Letter to the Editor re "Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion"

High-quality patient care can be defined as an approach that minimizes harm whilst aligning with people's expectations. Dying people and their relatives have articulated that they expect health care providers to manage physical and psychological symptoms well, with expectations even higher when such care is delivered by specialist services. Despite excellent intentions, palliative care clinicians and researchers have done little to improve systematically the evidence base for prescribing when people are actually dying. Few data exist to inform clinicians' understanding of how people's actual experiences align with their articulated wishes. Symptoms are managed based on relatives' and staff's assumptions of the experience of the dying person, with a “good death” often being seen as quiet and calm. Achieving this often requires sedation, for which the dying person will very rarely have given consent. This requires consideration, especially when evidence suggests people facing death will forgo symptom control to remain as alert and interactive for as long as possible. We ignore patients' wishes at our peril if we are to be truly patient centered

End-of-life research: do we need to build proxy consent into all clinical trial protocols studying the terminal phase?

Research into symptoms that occur at the end of life is paramount for ensuring we provide the best possible care for patients in the terminal phase, yet obtaining informed consent from the study participant is not possible at the time these symptoms occur. Importantly, these questions cannot be answered in any clinical population and defining the net clinical effect of medications used, for example, for noisy respiratory secretions is crucial if the quality of care is to be further improved

Acceptance In Stuttering Therapy: A Clinician Perspective

The present study explores the concept of stuttering acceptance by examining the point of view of speech-language pathologists who treat people who stutter. Three main questions were posed: 1) How do speech-language pathologists define acceptance in regards to stuttering? 2) Is acceptance of stuttering important in therapy, and why is it important? 3) How is acceptance of stuttering addressed in therapy? In interviewing six therapists that work specifically with clients who stutter, stuttering acceptance was identified as being multifaceted and vital to the ultimate success of therapy for those who stutter. Each participant shared how they address acceptance of stuttering in therapy. The results of this study clarified the concept of acceptance in stuttering therapy from the clinician perspective in addition to providing a basic, positive therapeutic framework for clients who stutter across the lifespan. Findings indicate that acceptance of stuttering involves clients’ (1) understanding that stuttering and its management is variable, (2) being able to tolerate moments of stuttering, and (3) having a positive self-perception

Informed consent in palliative care clinical trials: challenging but possible

Obtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability

Clinically significant depressive symptoms are prevalent in people with extremely short prognoses - A systematic review

Context: Currently, systematic evidence of prevalence of clinically significant depressive symptoms in people with extremely short prognoses is not available to inform its global burden, assessment, and management. Objectives: To determine the prevalence of clinically significant depressive symptoms in people with advanced life-limiting illnesses and extremely short prognoses (range of days to weeks). Methods: A systematic review and meta-analysis (random effects model) were performed (PROSPERO: CRD42019125119). MEDLINE, Embase, PsycINFO, CINAHL, and CareSearch were searched for studies (1994-2019). Data were screened for prevalence of clinically significant depressive symptoms (assessed using validated depression-specific screening tools or diagnostic criteria) of adults with advanced life-limiting illnesses and extremely short prognoses (defined by survival or functional status). Quality assessment was performed using the Joanna Briggs Institute Systematic Reviews Checklist for Prevalence Studies for individual studies, and Grading of Recommendations Assessment, Development and Evaluation (GRADE) across studies. Results: Thirteen studies were included. The overall pooled prevalence of clinically significant depressive symptoms in adults with extremely short prognoses (n = 10 studies; extremely short prognoses: N = 905) using depression-specific screening tools was 50% (95%CI: 29%-70%; I2 = 97.6%). Prevalence of major and minor depression were 10% (95%CI: 4%-16%) and 5% (95%CI: 2%-8%), respectively. Major limitations included high heterogeneity, selection bias and small sample sizes in individual studies. Conclusions: Clinically significant depressive symptoms were prevalent in people with advanced life-limiting illnesses and extremely short prognoses. Clinicians need to be proactive in the recognition and assessment of these symptoms to allow for timely intervention

Older persons’ and their caregivers’ perspectives and experiences of research participation with impaired decision-making capacity: A scoping review

Background and Objectives: Human research ethics statements support equitable inclusion of diverse groups. Yet older people are under-represented in clinical research, especially those with impaired decision-making capacity. The aim of this study was to identify perspectives and experiences of older persons and their caregivers of research participation with impaired decision-making capacity. Research Design and Methods: Scoping review of literature and online sources in January-February 2019 (updated June 2020) according to Joanna Briggs Institute methodology and PRISMA Extension for Scoping Reviews. English-language peer-reviewed research articles and Australian online narratives were included. Data were tabulated and narratively synthesized. Results: From 4171 database records and 93 online resources, 22 articles (2000-2019, 82% United States, 16 first authors) and one YouTube webinar (2018) were initially included; updated searches yielded an additional article (2020) and YouTube webinar (2020). Studies were heterogeneous in terminology, methods and foci, with hypothetical scenarios, quantitative analyses and examination of proxy consent predominating. Participants (n=7331) were older persons (71%), caregivers of older persons with dementia/cognitive impairment (23%) and older persons with dementia/cognitive impairment (6%). Synthesis identified two themes: willingness to participate and decision-making approaches. Discussion and Implications: Research participation by older persons with dementia may be optimized through reducing risks and burdens and increasing benefits for participants, greater consumer input into study development, and shared and supported decision-making. Older persons’ and caregivers’ perspectives and experiences of research participation with impaired decision-making capacity require investigation in a greater range of countries and conditions other than dementia, and dissemination through more varied media

Self organising maps for visualising and modelling

The paper describes the motivation of SOMs (Self Organising Maps) and how they are generally more accessible due to the wider available modern, more powerful, cost-effective computers. Their advantages compared to Principal Components Analysis and Partial Least Squares are discussed. These allow application to non-linear data, are not so dependent on least squares solutions, normality of errors and less influenced by outliers. In addition there are a wide variety of intuitive methods for visualisation that allow full use of the map space. Modern problems in analytical chemistry include applications to cultural heritage studies, environmental, metabolomic and biological problems result in complex datasets. Methods for visualising maps are described including best matching units, hit histograms, unified distance matrices and component planes. Supervised SOMs for classification including multifactor data and variable selection are discussed as is their use in Quality Control. The paper is illustrated using four case studies, namely the Near Infrared of food, the thermal analysis of polymers, metabolomic analysis of saliva using NMR, and on-line HPLC for pharmaceutical process monitoring

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Learning materials for the older driver

The Centre for Accident Research and Road Safety - Queensland (CARRS-Q) was commissioned by Queensland Transport to develop a set of integrated learning materials that would assist older drivers in better managing their day-to-day driving. The project resulted from a review of current driver management procedures employed in Queensland, and was to form part of a complete Driver Safety and Education Strategy (Watson et al., 1996). The aims of this project were to: (a) help older drivers become more aware of their driving limitations and the age-related driving problems they may experience; and (b) promote ways in which older drivers can moderate their driving as a result of these age-related changes. Ultimately, the resource should encourage older drivers to both self-monitor their driving ability and to make informed decisions about how best to continue driving in the safest possible way

Distinct evolutionary trajectories of V1R clades across mouse species

Abstract Background Many animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus. We report the extent of gene repertoire turnover and conservation among species and clades, as well as the prevalence of positive selection on gene sequences across the V1R tree. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution. Results We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. We identify putative species-specific gene expansions, including a large clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future study. We find evidence for distinct evolutionary processes across different clades, from largescale turnover to highly conserved repertoires. Patterns of positive selection are similarly variable, as some clades exhibit abundant positive selection while others display high gene sequence conservation. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results reveal clades with receptors detecting female reproductive status are among the most conserved across species, suggesting an important role in V1R chemosensation. Conclusion Analysis of clade-level evolution is critical for understanding species’ chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of receptors