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Some of the greatest successes in infectious disease control rest on empirically grounded models of human and livestock infections. In contrast, disease control in wildlife has not always been as successful. Timely translation of knowledge into proposed management actions remains a challenge in several wildlife disease systems, one of which is pneumonia management in bighorn sheep throughout the North American West. Although pneumonia was recognised as a major impediment to bighorn sheep conservation >80 years ago, a series of challenges stymied the management decision-making process. Despite past obstacles, recent advances from long-term, intensive studies of marked individual sheep have motivated new interest in research-driven strategies for disease management in this system. The system provides an unusual opportunity to study an emerging pathogen disproportionately impacting immature animals through infections that originate from asymptomatically infected adult hosts. We tell the story of bighorn sheep pneumonia, emphasising the obstacles that historically hindered decision-making, the biological or logistical constraints underlying each decision point, and the particular empirical insights that clarified each constraint.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.
The short-term impact of prolonged grief disorder (PGD) following bereavement is well documented. The longer term sequelae of PGD however are poorly understood, possibly unrecognized, and may be incorrectly attributed to other mental health disorders and hence undertreated.
The aims of this study were to prospectively evaluate the prevalence of PGD three years post bereavement and to examine the predictors of long-term PGD in a population-based cohort of bereaved cancer caregivers.
A cohort of primary family caregivers of patients admitted to one of three palliative care services in Melbourne, Australia, participated in the study (n = 301). Sociodemographic, mental health, and bereavement-related data were collected from the caregiver upon the patient's admission to palliative care (T1). Further data addressing circumstances around the death and psychological health were collected at six (T2, n = 167), 13 (T3, n = 143), and 37 months (T4, n = 85) after bereavement.
At T4, 5% and 14% of bereaved caregivers met criteria for PGD and subthreshold PGD, respectively. Applying the total PGD score at T4, linear regression analysis found preloss anticipatory grief measured at T1 and self-reported coping measured at T2 were highly statistically significant predictors (both p < 0.0001) of PGD in the longer term.
For almost 20% of caregivers, the symptoms of PGD appear to persist at least three years post bereavement. These findings support the importance of screening caregivers upon the patient's admission to palliative care and at six months after bereavement to ascertain their current mental health. Ideally, caregivers at risk of developing PGD can be identified and treated before PGD becomes entrenched.
As referrals to specialist palliative care (PC) grow in volume and diversity, an evidence-based triage method is needed to enable services to manage waiting lists in a transparent, efficient, and equitable manner. Discrete choice experiments (DCEs) have not to date been used among PC clinicians, but may serve as a rigorous and efficient method to explore and inform the complex decision-making involved in PC triage. This article presents the protocol for a novel application of an international DCE as part of a mixed-method research program, ultimately aiming to develop a clinical decision-making tool for PC triage.
Five stages of protocol development were undertaken: (1) identification of attributes of interest; (2) creation and (3) execution of a pilot DCE; and (4) refinement and (5) planned execution of the final DCE.
Six attributes of interest to PC triage were identified and included in a DCE that was piloted with 10 palliative care practitioners. The pilot was found to be feasible, with an acceptable cognitive burden, but refinements were made, including the creation of an additional attribute to allow independent analysis of concepts involved. Strategies for recruitment, data collection, analysis, and modeling were confirmed for the final planned DCE.
Significance of results
This DCE protocol serves as an example of how the sophisticated DCE methodology can be applied to health services research in PC. Discussion of key elements that improved the utility, integrity, and feasibility of the DCE provide valuable insights.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Provision of bereavement support is an essential component of palliative care service delivery. While bereavement support is integral to palliative care, it is typically insufficiently resourced, under-researched, and not systematically applied. Our aim was to develop bereavement standards to assist palliative care services to provide targeted support to family caregivers.
We employed a multiple-methods design for our study, which included: (1) a literature review, (2) a survey of palliative care service providers in Australia, (3) interviews with national (Australian) and international experts, (4) key stakeholder workshops, and (5) a modified Delphi-type survey.
A total of 10 standards were developed along with a pragmatic care pathway to assist palliative care services with implementation of the standards.
Significance of results:
The bereavement standards and care pathway constitute a key initiative in the evolution of bereavement support provided by palliative care services. Future endeavors should refine and examine the impact of these standards. Additional research is required to enhance systematic approaches to quality bereavement care.
Despite significant needs, patients with chronic obstructive pulmonary disease (COPD) make limited use of palliative care, in part because the current models of palliative care do not address their key concerns.
Our aim was to develop a tailored model of palliative care for patients with COPD and their family caregivers.
Based on information gathered within a program of studies (qualitative research exploring experiences, a cohort study examining service use), an expert advisory committee evaluated and integrated data, developed responses, formulated principles to inform care, and made recommendations for practice. The informing studies were conducted in two Australian states: Victoria and South Australia.
A series of principles underpinning the model were developed, including that it must be: (1) focused on patient and caregiver; (2) equitable, enabling access to components of palliative care for a group with significant needs; (3) accessible; and (4) less resource-intensive than expansion of usual palliative care service delivery. The recommended conceptual model was to have the following features: (a) entry to palliative care occurs routinely triggered by clinical transitions in care; (b) care is embedded in routine ambulatory respiratory care, ensuring that it is regarded as “usual” care by patients and clinicians alike; (c) the tasks include screening for physical and psychological symptoms, social and community support, provision of information, and discussions around goals and preferences for care; and (d) transition to usual palliative care services is facilitated as the patient nears death.
Significance of results:
Our proposed innovative and conceptual model for provision of palliative care requires future formal testing using rigorous mixed-methods approaches to determine if theoretical propositions translate into effectiveness, feasibility, and benefits (including economic benefits). There is reason to consider adaptation of the model for the palliative care of patients with other nonmalignant conditions.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
We previously reported an association between 5HTTLPR genotype and
outcome following cognitive–behavioural therapy (CBT) in child anxiety
(Cohort 1). Children homozygous for the low-expression short-allele
showed more positive outcomes. Other similar studies have produced mixed
results, with most reporting no association between genotype and CBT
To replicate the association between 5HTTLPR and CBT outcome in child
anxiety from the Genes for Treatment study (GxT Cohort 2,
n = 829).
Logistic and linear mixed effects models were used to examine the
relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both
cohorts were performed.
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.
Mega-analyses identified a significant association between 5HTTLPR and
remission from all anxiety disorders at follow-up (odds ratio 0.45,
P = 0.014), but not primary anxiety disorder
The association between 5HTTLPR genotype and CBT outcome did not
replicate. Short-allele homozygotes showed more positive treatment
outcomes, but with small, non-significant effects. Future studies would
benefit from utilising whole genome approaches and large, homogenous
The difficulties in conducting palliative care research have been widely acknowledged. In order to generate the evidence needed to underpin palliative care provision, collaborative research is considered essential. Prior to formalizing the development of a research network for the state of Victoria, Australia, a preliminary study was undertaken to ascertain interest and recommendations for the design of such a collaboration.
Three data-collection strategies were used: a cross-sectional questionnaire, interviews, and workshops. The questionnaire was completed by multidisciplinary palliative care specialists from across the state (n = 61); interviews were conducted with senior clinicians and academics (n = 21) followed by two stakeholder workshops (n = 29). The questionnaire was constructed specifically for this study, measuring involvement of and perceptions of palliative care research.
Both the interview and the questionnaire data demonstrated strong support for a palliative care research network and aided in establishing a research agenda. The stakeholder workshops assisted with strategies for the formation of the Palliative Care Research Network Victoria (PCRNV) and guided the development of the mission and strategic plan.
Significance of results:
The research and efforts to date to establish the PCRNV are encouraging and provide optimism for the evolution of palliative care research in Australia. The international implications are highlighted.
Ensuring a consistent and systematic approach to the delivery of care for people with advanced disease is a priority for palliative care services worldwide. Many clinical tools are available to aid in this process; however, they are often used sporadically, and implementation of a routine set of clinical tools to guide care planning in the specialist palliative care sector in Australia has not been achieved. This study sought to recommend key clinical tools that may assist with the assessment and care planning of specialist palliative care provision for patients and family caregivers admitted to specialist palliative care settings (home, hospital, and hospice).
A mixed-methods sequential approach over four phases was employed, involving: (1) a palliative care sector survey, (2) a systematic literature review, (3) an appraisal of identified clinical tools, and (4) a focus group with an expert panel who critiqued and endorsed a final suite of clinical tools recommended for specialist palliative care.
Twelve tools with practical relevance were recommended for use across settings of care.
Significance of Results:
Palliative services should review current practices and seek to implement this recommended suite of tools to enhance assessment and guide care delivery across care settings. Subsequent evaluation should also occur.
Despite the availability of palliative care in many countries, legalization of euthanasia and physician-assisted suicide (EAS) continues to be debated—particularly around ethical and legal issues—and the surrounding controversy shows no signs of abating. Responding to EAS requests is considered one of the most difficult healthcare responsibilities. In the present paper, we highlight some of the less frequently discussed practical implications for palliative care provision if EAS were to be legalized. Our aim was not to take an explicit anti-EAS stance or expand on findings from systematic reviews or philosophical and ethico-legal treatises, but rather to offer clinical perspectives and the potential pragmatic implications of legalized EAS for palliative care provision, patients and families, healthcare professionals, and the broader community.
We provide insights from our multidisciplinary clinical experience, coupled with those from various jurisdictions where EAS is, or has been, legalized.
We believe that these issues, many of which are encountered at the bedside, must be considered in detail so that the pragmatic implications of EAS can be comprehensively considered.
Significance of Results:
Increased resources and effort must be directed toward training, research, community engagement, and ensuring adequate resourcing for palliative care before further consideration is given to allocating resources for legalizing euthanasia and physician-assisted suicide.