Test result-based sampling: an efficient design for estimating the accuracy of patient safety indicators.

OBJECTIVE: Accuracy studies of Patient Safety Indicators (PSIs) are critical but limited by the large samples required due to low occurrence of most events. We tested a sampling design based on test results (verification-biased sampling [VBS]) that minimizes the number of subjects to be verified. METHODS: We considered 3 real PSIs, whose rates were calculated using 3 years of discharge data from a university hospital and a hypothetical screen of very rare events. Sample size estimates, based on the expected sensitivity and precision, were compared across 4 study designs: random and VBS, with and without constraints on the size of the population to be screened. RESULTS: Over sensitivities ranging from 0.3 to 0.7 and PSI prevalence levels ranging from 0.02 to 0.2, the optimal VBS strategy makes it possible to reduce sample size by up to 60% in comparison with simple random sampling. For PSI prevalence levels below 1%, the minimal sample size required was still over 5000. CONCLUSIONS: Verification-biased sampling permits substantial savings in the required sample size for PSI validation studies. However, sample sizes still need to be very large for many of the rarer PSIs.

Field testing of arsenic in groundwater samples of Bangladesh using a test kit based on lyophilized bioreporter bacteria.

A test kit based on living, lyophilized bacterial bioreporters emitting bioluminescence as a response to arsenite and arsenate was applied during a field campaign in six villages across Bangladesh. Bioreporter field measurements of arsenic in groundwater from tube wells were in satisfying agreement with the results of spectroscopic analyses of the same samples conducted in the lab. The practicability of the bioreporter test in terms of logistics and material requirements, suitability for high sample throughput, and waste disposal was much better than that of two commercial chemical test kits that were included as references. The campaigns furthermore demonstrated large local heterogeneity of arsenic in groundwater, underscoring the use of well switching as an effective remedy to avoid high arsenic exposure.

COLOX: a new blood-based test for colorectal cancer screening

INTRODUCTION/OBJECTIVES: Detection rates for adenoma and early colorectal cancer (CRC) are insufficient due to low compliance towards invasive screening procedures, like colonoscopy.Available non-invasive screening tests have unfortunately low sensitivity and specificity performances.Therefore, there is a large unmet need calling for a cost-effective, reliable and non-invasive test to screen for early neoplastic and pre-neoplastic lesions AIMS & Methods: The objective is to develop a screening test able to detect early CRCs and adenomas.This test is based on a nucleic acids multi-gene assay performed on peripheral blood mononuclear cells (PBMCs).A colonoscopy-controlled feasibility study was conducted on 179 subjects.The first 92 subjects was used as training set to generate a statistical significant signature.Colonoscopy revealed 21 subjects with CRC,30 with adenoma bigger than 1 cm and 41 with no neoplastic or inflammatory lesions.The second group of 48 subjects (controls, CRC and polyps) was used as a test set and will be kept blinded for the entire data analysis.To determine the organ and disease specificity 38 subjects were used:24 with inflammatory bowel disease (IBD),14 with other cancers than CRC (OC).Blood samples were taken from each patient the day of the colonoscopy and PBMCs were purified. Total RNA was extracted following standard procedures.Multiplex RT-qPCR was applied on 92 different candidate biomarkers.Different univariate and multivariate statistical methods were applied on these candidates and among them 60 biomarkers with significant p-values (<0.01) were selected.These biomarkers are involved in several different biological functions as cellular movement,cell signaling and interaction,tissue and cellular development,cancer and cell growth and proliferation.Two distinct biomarker signatures are used to separate patients without lesion from those with cancer or with adenoma, named COLOX CRC and COLOX POL respectively.COLOX performances were validated using random resampling method, bootstrap. RESULTS: COLOX CRC and POL tests successfully separate patients without lesions from those with CRC (Se 67%,Sp 93%,AUC 0.87) and from those with adenoma bigger than 1cm (Se 63%,Sp 83%,AUC 0.77),respectively. 6/24 patients in the IBD group and 1/14 patients in the OC group have a positive COLOX CRC CONCLUSION: The two COLOX tests demonstrated a high sensitivity and specificity to detect the presence of CRCs and adenomas bigger than 1 cm.A prospective, multicenter, pivotal study is underway in order to confirm these promising results in a larger cohort.

Evaluation of an online, case-based interactive approach to teaching pathophysiology

AIM: The aim of this study was to evaluate a new pedagogical approach in teaching fluid, electrolyte and acid-base pathophysiology in undergraduate students. METHODS: This approach comprises traditional lectures, the study of clinical cases on the web and a final interactive discussion of these cases in the classroom. When on the web, the students are asked to select laboratory tests that seem most appropriate to understand the pathophysiological condition underlying the clinical case. The percentage of students having chosen a given test is made available to the teacher who uses it in an interactive session to stimulate discussion with the whole class of students. The same teacher used the same case studies during 2 consecutive years during the third year of the curriculum. RESULTS: The majority of students answered the questions on the web as requested and evaluated positively their experience with this form of teaching and learning. CONCLUSIONS: Complementing traditional lectures with online case-based studies and interactive group discussions represents, therefore, a simple means to promote the learning and the understanding of complex pathophysiological mechanisms. This simple problem-based approach to teaching and learning may be implemented to cover all fields of medicine.

Influence of a lifestyle intervention in preschool children on physiological and psychological parameters (Ballabeina): study design of a cluster randomized controlled trial.

Childhood obesity and physical inactivity are increasing dramatically worldwide. Children of low socioeconomic status and/or children of migrant background are especially at risk. In general, the overall effectiveness of school-based programs on health-related outcomes has been disappointing. A special gap exists for younger children and in high risk groups. This paper describes the rationale, design, curriculum, and evaluation of a multicenter preschool randomized intervention study conducted in areas with a high migrant population in two out of 26 Swiss cantons. Twenty preschool classes in the German (canton St. Gallen) and another 20 in the French (canton Vaud) part of Switzerland were separately selected and randomized to an intervention and a control arm by the use of opaque envelopes. The multidisciplinary lifestyle intervention aimed to increase physical activity and sleep duration, to reinforce healthy nutrition and eating behaviour, and to reduce media use. According to the ecological model, it included children, their parents and the teachers. The regular teachers performed the majority of the intervention and were supported by a local health promoter. The intervention included physical activity lessons, adaptation of the built infrastructure; promotion of regional extracurricular physical activity; playful lessons about nutrition, media use and sleep, funny homework cards and information materials for teachers and parents. It lasted one school year. Baseline and post-intervention evaluations were performed in both arms. Primary outcome measures included BMI and aerobic fitness (20 m shuttle run test). Secondary outcomes included total (skinfolds, bioelectrical impedance) and central (waist circumference) body fat, motor abilities (obstacle course, static and dynamic balance), physical activity and sleep duration (accelerometry and questionnaires), nutritional behaviour and food intake, media use, quality of life and signs of hyperactivity (questionnaires), attention and spatial working memory ability (two validated tests). Researchers were blinded to group allocation. The purpose of this paper is to outline the design of a school-based multicenter cluster randomized, controlled trial aiming to reduce body mass index and to increase aerobic fitness in preschool children in culturally different parts of Switzerland with a high migrant population. Trial Registration: (clinicaltrials.gov) NCT00674544.

Teaching evidence-based management with a focus on producing local evidence

We present an approach to teaching evidence-based management (EBMgt) that trains future managers how to produce local evidence. Local evidence is causally interpretable data, collected on-site in companies to address a specific business problem. Our teaching method is a variant of problem-based learning, a method originally developed to teach evidence-based medicine. Following this method, students learn an evidence-based problem-solving cycle for addressing actual business cases. Executing this cycle, students use and produce scientific evidence through literature searches and the design of local, experimental tests of causal hypotheses. We argue the value of teaching EBMgt with a focus on producing local evidence, how it can be taught, and what can be taught. We conclude by outlining our contribution to the literature on teaching EBMgt and by discussing limitations of our approach.

Behind the Scenes of an Ant Genome Project

Dramatic improvements in DNA sequencing technologies have led to amore than 1,000-fold reduction in sequencing costs over the past five years.Genome-wide research approaches can thus now be applied beyond medicallyrelevant questions to examine the molecular-genetic basis of behavior,development and unique life histories in almost any organism. A first step foran emerging model organism is usually establishing a reference genomesequence. I offer insight gained from the fire ant genome project. First, I detailhow the project came to be and how sequencing, assembly and annotationstrategies were chosen. Subsequently, I describe some of the issues linked toworking with data from recently sequenced genomes. Finally, I discuss anapproach undertaken in a follow-up project based on the fire ant genomesequence.

Evolution of decision-making and learning under fluctuating social environments

The capacity to learn to associate sensory perceptions with appropriate motor actions underlies the success of many animal species, from insects to humans. The evolutionary significance of learning has long been a subject of interest for evolutionary biologists who emphasize the bene¬fit yielded by learning under changing environmental conditions, where it is required to flexibly switch from one behavior to another. However, two unsolved questions are particularly impor¬tant for improving our knowledge of the evolutionary advantages provided by learning, and are addressed in the present work. First, because it is possible to learn the wrong behavior when a task is too complex, the learning rules and their underlying psychological characteristics that generate truly adaptive behavior must be identified with greater precision, and must be linked to the specific ecological problems faced by each species. A framework for predicting behavior from the definition of a learning rule is developed here. Learning rules capture cognitive features such as the tendency to explore, or the ability to infer rewards associated to unchosen actions. It is shown that these features interact in a non-intuitive way to generate adaptive behavior in social interactions where individuals affect each other's fitness. Such behavioral predictions are used in an evolutionary model to demonstrate that, surprisingly, simple trial-and-error learn¬ing is not always outcompeted by more computationally demanding inference-based learning, when population members interact in pairwise social interactions. A second question in the evolution of learning is its link with and relative advantage compared to other simpler forms of phenotypic plasticity. After providing a conceptual clarification on the distinction between genetically determined vs. learned responses to environmental stimuli, a new factor in the evo¬lution of learning is proposed: environmental complexity. A simple mathematical model shows that a measure of environmental complexity, the number of possible stimuli in one's environ¬ment, is critical for the evolution of learning. In conclusion, this work opens roads for modeling interactions between evolving species and their environment in order to predict how natural se¬lection shapes animals' cognitive abilities. - La capacité d'apprendre à associer des sensations perceptives à des actions motrices appropriées est sous-jacente au succès évolutif de nombreuses espèces, depuis les insectes jusqu'aux êtres hu¬mains. L'importance évolutive de l'apprentissage est depuis longtemps un sujet d'intérêt pour les biologistes de l'évolution, et ces derniers mettent l'accent sur le bénéfice de l'apprentissage lorsque les conditions environnementales sont changeantes, car dans ce cas il est nécessaire de passer de manière flexible d'un comportement à l'autre. Cependant, deux questions non résolues sont importantes afin d'améliorer notre savoir quant aux avantages évolutifs procurés par l'apprentissage. Premièrement, puisqu'il est possible d'apprendre un comportement incorrect quand une tâche est trop complexe, les règles d'apprentissage qui permettent d'atteindre un com¬portement réellement adaptatif doivent être identifiées avec une plus grande précision, et doivent être mises en relation avec les problèmes écologiques spécifiques rencontrés par chaque espèce. Un cadre théorique ayant pour but de prédire le comportement à partir de la définition d'une règle d'apprentissage est développé ici. Il est démontré que les caractéristiques cognitives, telles que la tendance à explorer ou la capacité d'inférer les récompenses liées à des actions non ex¬périmentées, interagissent de manière non-intuitive dans les interactions sociales pour produire des comportements adaptatifs. Ces prédictions comportementales sont utilisées dans un modèle évolutif afin de démontrer que, de manière surprenante, l'apprentissage simple par essai-et-erreur n'est pas toujours battu par l'apprentissage basé sur l'inférence qui est pourtant plus exigeant en puissance de calcul, lorsque les membres d'une population interagissent socialement par pair. Une deuxième question quant à l'évolution de l'apprentissage concerne son lien et son avantage relatif vis-à-vis d'autres formes plus simples de plasticité phénotypique. Après avoir clarifié la distinction entre réponses aux stimuli génétiquement déterminées ou apprises, un nouveau fac¬teur favorisant l'évolution de l'apprentissage est proposé : la complexité environnementale. Un modèle mathématique permet de montrer qu'une mesure de la complexité environnementale - le nombre de stimuli rencontrés dans l'environnement - a un rôle fondamental pour l'évolution de l'apprentissage. En conclusion, ce travail ouvre de nombreuses perspectives quant à la mo¬délisation des interactions entre les espèces en évolution et leur environnement, dans le but de comprendre comment la sélection naturelle façonne les capacités cognitives des animaux.

A new accelerometric method to assess the daily walking practice.

OBJECTIVE: To describe a method to obtain a profile of the duration and intensity (speed) of walking periods over 24 hours in women under free-living conditions. DESIGN: A new method based on accelerometry was designed for analyzing walking activity. In order to take into account inter-individual variability of acceleration, an individual calibration process was used. Different experiments were performed to highlight the variability of acceleration vs walking speed relationship, to analyze the speed prediction accuracy of the method, and to test the assessment of walking distance and duration over 24-h. SUBJECTS: Twenty-eight women were studied (mean+/-s.d.) age: 39.3+/-8.9 y; body mass: 79.7+/-11.1 kg; body height: 162.9+/-5.4 cm; and body mass index (BMI) 30.0+/-3.8 kg/m(2). RESULTS: Accelerometer output was significantly correlated with speed during treadmill walking (r=0.95, P<0.01), and short unconstrained walks (r=0.86, P<0.01), although with a large inter-individual variation of the regression parameters. By using individual calibration, it was possible to predict walking speed on a standard urban circuit (predicted vs measured r=0.93, P<0.01, s.e.e.=0.51 km/h). In the free-living experiment, women spent on average 79.9+/-36.0 (range: 31.7-168.2) min/day in displacement activities, from which discontinuous short walking activities represented about 2/3 and continuous ones 1/3. Total walking distance averaged 2.1+/-1.2 (range: 0.4-4.7) km/day. It was performed at an average speed of 5.0+/-0.5 (range: 4.1-6.0) km/h. CONCLUSION: An accelerometer measuring the anteroposterior acceleration of the body can estimate walking speed together with the pattern, intensity and duration of daily walking activity.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Medication use in pregnancy: a cross-sectional, multinational web-based study.

OBJECTIVES: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. DESIGN: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. SETTING: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. PARTICIPANTS: Pregnant women and new mothers with children less than 1 year of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. RESULTS: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. CONCLUSIONS: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.

Beyond the 'dyad': a qualitative re-evaluation of the changing clinical consultation.

OBJECTIVE: To identify characteristics of consultations that do not conform to the traditionally understood communication 'dyad', in order to highlight implications for medical education and develop a reflective 'toolkit' for use by medical practitioners and educators in the analysis of consultations. DESIGN: A series of interdisciplinary research workshops spanning 12 months explored the social impact of globalisation and computerisation on the clinical consultation, focusing specifically on contemporary challenges to the clinician-patient dyad. Researchers presented detailed case studies of consultations, taken from their recent research projects. Drawing on concepts from applied sociolinguistics, further analysis of selected case studies prompted the identification of key emergent themes. SETTING: University departments in the UK and Switzerland. PARTICIPANTS: Six researchers with backgrounds in medicine, applied linguistics, sociolinguistics and medical education. One workshop was also attended by PhD students conducting research on healthcare interactions. RESULTS: The contemporary consultation is characterised by a multiplicity of voices. Incorporation of additional voices in the consultation creates new forms of order (and disorder) in the interaction. The roles 'clinician' and 'patient' are blurred as they become increasingly distributed between different participants. These new consultation arrangements make new demands on clinicians, which lie beyond the scope of most educational programmes for clinical communication. CONCLUSIONS: The consultation is changing. Traditional consultation models that assume a 'dyadic' consultation do not adequately incorporate the realities of many contemporary consultations. A paradox emerges between the need to manage consultations in a 'super-diverse' multilingual society, while also attending to increasing requirements for standardised protocol-driven approaches to care prompted by computer use. The tension between standardisation and flexibility requires addressing in educational contexts. Drawing on concepts from applied sociolinguistics and the findings of these research observations, the authors offer a reflective 'toolkit' of questions to ask of the consultation in the context of enquiry-based learning.

The influence of the Internet on immunology education.

The potential of the Internet as a medium through which to teach basic and applied immunology lies in the ability to illustrate complex concepts in new ways for audiences that are diverse and often geographically dispersed. This article explores two collaborative Internet-based learning projects (also known as e-learning projects) that are under development: Immunology Online, which will present an Internet-based curriculum in basic and clinical immunology to Swiss undergraduate and graduate students across five campuses; and the OCTAVE project, which will offer online training to an international cadre of new investigators, the members of which are carrying out clinical trials of vaccines against HIV infection.

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The quality of environmental data analysis and propagation of errors are heavily affected by the representativity of the initial sampling design [CRE 93, DEU 97, KAN 04a, LEN 06, MUL07]. Geostatistical methods such as kriging are related to field samples, whose spatial distribution is crucial for the correct detection of the phenomena. Literature about the design of environmental monitoring networks (MN) is widespread and several interesting books have recently been published [GRU 06, LEN 06, MUL 07] in order to clarify the basic principles of spatial sampling design (monitoring networks optimization) based on Support Vector Machines was proposed. Nonetheless, modelers often receive real data coming from environmental monitoring networks that suffer from problems of non-homogenity (clustering). Clustering can be related to the preferential sampling or to the impossibility of reaching certain regions.