Lessons learned in the development of process quality indicators for cancer care in Japan

In Japan, attention has increasingly focused on ensuring the quality of care, particularly in the area of cancer care. The 2006 Basic Cancer Control Act reinforced efforts to ensure the quality of cancer care in a number of sectors, including the role of government in ensuring quality. We initiated a government-funded research project to develop quality indicators to measure the quality of care for five major cancers (breast, lung, stomach, colorectal, and liver cancer) in Japan, and palliative care for cancers in general. While we successfully developed a total of 206 quality indicators, a number of issues have been raised regarding the concepts and methodologies used to measure quality. Examples include the choice between measuring the process of care versus the outcome of care; the degree to which the process-outcome link should be confirmed in real-world measurement; handling of exceptional cases; interpretation of measurement results between quality of care versus quality of documentation; creation of summary scores; and the optimal number of quality indicators for measurement considering the trade-off between the measurement validity versus resource limitations. These and other issues must be carefully considered when attempting to measure quality of care, and although many appear to have no correct answer, continuation of the project requires that a decision nevertheless be made. Future activities in this project, which is still ongoing, should focus on the further exploration of these problems.     

Development of an experiment-split method for benchmarking the generalization of a PTM site predictor: Lysine methylome as an example

Many computational classifiers have been developed to predict different types of post-translational modification sites. Their performances are measured using cross-validation or independent test, in which experimental data from different sources are mixed and randomly split into training and test sets. However, the self-reported performances of most classifiers based on this measure are generally higher than their performances in the application of new experimental data. It suggests that the cross-validation method overestimates the generalization ability of a classifier. Here, we proposed a generalization estimate method, dubbed experiment-split test, where the experimental sources for the training set are different from those for the test set that simulate the data derived from a new experiment. We took the prediction of lysine methylome (Kme) as an example and developed a deep learning-based Kme site predictor (called DeepKme) with outstanding performance. We assessed the experiment-split test by comparing it with the cross-validation method. We found that the performance measured using the experiment-split test is lower than that measured in terms of cross-validation. As the test data of the experiment-split method were derived from an independent experimental source, this method could reflect the generalization of the predictor. Therefore, we believe that the experiment-split method can be applied to benchmark the practical performance of a given PTM model. DeepKme is free accessible via https://github.com/guoyangzou/DeepKme.     

Use and influence of composite indicators for sustainable development at the EU-level

Considering the on-going strive towards new, alternative indicators to measure our societal development pathways, and the fact that policy indicators remain largely enigmatic with regard to their patterns of embeddedness in institutional decision-making processes, it appears necessary to work towards reducing our lack of understanding of their interactions with policy-making. In the present paper, we focus on exploring the significance of composite indicators for policy making in the particular policy environment of the EU-institutions. Our research is underpinned by the conviction that such indicators are not systematically used directly, but have an indirect influence on policy making that needs to be better understood. Our analytical framework – in order to analyse the ways in which composite indicators enter policy processes – is characterised by the distinction between the ‘use’ and the ‘influence’ of indicators on the one hand, and on the other hand between 3 types of factors: indicator factors, policy factors and user factors. Our empirical results show that while most of the academic attention and political debate around indicators has tended to focus on ‘indicator factors’, such quality attributes actually mattered relatively little in our setting as determinants of indicator influence. This rejects the idea that the robustness of evidence would lie exclusively in its technical quality and in the independence of its producer, and instead calls attention to the processes of evidence-construction. Simultaneously, ‘user factors’ (beliefs and representations of policy actors) and ‘policy factors’ (institutional context) were crucial as explanatory factors of the policy mechanics we identified.     

Management framework for sustainable development indicators in the State of Selangor, Malaysia

The perception that better information on environment and development is the determinant of effective rational decision- and policy-making processes provide the impetus for global interest in the use of sustainable development indicators (SDIs). Accordingly, proposals for SDIs are framed either on organisational goals or on disciplinary and multidisciplinary theories—aiming to reduce uncertainties in choosing the best alternative among a set of options concerning sustainability. Despite the fact that many SDI initiatives are explicitly aimed at improving policy-making, it is not apparent that political settings and organisational realities are taken into consideration in designing the framework for sustainability assessment. Ignoring the realities of policy-making dynamics can result in poor institutionalisation of the SDI development process, and therefore reduced impact of indicators. Linkage of SDIs to policy processes must also take into account the complex role of information in policy processes. The importance of societal values, cultural contexts and behaviour of bureaucracies must be understood and used to assist the assessment of progress towards sustainability using SDIs. Essentially, objective knowledge must be tampered with pragmatism in governance. This paper highlights the case of SDI development in the state of Selangor where the notion of instrumental rationality is balanced with the ‘incrementalism’ of the policy process that provided the foundation for institutionalising the reporting and use of SDIs. The ideals and paradoxes of participatory decision-making, the principles of the rational model and decision-making processes within a state government are critically examined.     

Investigating sex-biased migration during the Neolithic transition in Europe, using an explicit spatial simulation framework

Cultural practices can deeply influence genetic diversity patterns. The Neolithic transitions that took place at different times and locations around the world led to major cultural and demographic changes that influenced and therefore left their marks on human genetic diversity patterns. Several studies on the European Neolithic transition suggest that mitochondrial DNA (mtDNA) and Y-chromosome data can exhibit different patterns, which could be owing to different demographic histories for females and males. Archaeological and anthropological data suggest that the transition from hunter-gatherers (HGs) to farmers' societies is probably associated with changes in social organization, particularly in post-marital residence (PMR) rules (i.e. patrilocality, matrilocality or bilocality). The movements of humans and genes associated with these rules can be seen as sex-biased short-range migrations. We developed a new individual-based simulation approach to explore the genetic consequences of 45 different scenarios, where we varied the patterns of PMR and admixture between HGs and farmers. We recorded mtDNA and Y-chromosome data and analysed their diversity patterns within and between populations, through time and space. We also collected published mtDNA and Y-chromosome data from European and Near-Eastern populations in order to identify the scenarios that would best explain them. We show that: (i) different PMR systems can lead to different patterns of genetic diversity and differentiation, (ii) asymmetries between mtDNA and Y-chromosome can be owing to different behaviours between males and females, but also to different mutations rates, and (iii) patrilocality in farmers explains the present patterns of genetic diversity better than matrilocality or bilocality. Moreover, we found that (iv) the genetic diversity of farmers change depending on the HGs PMR rules even though they are assumed to disappear more than 5000 years ago in our simulations.     

Improving the quality of care for infants: a cluster randomized controlled trial

Background

We developed and tested a new method, called the Evidence-based Practice for Improving Quality method, for continuous quality improvement.

Methods

We used cluster randomization to assign 6 neonatal intensive care units (ICUs) to reduce nosocomial infection (infection group) and 6 ICUs to reduce bronchopulmonary dysplasia (pulmonary group). We included all infants born at 32 or fewer weeks gestation. We collected baseline data for 1 year. Practice change interventions were implemented using rapid-change cycles for 2 years.

Results

The difference in incidence trends (slopes of trend lines) between the ICUs in the infection and pulmonary groups was − 0.0020 (95% confidence interval [CI] − 0.0007 to 0.0004) for nosocomial infection and − 0.0006 (95% CI − 0.0011 to − 0.0001) for bronchopulmonary dysplasia.

Interpretation

The results suggest that the Evidence-based Practice for Improving Quality method reduced bronchopulmonary dysplasia in the neonatal ICU and that it may reduce nosocomial infection.Although methods for continuous quality improvement have been used to improve outcomes,^1–3 some, such as the National Institutes of Child Health and Human Development Quality Collaborative,⁴ have reported little or no effect in neonatal intensive care units (ICUs). These methods have been criticized for being based on intuition and anecdotes rather than on evidence.⁵ To address these concerns, researchers have developed methods aimed at improving the use of evidence in quality improvement. Tarnow-Mordi and colleagues,⁶ Sankaran and colleagues⁷ and others^8–10 have used benchmarking instruments^6,8,11 to show risk-adjusted variations in outcomes in neonatal ICUs. Synnes and colleagues¹² reported that variations in the rates of intraventricular hemorrhage could be attributed to practice differences. MacNab and colleagues¹³ showed how multilevel modelling methods can be used to identify practice differences associated with variations in outcomes for targeted interventions and to quantify their attributable risks.Building on these results, we developed the Evidence-based Practice for Improving Quality method for continuous quality improvement. This method is based on 3 pillars: the use of evidence from published literature; the use of data from participating hospitals to identify hospital-specific practices for targeted intervention; and the use of a national network to share expertise. By selectively targeting hospital-specific practices for intervention, this method reduces the reliance on intuition and anecdotes that are associated with existing quality-improvement methods.Our objective was to evaluate the efficacy of the Evidence-based Practice for Improving Quality method by conducting a prospective cluster randomized controlled trial to reduce nosocomial infection and bronchopulmonary dysplasia among infants born at 32 or fewer weeks’ gestation and admitted to 12 Canadian Neonatal Network hospitals¹⁴ over a 36-month period. We hypothesized that the incidence of nosocomial infection would be reduced among infants in ICUs randomized to reduce infection but not among those in ICUs randomized to reduce bronchopulmonary dysplasia. We also hypothesized that the incidence of bronchopulmonary dysplasia would be reduced among infants in the ICUs randomized to reduce this outcome but not among those in ICUs randomized to reduce infections.     

Optimal foraging behavior with an explicit consideration of within-individual behavioral variation: an example of predation

Animal behavior is flexible, and the same individual can exhibit variable expressions under the equivalent ecological situations (i.e., within-individual behavioral variation). This study examines the evolution of within-individual behavioral variation using an individual-based model. A common predation scenario is considered where a predator spends a period h to handle and consume a captured prey. The model assumes the handling time of the predator to be a random variable. The average and within-individual variance of handling time are described by \(\mu _h\) and \(\sigma _h^2\), respectively, where each individual has its own unique \(\mu _h\) and \(\sigma _h^2\). Using a genetic algorithm, the evolution of \(\sigma _h^2\) is traced. The results show that natural selection acts on both \(\mu _h\) and \(\sigma _h^2\), and the optimal behavioral variation depends on the density of prey. In particular, individuals with high behavioral variance \(\sigma _h^2\) are more likely selected when prey density is low. Individual based modeling can be a useful tool for studying the ultimate significance of within-individual behavioral variation and generating empirically testable predictions. The mechanisms of the evolution of within-individual behavioral variation and their ecological implications are discussed.     

Improving the quality of care via maintenance of certification and the Web: an early status report

Few question the need for continuous professional development throughout a physician's career, but rapid changes in health care are creating demand for physicians to acquire new knowledge, skills, and attitudes to implement quality improvement in clinical practice. The Internet and World Wide Web are technologies that have the potential to facilitate deep change in physician practice and lifelong learning. This paper describes how the American Board of Internal Medicine (ABIM) has utilized the Web and the Internet to engage physicians in the competencies of practice-based learning and improvement and systems-based practice. Specifically, we describe how the ABIM developed and implemented Web-based practice improvement modules (PIMs) to help physicians measure and improve their clinical practice.     

Phylloclade development in the Asparagaceae: an example of homoeosis

Phylloclades are traditionally defined as flattened, determinate, leaf-like stems primarily on the basis of their axillary position. However, because the literature is replete with controversy over the morphological interpretation of these organs, a study of phylloclade development in comparison with leaf and stem development was undertaken in four closely related species of the Asparagaceae: Ruscus aculeatus, Danae racemosa, Semele androgyna and Asparagus densiflorus. Results reveal a continuum in phylloclade development from very leaf-like forms, such as those of Danae, via the more intermediate types of Ruscus, to the gradually more shootlike forms of Semele and Asparagus. This continuum results from a differential expression of stem (or shoot) and leaf characteristics in an axillary position. When stem (or shoot) and leaf features are combined, as in the fertile phylloclade of Ruscus, an intermediate organ is formed. Phylloclades are a form of evolutionary novelty that exemplifies the phenomenon of homoeosis, which is the transference of features from one organ to another. Developmentally, this means that leaf features are expressed by the axillary meristem.     

Phylloclade development in the Asparagaceae: an example of homoeosis

Phylloclades are traditionally defined as flattened, determinate, leaf-like stems primarily on the basis of their axillary position. However, because the literature is replete with controversy over the morphological interpretation of these organs, a study of phylloclade development in comparison with leaf and stem development was undertaken in four closely related species of the Asparagaceae: Ruscus aculeatus, Danae racemosa, Semele androgyna and Asparagus densiflorus. Results reveal a continuum in phylloclade development from very leaf-like forms, such as those of Danae , via the more intermediate types of Ruscus , to the gradually more shootlike forms of Semele and Asparagus. This continuum results from a differential expression of stem (or shoot) and leaf characteristics in an axillary position. When stem (or shoot) and leaf features are combined, as in the fertile phylloclade of Ruscus , an intermediate organ is formed. Phylloclades are a form of evolutionary novelty that exemplifies the phenomenon of homoeosis, which is the transference of features from one organ to another. Developmentally, this means that leaf features are expressed by the axillary meristem.     

Rapid development of multiple nuclear loci for phylogenetic analysis using genomic resources: an example from squamate reptiles

Recently, as genome-scale data have become available for more organisms, the development of phylogenetic markers from nuclear protein-coding loci (NPCL) has become more tractable. However, new methods are needed to efficiently sort the large number of genes from genomic databases into more limited sets appropriate for particular phylogenetic questions, while avoiding introns and paralogs. Here we describe a general methodology for identifying candidate single-copy NPCL from genomic databases. Our method uses information from reference genomes to identify genes with relatively large continuous protein-coding regions (i.e., 700bp). BLAST comparisons are used to help avoid genes with paralogous copies or close relatives (i.e., gene families) that might confound phylogenetic analyses. Exon boundary information is used to identify appropriately spaced potential priming sites. Using this method, we have developed over 25 novel NPCL, which span a variety of desirable evolutionary rates for phylogenetic analyses. Although targeted for higher-level phylogenetics of squamate reptiles, many of these loci appear to be useful across and within other vertebrate clades (e.g., amphibians), and some are relatively rapidly evolving and may be useful for closely-related species (e.g., within genera). This general method can be used whenever large-scale genomic data are available for an appropriate reference species (not necessarily within the focal clade). The method is also well suited for the development of intron regions for lower-level phylogenetic and phylogeographic studies. We provide an online database of alignments and suggested primers for approximately 85 NPCL that should be useful across vertebrates.     

Towards an automated system for the identification of notifiable pathogens: using as an example.

Simple and rapid identification of pathogen species is crucial to the control of many diseases. Here, James Kay, Andrew Shinn and Christina Sommerville demonstrate that statistical classifiers discriminate a notifiable pathogen Gyrodactylus salaris Malmberg, 1957, a lethal ectoparasite of Atlantic salmon, Salmo salar L., from its benign close relatives.     

Improving quality of care: focus on liaison old age psychiatry

Introduction Elderly patients occupy up to 65% of acute hospital beds and a significant proportion of them present with a comorbid psychiatric condition such as depression, delirium or dementia. Liaison old age psychiatry (LOAP) services have been developed to provide psychiatric consultation in medical and surgical settings, improving at the same time the knowledge and expertise of general ward staff.Objective The aim of this study is to evaluate clinical characteristics across different psychiatric disorders among elderly patients in medical wards.Method A prospective observational study was developed between October 2011 and January 2013, which involved 107 subjects aged 65 years or older that were hospitalised in the Department of Internal Medicine and referred to the LOAP service. Psychiatric diagnostic was assessed using the Confusion Assessment Method, the Geriatric Depression Scale, the Mini-Mental State Examination and the Clinical Global Impression Scale.Results Delirium (40.6%), depression (22.4%) and dementia (20.4%) were the most common psychiatric diagnoses. Patients with delirium were significantly older, had more severe psychiatric symptomatology (mean CGI = 5.35) and presented infectious processes as acute medical conditions more frequently than the other patients.Conclusion Psychiatric disturbances occurring in elderly inpatients in medical wards are highly prevalent and complex. A LOAP service may play an important role in effectively reducing the overutilisation and consumption of health resources through early recognition of these conditions, effective management and prevention of adverse outcomes, and effective communication with out-patient clinics, community mental health teams and day-care centres.     

Biodiversity indicators for sustainability monitoring at municipality level: An example of implementation in an alpine region

As is laid down in the convention on biodiversity, it is essential to install a sustainability monitoring system with integrated biodiversity indicators on both the regional and local levels. The resulting data derived from such a system would be instrumental in supporting the work of policy- and decision-makers as well as stakeholders. However, the integration of biodiversity indicators on the local level is still uncommon. Our aim was therefore to produce a set of biodiversity indicators that: (1) reflects all requirements for regional sustainability monitoring on the municipality level and (2) enables the derived multifaceted information to be simplified and used to improve the applicability and implementation of the system. To this end, we also aimed to assess the validity of the selected indicators in a case study area. Together with a team of 20 local experts composed of officials, stakeholders and scientists, we selected five common biodiversity indicators: landscape diversity, undissected landscape, hemeroby, naturalness of the riparian area and agricultural intensity. In addition, to describe the quality of an area in terms of the richness of species living in it, we developed two further indicators ‘area weighted mean species richness of vascular plants’ and ‘frequency weighted absolute species richness of vascular plants’. In terms of practical and political implementation, we also defined theory-based desired levels, from which we derived performance rates.The study was carried out in 2004 for each of the 116 municipalities of South Tyrol, an alpine region in northern Italy and data were analysed using a maximum likelihood estimation (spatial lag model). The results clearly showed that the large variance of indicator values mainly arises from anthropogenic activities, and that all indicators are robust to spatial extent, and thus appropriate for multiscale assessment. Further, applying a factor analysis allowed three dimensions to be identified that account for more than 76% of the total variance: (1) naturalness, (2) landscape structure and (3) species diversity. Hence, factor analysis is an objective approach to reduce the number of indicators without loosing too much information. However, it should be borne in mind that for specific ecological questions, the use of single indicators is still inevitable.     

Selecting biological indicators for monitoring soils: A framework for balancing scientific and technical opinion to assist policy development

Soils are one of the most important features of the natural capital of terrestrial ecosystems. There is a strong and increasing policy requirement for effective monitoring of soils at local, regional and national-scales. However, it remains unclear which properties of soils are most appropriately monitored. This is partly due to the wide range of goods and services that soils provide, but also their inherent chemical, physical and biological complexity. Given that the biota plays such fundamental roles in the majority of ecosystem services provided by soils, biological properties are logical candidates as effective indicators, to complement soil physico-chemical properties. A plethora of biological methods have been suggested as indicators for monitoring soils but few are used in national-scale monitoring or are published as international standards. A framework for selecting ecologically relevant biological indicators of soil quality, for national-scale soil monitoring, that cover the range of functions and services of soil was devised. The literature was surveyed to identify 183 candidate biological indicators which were then scored by experts and stakeholders against a wide range of scientific and technical criteria. The framework used the scores and weightings to then rank, prioritise and select the indicators. This semi-objective approach using a “logical sieve” allowed repeated iterations to take account of end-user requirements and expert opinion. A ranked list of 21 indicators was produced that covered a range of genotypic-, phenotypic- and functional-based indicators for different trophic groups. Four of these were not deemed sufficiently robust for ready deployment in a national-scale monitoring scheme without further methodological development. The suite of indicators identified offers the strongest potential candidates for deployment in national-scale soil monitoring schemes. However, standard operating procedures, their inherent sensitivity, ability to discriminate between soil:land use combinations, ecological interpretation all need to be confirmed. The power of the approach adopted here is that it provides a clear record and audit trail on the decision-making process, enables different priorities to be set contingent on the nature of the desired monitoring, and can direct and allow the inclusion of further methods or indicators into the framework.     

Towards a common framework for defining ancillary material quality across the development spectrum

Ancillary materials (AMs) play a critical role in the manufacture of cell and gene therapies, and best practices for their quality management are the subject of ongoing discussion. Given that the final product cannot be sterilized, AM quality becomes increasingly critical to the clinical advancement of cell and gene therapies. Despite a lack of direct legislative direction regarding AM quality, internationally harmonized guidance is available from several industry-standard bodies that describe the principles and application of a risk-based approach to AM qualification and related supply-chain risk management. According to a best-practice risk-based approach, AMs must be adequately qualified to a degree that reflects the level of risk the material presents to patient safety and the drug product's specification. This general approach can be implemented in different ways, and balancing quality with cost of goods is critical to the cost-effective manufacture of advanced therapy medicinal products. In some cases, it may be preferable or necessary to use AMs that are produced in compliance with current Good Manufacturing Practice. However, developers may be able to suppress manufacturing costs without undermining safety or regulatory compliance in the case that a material presents a lower risk profile. Despite a great deal of attention and interest in the quality of AMs in the cell and gene therapy space, there is still a need for greater harmonization to create a shared understanding of what constitutes a risk-based approach to AM production and sourcing. In this article, we propose a staged approach to AM quality that achieves a balance between the competing demands of risk mitigation and cost of goods containment at the various stages of AM quality development. Our novel, heuristic framework for communication among AM suppliers, users and regulators aims to bring down development and manufacturing costs and lessen the workload around regulatory compliance.