an alternative tool to monitor outdoor walking. Indeed, the high-end GPS receivers provide centimeter accuracy positioning with 5-20 Hz sampling rate: this allows the stride-by-stride assessment of a number of basic gait parameters--such as walking speed, step length and step frequency--that can be tracked over several thousand consecutive strides in free-living conditions. Furthermore, long-range correlations and fractal-like pattern was observed in those time series. As compared to other classical methods, GPS seems a promising technology in the field of gait variability analysis. However, relative high complexity and expensiveness--combined with a usability which requires further improvement--remain obstacles to the full development of the GPS technology in human applications.

Binge eating in binge eating disorder: a break-down of emotion regulatory process?

Current explanatory models for binge eating in binge eating disorder (BED) mostly rely onmodels for bulimianervosa (BN), although research indicates different antecedents for binge eating in BED. This studyinvestigates antecedents and maintaining factors in terms of positive mood, negative mood and tension in asample of 22 women with BED using ecological momentary assessment over a 1-week. Values for negativemood were higher and those for positive mood lower during binge days compared with non-binge days.During binge days, negative mood and tension both strongly and significantly increased and positive moodstrongly and significantly decreased at the first binge episode, followed by a slight though significant, andlonger lasting decrease (negative mood, tension) or increase (positive mood) during a 4-h observation periodfollowing binge eating. Binge eating in BED seems to be triggered by an immediate breakdown of emotionregulation. There are no indications of an accumulation of negative mood triggering binge eating followed byimmediate reinforcing mechanisms in terms of substantial and stable improvement of mood as observed inBN. These differences implicate a further specification of etiological models and could serve as a basis fordeveloping new treatment approaches for BED.

Streamlining the medication process improves safety in the intensive care unit.

BACKGROUND: Multiple interventions were made to optimize the medication process in our intensive care unit (ICU). 1 Transcriptions from the medical order form to the administration plan were eliminated by merging both into a single document; 2 the new form was built in a logical sequence and was highly structured to promote completeness and standardization of information; 3 frequently used drug names, approved units, and fixed routes were pre-printed; 4 physicians and nurses were trained with regard to the correct use of the new form. This study was aimed at evaluating the impact of these interventions on clinically significant types of medication errors. METHODS: Eight types of medication errors were measured by a prospective chart review before and after the interventions in the ICU of a public tertiary care hospital. We used an interrupted time-series design to control the secular trends. RESULTS: Over 85 days, 9298 lines of drug prescription and/or administration to 294 patients, corresponding to 754 patient-days were collected and analysed for the three series before and three series following the intervention. Global error rate decreased from 4.95 to 2.14% (-56.8%, P < 0.001). CONCLUSIONS: The safety of the medication process in our ICU was improved by simple and inexpensive interventions. In addition to the optimization of the prescription writing process, the documentation of intravenous preparation, and the scheduling of administration, the elimination of the transcription in combination with the training of users contributed to reducing errors and carried an interesting potential to increase safety.

New perspectives in the use of ink evidence in forensic science: Part I. Development of a quality assurance process for forensic ink analysis by HPTLC

The level of information provided by ink evidence to the criminal and civil justice system is limited. The limitations arise from the weakness of the interpretative framework currently used, as proposed in the ASTM 1422-05 and 1789-04 on ink analysis. It is proposed to use the likelihood ratio from the Bayes theorem to interpret ink evidence. Unfortunately, when considering the analytical practices, as defined in the ASTM standards on ink analysis, it appears that current ink analytical practices do not allow for the level of reproducibility and accuracy required by a probabilistic framework. Such framework relies on the evaluation of the statistics of the ink characteristics using an ink reference database and the objective measurement of similarities between ink samples. A complete research programme was designed to (a) develop a standard methodology for analysing ink samples in a more reproducible way, (b) comparing automatically and objectively ink samples and (c) evaluate the proposed methodology in a forensic context. This report focuses on the first of the three stages. A calibration process, based on a standard dye ladder, is proposed to improve the reproducibility of ink analysis by HPTLC, when these inks are analysed at different times and/or by different examiners. The impact of this process on the variability between the repetitive analyses of ink samples in various conditions is studied. The results show significant improvements in the reproducibility of ink analysis compared to traditional calibration methods.

New roles for community pharmacists in modern health care systems: a challenge for pharmacy education and research.

The academic activities led by the Unit of Community Pharmacy can be classified as translational. Our group is interested in person-centered pharmaceutical services aimed at a more responsible use of drugs (effectiveness, safety, efficiency) in collaboration with physicians and other health care professionals in a primary care setting. The following domains of education and research are high priorities for our group: medication therapy management, medication adherence, integrated care, individualization of therapies, care management for the elderly and e-health.

Cerebrospinal fluid antimicroglial antibodies in Alzheimer disease: a putative marker of an ongoing inflammatory process.

Immunocompetent microglia play an important role in the pathogenesis of Alzheimer's disease (AD). Antimicroglial antibodies in the cerebrospinal fluid (CSF) in clinically diagnosed AD patients have been previously recorded. Here, we report the results of the analysis of the CSF from 38 autopsy cases: 7 with definite AD; 14 with mild and 10 with moderate Alzheimer's type pathology; and 7 controls. Antimicroglial antibodies were identified in 70% of patients with definite AD, in 80% of patients with moderate and in 28% of patients with mild Alzheimer's type pathology. CSF antimicroglial antibodies were not observed in any of the control cases. The results show that CSF antimicroglial antibodies are present in the majority of patients with definite AD and also in cases with moderate Alzheimer's type changes. They may also indicate dysregulation of microglial function. Together with previous observations, these findings indicate that compromised immune defense mechanisms play an important role in the pathogenesis of AD.

Reforms of the pre-graduate curriculum for medical students: the Bologna process and beyond.

For several years, all five medical faculties of Switzerland have embarked on a reform of their training curricula for two reasons: first, according to a new federal act issued in 2006 by the administration of the confederation, faculties needed to meet international standards in terms of content and pedagogic approaches; second, all Swiss universities and thus all medical faculties had to adapt the structure of their curriculum to the frame and principles which govern the Bologna process. This process is the result of the Bologna Declaration of June 1999 which proposes and requires a series of reforms to make European Higher Education more compatible and comparable, more competitive and more attractive for Europeans students. The present paper reviews some of the results achieved in the field, focusing on several issues such as the shortage of physicians and primary care practitioners, the importance of public health, community medicine and medical humanities, and the implementation of new training approaches including e-learning and simulation. In the future, faculties should work on several specific challenges such as: students' mobility, the improvement of students' autonomy and critical thinking as well as their generic and specific skills and finally a reflection on how to improve the attractiveness of the academic career, for physicians of both sexes.