Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review

BACKGROUND: Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials. OBJECTIVES: In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported. METHODS: We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen. RESULTS: We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good. CONCLUSIONS: Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.

Treatment issues in spontaneous cervicocephalic artery dissections

The management of cervicocephalic arterial dissections raises many unsolved issues such as: how to best acutely treat patients who present with ischemic stroke or occasionally with sub-arachnoid hemorrhage? How to best prevent ischemic stroke in patients who present with purely local signs such as headache, painful Horner Syndrome or neck pain? How long and how should patients be treated after cervicocephalic arterial dissections? Can patients resume their sports activities and when? The consensus is that, given the well-established initial thromboembolic risk, an urgent antithrombotic treatment is required in patients with a recent nonhemorrhagic cervicocephalic arterial dissection, but the type of antithrombotic treatment - anticoagulants or aspirin - as well as the indication for a local arterial treatment such as angioplasty/stenting remain debated. Evidence from a randomized clinical trial would be welcome but such a trial raises major issues of methodology, feasibility and funding. Meanwhile, cervicocephalic arterial dissection remains a situation when a bedside clinician should use, on a case-by-case basis, best clinical judgment and adopt a stepped care approach in the minority of patients who deteriorate despite initial treatment.

Tooth wear and erosion: methodological issues in epidemiological and public health research and the future research agenda

This paper addresses methodological issues in the field of tooth wear and erosion research including the epidemiological indices, and identifies future work that is needed to improve knowledge about tooth wear and erosion.

'New perspectives on well-known issues': patients' experiences and perceptions of safety in Swiss hospitals

Patients' reports of safety-related events and perceptions of safety can be a valuable source for hospitals. Patients of eight acute care hospitals in Switzerland were surveyed for safety-related events and concerns for safety. In workshops with hospitals areas for improvement were analyzed and priorities for change identified. To evaluate the benefit of the approach, semi-structured interviews were conducted with hospital risk managers. 3,983 patients returned the survey (55% response rate). 21.4% reported at least one definite safety event, and the mean number of 'definite' incidents per patient was 0.31 (95% CI=0.29 to 0.34). 3.2% were very concerned and 14.7% were somewhat concerned about medical errors and safety. Having experienced a safety-related event, younger age, length of stay, poor health and a poor education increased the probability of reporting concerns. With some exceptions, results confirmed the hospitals' a priori expectations regarding the strengths and weaknesses of their institutions. Risk managers emphasized the usability of results for their work and the special value of referring to the patient's perspective at their home institutions. A considerable fraction of patients subjectively experiences safety-related events and is concerned about safety. Patient-generated data introduced a new quality into the discussion of safety issues within hospitals, and some expected that patients' experiences and concerns could affect patient volumes. Though the study is limited by the short time horizon and the lack of follow-up, the results suggest that the described approach is feasible and can serve as a supplemental tool for risk identification and management.

Methodological issues in quantifying the magnitude of the tuberculosis problem in a prison population

SETTING: Correctional settings and remand prisons. OBJECTIVE: To critically discuss calculations for epidemiological indicators of the tuberculosis (TB) burden in prisons and to provide recommendations to improve study comparability. METHODS: A hypothetical data set illustrates issues in determining incidence and prevalence. The appropriate calculation of the incidence rate is presented and problems arising from cross-sectional surveys are clarifi ed. RESULTS: Cases recognized during the fi rst 3 months should be classifi ed as prevalent at entry and excluded from any incidence rate calculation. The numerator for the incidence rate includes persons detected as having developed TB during a specifi ed period of time subsequent to the initial 3 months. The denominator is persontime at risk from 3 months onward to the end point (TB or end of the observation period). Preferably, entry time, exit time and event time are known for each inmate to determine person-time at risk. Failing that, an approximation consists of the sum of monthly head counts, excluding prevalent cases and those persons no longer at risk from both the numerator and the denominator. CONCLUSIONS: The varying durations of inmate incarceration in prisons pose challenges for quantifying the magnitude of the TB problem in the inmate population. Recommendations are made to measure incidence and prevalence.

The Mediterranean climate: An overview of the main characteristics and issues

The Mediterranean Region has many morphologic, geographical, historical, and societal characteristics, which make its climate scientifically interesting. The concept of Mediterranean climate is characterized by mild wet winters and warm to hot, dry summers and occur on the west side of continents between about 30° and 40° latitude. However, the presence of a relatively large mass of water is unique to the actual Mediterranean region. The Mediterranean Sea is a marginal and semi-enclosed sea; it is located on the western side of a large continental area and is surrounded by Europe to the North, Africa to the South, and Asia to the East. The chapter discusses that the climate of the Mediterranean region is to a large extent forced by planetary scale patterns. The time and space behavior of the regional features associated with such large-scale forcing is complex. Orography and land–sea distribution play an important role establishing the climate at basin scale and its teleconnections with global patterns. Different levels of services of readiness to emergencies, technological, and economic resources are likely to result in very different adaptation capabilities to environmental changes and new problems. The different economic situations and demographic trends are likely to produce contrasts and conflicts in a condition of limited available resources and environmental stress.

Imaging emotional brain functions: conceptual and methodological issues

This article reviews the psychophysiological and brain imaging literature on emotional brain function from a methodological point of view. The difficulties in defining, operationalising and measuring emotional activation and, in particular, aversive learning will be considered. Emotion is a response of the organism during an episode of major significance and involves physiological activation, motivational, perceptual, evaluative and learning processes, motor expression, action tendencies and monitoring/subjective feelings. Despite the advances in assessing the physiological correlates of emotional perception and learning processes, a critical appraisal shows that functional neuroimaging approaches encounter methodological difficulties regarding measurement precision (e.g., response scaling and reproducibility) and validity (e.g., response specificity, generalisation to other paradigms, subjects or settings). Since emotional processes are not only the result of localised but also of widely distributed activation, a more representative model of assessment is needed that systematically relates the hierarchy of high- and low-level emotion constructs with the corresponding patterns of activity and functional connectivity of the brain.

[Effects of tobacco use on systemic health: relevant information for dentistry (II)--part 2: cardiovascular diseases and public health issues]

This is the sixth and concluding part of a series of publications from the Swiss task force named "Smoking - Intervention in the private dental office" on the topic "tobacco use and dental medicine". The focus of this review is the effects of smoking for the development of atherosclerosis as pathohistological correlate for acute coronary syndrome (ACS), arterial occlusive disease, and cerebrovascular diseases (stroke). Additionally, a causal relationship between tobacco use and an increased rate for complications during pregnancy and child birth will be discussed. Next to causal therapy of local and systemic diseases in general, an emphasis must be given to tobacco use prevention and cessation. Finally, important public health issues concerning smoking and tobacco use will be demonstrated, and options to improve the current situation will be presented.

Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts

In spite of the facts that magnetic resonance spectroscopy (MRS) is applied as clinical tool in non-specialized institutions and that semi-automatic acquisition and processing tools can be used to produce quantitative information from MRS exams without expert information, issues of spectral quality and quality assessment are neglected in the literature of MR spectroscopy. Even worse, there is no consensus among experts on concepts or detailed criteria of quality assessment for MR spectra. Furthermore, artifacts are not at all conspicuous in MRS and can easily be taken for true, interpretable features. This article aims to increase interest in issues of spectral quality and quality assessment, to start a larger debate on generally accepted criteria that spectra must fulfil to be clinically and scientifically acceptable, and to provide a sample gallery of artifacts, which can be used to raise awareness for potential pitfalls in MRS.

Critical issues in managing protected areas by multi-stakeholder participation - analysis of a process in the Swiss Alps

Balancing the frequently conflicting priorities of conservation and economic development poses a challenge to management of the Swiss Alps Jungfrau-Aletsch World Heritage Site (WHS). This is a complex societal problem that calls for a knowledge-based solution. This in turn requires a transdisciplinary research framework in which problems are defined and solved cooperatively by actors from the scientific community and the life-world. In this article we re-examine studies carried out in the region of the Swiss Alps Jungfrau-Aletsch WHS, covering three key issues prevalent in transdisciplinary settings: integration of stakeholders into participatory processes; perceptions and positions; and negotiability and implementation. In the case of the Swiss Alps Jungfrau-Aletsch WHS the transdisciplinary setting created a situation of mutual learning among stakeholders from different levels and backgrounds. However, the studies showed that the benefits of such processes of mutual learning are continuously at risk of being diminished by the power play inherent in participatory approaches.

Tackling Software Navigation Issues of the Smalltalk IDE

The IDE used in most Smalltalk dialects such as Pharo, Squeak or Cincom Smalltalk did not evolve significantly over the last years, if not to say decades. For other languages, for instance Java, the available IDEs made tremendous progress as Eclipse or NetBeans illustrate. While the Smalltalk IDE served as an exemplar for many years, other IDEs caught up or even overtook the erstwhile leader in terms of feature-richness, usability, or code navigation facilities. In this paper we first analyze the difficulty of software navigation in the Smalltalk IDE and second illustrate with concrete examples the features we added to the Smalltalk IDE to fill the gap to modern IDEs and to provide novel, improved means to navigate source space. We show that thanks to the agility and dynamics of Smalltalk, we are able to extend and enhance with reasonable effort the Smalltalk IDE to better support software navigation, program comprehension, and software maintenance in general. One such support is the integration of dynamic information into the static source views we are familiar with. Other means include easing the access to static information (for instance by better arranging important packages) or helping developers re-locating artifacts of interest (for example with a categorization system such as smart groups).

[Mass culling in the context of animal disease outbreaks--veterinarians caught between ethical issues and control policies]

In recent years controversial discussions arose during major animal disease outbreaks in the EU about the ethical soundness of mass culling. In contrast to numerous publications about ethical issues and laboratory animals/animal experiments, literature concerning ethical deliberations in the case of mass culling as a means of outbreak control remain scarce. Veterinarians in charge of decision about and implementation of mass culling actions find themselves in an area of conflict in between the officially required animal disease control policy and a public that is increasingly critical. Those veterinarians are faced with the challenge to defend the relevant decisions against all stakeholders and also themselves. In this context an interdisciplinary workshop was initiated in Switzerland in October 2007 with ethicians and (official) veterinarians from Germany, Switzerland and Austria. With the aim to identify ethical components of animal disease control for official veterinarians, talks and moderated group discussions took place. This article summarizes selected discussion points and conclusions.

Corporate dividencs and seasoned equity issues: an empirical investigation

This paper investigates whether managers rely on dividends to obtain a higher price in a stock offering and whether the stock price reaction to dividend and offering announcements justifies such a coordination. The evidence does not support either conjecture. Issuing firms are not more likely to pay or increase dividends than nonissuing forms. Moreover, there is little evidence that firms time stock offering announcements right after dividend declarations to befefit from the attendant information disclosure. The analysis of dividend and stock offering announcement effects suggests few if any benefits from linking divbidend and stock offering announcements.

Cluster randomized clinical trials in orthodontics: design, analysis and reporting issues

Cluster randomized trials (CRTs) use as the unit of randomization clusters, which are usually defined as a collection of individuals sharing some common characteristics. Common examples of clusters include entire dental practices, hospitals, schools, school classes, villages, and towns. Additionally, several measurements (repeated measurements) taken on the same individual at different time points are also considered to be clusters. In dentistry, CRTs are applicable as patients may be treated as clusters containing several individual teeth. CRTs require certain methodological procedures during sample calculation, randomization, data analysis, and reporting, which are often ignored in dental research publications. In general, due to similarity of the observations within clusters, each individual within a cluster provides less information compared with an individual in a non-clustered trial. Therefore, clustered designs require larger sample sizes compared with non-clustered randomized designs, and special statistical analyses that account for the fact that observations within clusters are correlated. It is the purpose of this article to highlight with relevant examples the important methodological characteristics of cluster randomized designs as they may be applied in orthodontics and to explain the problems that may arise if clustered observations are erroneously treated and analysed as independent (non-clustered).

Is there good simulation basic training for end-to-side vascular microanastomoses?

BACKGROUND Microvascular anastomosis is the cornerstone of free tissue transfers. Irrespective of the microsurgical technique that one seeks to integrate or improve, the time commitment in the laboratory is significant. After extensive previous training on several animal models, we sought to identify an animal model that circumvents the following issues: ethical rules, cost, time-consuming and expensive anesthesia, and surgical preparation of tissues required to access vessels before performing the microsurgical training, not to mention that laboratories are closed on weekends. METHODS Between January 2012 and April 2012, a total of 91 earthworms were used for 150 microsurgical training exercises to simulate vascular end-to-side microanastomosis. The training sessions were divided into ten periods of 7 days. Each training session included 15 simulations of end-to-side vascular microanastomoses: larger than 1.5 mm (n=5), between 1.0 and 1.5 mm (n=5), and smaller than 1.0 mm (n=5). A linear model with the main variables being the number of weeks (as a numerical covariate) and the size of the animal (as a factor) was used to determine the trend in time of anastomosis over subsequent weeks as well as the differences between the different size groups. RESULTS The linear model shows a significant trend (p<0.001) in time of anastomosis in the course of the training, as well as significant differences (p<0.001) between the groups of animals of different sizes. For microanastomoses larger than 1.5 mm, the mean anastomosis time decreased from 19.3±1.0 to 11.1±0.4 min between the first and last week of training (decrease of 42.5%). For training with smaller diameters, the results showed a decrease in execution time of 43.2% (diameter between 1.0 and 1.5 mm) and 40.9% (diameter<1.0 mm) between the first and last periods. The study demonstrates an improvement in the dexterity and speed of nodes execution. CONCLUSION The earthworm appears to be a reliable experimental model for microsurgical training of end-to-side microanastomoses. Its numerous advantages are discussed here and we predict training on earthworms will significantly grow and develop in the near future. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .