Structured benefit-risk assessment: a review of key publications and initiatives on frameworks and methodologies.

Introduction The conduct of structured benefit-risk assessment (BRA) of pharmaceutical products is a key area of interest for regulatory agencies and the pharmaceutical industry. However, the acceptance of a standardized approach and implementation are slow. Statisticians play major roles in these organizations, and have a great opportunity to be involved and drive the shaping of future BRA. Method We performed a literature search of recent reviews and initiatives assessing BRA methodologies, and grouped them to assist those new to BRA in learning, understanding, and choosing methodologies. We summarized the key points and discussed the impact of this emerging field on various stakeholders, particularly statisticians in the pharmaceutical industry. Results We provide introductory, essential, special interest, and further information and initiatives materials that direct readers to the most relevant materials, which were published between 2000 and 2013.  Based on recommendations in these materials we supply a toolkit of advocated BRA methodologies. Discussion Despite initiatives promoting these methodologies, there are still barriers, one of which being the lack of a consensus on the most appropriate methodologies among stakeholders. However, this opens up opportunities, for statisticians in the pharmaceutical industry especially, to champion appropriate BRA methodology use throughout the pharmaceutical product lifecycle. Conclusions This article may serve as a starting point for discussions and to reach a mutual consensus for methodology selection in a particular situation. Regulators and pharmaceutical industry should continue to collaborate to develop and take forward BRA methodologies, and by clear communication develop a mutual understanding of the key issues. Copyright © 2015 John Wiley & Sons, Ltd

Investigating the use of patient involvement and patient experience in quality improvement in Norway: rhetoric or reality?

Background Patient involvement in health care decision making is part of a wider trend towards a more bottom-up approach to service planning and provision, and patient experience is increasingly conceptualized as a core dimension of health care quality. The aim of this multi-level study is two-fold: 1) to describe and analyze how governmental organizations expect acute hospitals to incorporate patient involvement and patient experiences into their quality improvement (QI) efforts and 2) to analyze how patient involvement and patient experiences are used by hospitals to try to improve the quality of care they provide. Methods This multi-level case study combines analysis of national policy documents and regulations at the macro level with semi-structured interviews and non-participant observation of key meetings and shadowing of staff at the meso and micro levels in two purposively sampled Norwegian hospitals. Fieldwork at the meso and micro levels was undertaken over a 12-month period (2011–2012). Results Governmental documents and regulations at the macro level demonstrated wide-ranging expectations for the integration of patient involvement and patient experiences in QI work in hospitals. The expectations span from systematic collection of patients’ and family members’ experiences for the purpose of improving service quality through establishing patient-oriented arenas for ongoing collaboration with staff to the support of individual involvement in decision making. However, the extent of involvement of patients and application of patient experiences in QI work was limited at both hospitals. Even though patient involvement was gaining prominence at the meso level − and to a lesser extent at the micro level − relevant tools for measuring and using patient experiences in QI work were lacking, and available measures of patient experience were not being used meaningfully or systematically. Conclusions The relative lack of expertise in Norwegian hospitals of adapting and implementing tools and methods for improving patient involvement and patient experiences at the meso and micro levels mark a need for health care policymakers and hospital leaders to learn from experiences of other industries and countries that have successfully integrated user experiences into QI work. Hospital managers need to design and implement wider strategies to help their staff members recognize and value the contribution that patient involvement and patient experiences can make to the improvement of healthcare quality

Macrophage reprogramming for therapy.

Funder: MRC UK Dementia Research Institute ProfessorshipDysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage-targeted approaches in human disease

Unrelated Helpers in a Primitively Eusocial Wasp: Is Helping Tailored Towards Direct Fitness?

The paper wasp Polistes dominulus is unique among the social insects in that nearly one-third of co-foundresses are completely unrelated to the dominant individual whose offspring they help to rear and yet reproductive skew is high. These unrelated subordinates stand to gain direct fitness through nest inheritance, raising the question of whether their behaviour is adaptively tailored towards maximizing inheritance prospects. Unusually, in this species, a wealth of theory and empirical data allows us to predict how unrelated subordinates should behave. Based on these predictions, here we compare helping in subordinates that are unrelated or related to the dominant wasp across an extensive range of field-based behavioural contexts. We find no differences in foraging effort, defense behaviour, aggression or inheritance rank between unrelated helpers and their related counterparts. Our study provides no evidence, across a number of behavioural scenarios, that the behaviour of unrelated subordinates is adaptively modified to promote direct fitness interests

Beyond the Planar Limit in ABJM

In this article we consider gauge theories with a U(N)X U(N) gauge group. We provide, for the first time, a complete set of operators built from scalar fields that are in the bi fundamental of the two groups. Our operators diagonalize the two point function of the free field theory at all orders in 1/N. We then use this basis to investigate non-planar anomalous dimensions in the ABJM theory. We show that the dilatation operator reduces to a set of decoupled harmonic oscillators, signaling integrability in a nonplanar large N limit.Comment: v2: minor revisison

E-education in pathology including certification of e-institutions

E–education or electronically transferred continuous education in pathology is one major application of virtual microscopy. The basic conditions and properties of acoustic and visual information transfer, of teaching and learning processes, as well as of knowledge and competence, influence its implementation to a high degree. Educational programs and structures can be judged by access to the basic conditions, by description of the teaching resources, methods, and its program, as well as by identification of competences, and development of an appropriate evaluation system. Classic teaching and learning methods present a constant, usually non-reversible information flow. They are subject to personal circumstances of both teacher and student. The methods of information presentation need to be distinguished between static and dynamic, between acoustic and visual ones. Electronic tools in education include local manually assisted tools (language assistants, computer-assisted design, etc.), local passive tools (slides, movies, sounds, music), open access tools (internet), and specific tools such as Webinars. From the medical point of view information content can be divided into constant (gross and microscopic anatomy) and variable (disease related) items. Most open access available medical courses teach constant information such as anatomy or physiology. Mandatory teaching resources are image archives with user–controlled navigation and labelling, student–oriented user manuals, discussion forums, and expert consultation. A classic undergraduate electronic educational system is WebMic which presents with histology lectures. An example designed for postgraduate teaching is the digital lung pathology system. It includes a description of diagnostic and therapeutic features of 60 rare and common lung diseases, partly in multimedia presentation. Combining multimedia features with the organization structures of a virtual pathology institution will result in a virtual pathology education institution (VPEI), which can develop to a partly automated distant learning faculty in medicine

A double coset ansatz for integrability in AdS/CFT

We give a proof that the expected counting of strings attached to giant graviton branes in AdS_5 x S^5, as constrained by the Gauss Law, matches the dimension spanned by the expected dual operators in the gauge theory. The counting of string-brane configurations is formulated as a graph counting problem, which can be expressed as the number of points on a double coset involving permutation groups. Fourier transformation on the double coset suggests an ansatz for the diagonalization of the one-loop dilatation operator in this sector of strings attached to giant graviton branes. The ansatz agrees with and extends recent results which have found the dynamics of open string excitations of giants to be given by harmonic oscillators. We prove that it provides the conjectured diagonalization leading to harmonic oscillators.Comment: 33 pages, 3 figures; v2: references adde

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

BACKGROUND: Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS: Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n?=?863) at six, and 67% (n?=?810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS: SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions