COSMIC: a curated database of somatic variants and clinical data for cancer.

The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.uk/cosmic, is an expert-curated knowledgebase providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies. Within the last 4 years, COSMIC has substantially expanded its utility by adding new resources: the Mutational Signatures catalogue, the Cancer Mutation Census, and Actionability. To improve data accessibility and interoperability, somatic variants have received stable genomic identifiers that are associated with their genomic coordinates in GRCh37 and GRCh38, and new export files with reduced data redundancy have been made available for download.

Choreographing a good death: Carers' experiences and practices of enacting assisted dying.

The proliferation of assisted dying legislative reforms globally is a significant change in the social and medico-legal landscape of end-of-life care. Understanding the impacts of these legislative reforms on family members who care for a dying person is vital, yet under-theorised in research. In this article, drawing on semi-structured interviews with 42 carers for a person who has sought assisted dying in Australia, and extending ideas of ontological choreography we explore the new and complex choreographies enacted by carers in their endeavour to arrange a 'good death' for the dying person. We find that desires to fulfil the dying person's wishes are often accompanied by normative pressures, affective tensions and complexities in bereavement. Enacting assisted dying requires carers to perform a repertoire of highly-staged practices. Yet, institutional obstacles and normative cultural scripts of dying can constrain carer assisted dying practices. Understanding the nuances of carers' experiences and how they navigate this new end-of-life landscape, we argue, provides critical insights about how assisted dying legislation is producing new cultural touchpoints for caring at the end of life. Moreover, we show how emerging cultural scripts of assisted dying are impacting in the lives of these carers.

River basin salinization as a form of aridity.

Soil-salinization affects, to a different extent, more than one-third of terrestrial river basins (estimate based on the Food and Agriculture Organization Harmonized World Soil Database, 2012). Among these, many are endorheic and ephemeral systems already encompassing different degrees of aridity, land degradation, and vulnerability to climate change. The primary effect of salinization is to limit plant water uptake and evapotranspiration, thereby reducing available soil moisture and impairing soil fertility. In this, salinization resembles aridity and-similarly to aridity-may impose significant controls on hydrological partitioning and the strength of land-vegetation-atmosphere interactions at the catchment scale. However, the long-term impacts of salinization on the terrestrial water balance are still largely unquantified. Here, we introduce a modified Budyko's framework explicitly accounting for catchment-scale salinization and species-specific plant salt tolerance. The proposed framework is used to interpret the water-budget data of 237 Australian catchments-29% of which are already severely salt-affected-from the Australian Water Availability Project (AWAP). Our results provide theoretical and experimental evidence that salinization does influence the hydrological partitioning of salt-affected watersheds, imposing significant constraints on water availability and enhancing aridity. The same approach can be applied to estimate salinization level and vegetation salt tolerance at the basin scale, which would be difficult to assess through classical observational techniques. We also demonstrate that plant salt tolerance has a preeminent role in regulating the feedback of vegetation on the soil water budget of salt-affected basins.

Associations of postoperative delirium with activities of daily living in older people after major surgery: A prospective cohort study.

AIMS: To assess the association of postoperative delirium developed in the post-anaesthetic care unit (PACU) with older patients' ability to perform activities of daily living (ADL) during the first five postoperative days. BACKGROUND: Previous studies have focused on the association between postoperative delirium and long-term function decline, however the association between postoperative delirium and the ability to perform ADL, particularly in the immediate postoperative period, needs further investigation. DESIGN: A prospective cohort study. METHODS: A total of 271 older patients who underwent elective or emergency surgery at a tertiary care hospital in Victoria, Australia, participated in the study. Data were collected between July 2021 and December 2021. Delirium was assessed using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The Katz Index of Independence in Activities of Daily Living (KATZ ADL) scale was used to measure ADL. ADL was assessed preoperatively and daily during the first five postoperative days. The STROBE checklist was used to report this study. RESULTS: Results showed that 44 (16.2%) patients developed new episode of delirium. Postoperative delirium was independently associated with decline in ADL (RR = 2.83, 95% CI = 2.71-2.97; p < 0.001). CONCLUSIONS: Postoperative delirium was associated with a decline in ADL among older people during the first five postoperative days. Screening for delirium in the PACU is essential to identify delirium during the early stages of postoperative period and implement a timely comprehensive plan. RELEVANCE TO CLINICAL PRACTICE: Delirium assessment of older patients in the PACU, and for at least the first five postoperative days, is strongly recommended. We also recommend engagement of patients in a focused physical and cognitive daily activity plan, particularly for older patients undergoing major surgery. PATIENT OR PUBLIC CONTRIBUTION: Patients and nurses helped in data collection at a tertiary care hospital.

Evaluation of consultation liaison psychiatry in Australian public hospitals (AU-CLS-1).

OBJECTIVE: This study aimed to determine whether consultation liaison psychiatric service (CLS) staffing within Australian public hospitals meet national and international minimum staffing standards. METHOD: Semi structured interviews were conducted with CLS Directors across Australia from August to December 2021. Data were collected on demographics, staffing, funding, hospital size and admissions. RESULTS: The majority of services did not meet minimum standards for CLS staffing. Non-medical staff outnumbered medical staff with increasing rurality. Psych-oncology CLS had the greatest resources, skill mix and service breadth. CONCLUSION: Although CLS are heterogeneous, most services are inadequately resourced to provide baseline specialist mental health care in Australian hospitals. Establishing national minimum standards for CLS staffing will facilitate uniform service development and quality care provision.

Approximating steady state distributions for household structured epidemic models.

Household-structured infectious disease models consider the increased transmission potential between individuals of the same household when compared with two individuals in different households. Accounting for these heterogeneities in transmission enables control measures to be more effectively planned. Ideally, pre-control data may be used to fit such a household-structured model at an endemic steady state, before making dynamic forward-predictions under different proposed strategies. However, this requires the accurate calculation of the steady states for the full dynamic model. We observe that steady state SIS dynamics with household structure cannot necessarily be described by the master equation for a single household, instead requiring consideration of the full system. However, solving the full system of equations becomes increasingly computationally intensive, particularly for higher-dimensional models. We compare two approximations to the full system: the single household master equation; and a proposed alternative method, using the Fokker-Planck equation. Moment closure is another commonly used method, but for more complicated systems, the equations quickly become unwieldy and very difficult to derive. In comparison, using the master equation for a single household is easily implementable, however it can be quite inaccurate. In this paper we compare these methods in terms of accuracy and ease of implementation. We find that there are regions of parameter space in which each method outperforms the other, and that these regions of parameter space can be characterised by the infection prevalence, or by the correlation between household states.

Predictions of COVID-19 dynamics in the UK: Short-term forecasting and analysis of potential exit strategies.

Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a "stay at home" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. We present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. The model captures a range of age-dependent heterogeneities, reduced transmission from asymptomatic infections and produces a good fit to the key epidemic features over time. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020 on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. We find that significant relaxation of social distancing measures from 7th May onwards can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. Our work confirms the effectiveness of stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. It also provides strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.

Working with palliative care physicians to prepare for voluntary assisted dying legislation.

OBJECTIVE: The Victorian Voluntary Assisted Dying Act 2017 (the Act) exposed a spectrum of opinions regarding euthanasia and physician-assisted suicide amongst Victorian palliative care physicians leading to sometimes acrimonious debate. The profession was unable to articulate a unified role in respect of VAD. METHOD: A collaboration between psychiatry and palliative care led to a series of group discussions in order to prepare for the Act and to re-establish professional cohesion. RESULTS: Although the meetings revealed a plurality of views regarding VAD amongst palliative care physicians, the majority were firmly against the Act. Early meetings revealed strong feelings of shock and an inability to proceed. Previous debates resurfaced between those in support and those not in support of VAD. Over time, there was increased acceptance of the need to adapt to the presence of the Act in order to limit its impact on the robust relationship with the patient central to the practice of palliative care. CONCLUSIONS: The implementation of VAD legislation requires an active process to address the challenges it represents for palliative care physicians. Collaborative facilitated meetings can help re-establish group cohesion through affirming the core principles of palliative care which remain independent of VAD.

An analysis of school absences in England during the COVID-19 pandemic.

BACKGROUND: The introduction of SARS-CoV-2, the virus that causes COVID-19 infection, in the UK in early 2020, resulted in the introduction of several control policies to reduce disease spread. As part of these restrictions, schools were closed to all pupils in March (except for vulnerable and key worker children), before re-opening to certain year groups in June. Finally, all school children returned to the classroom in September. METHODS: Here, we analyse data on school absences in late 2020 as a result of COVID-19 infection and how that varied through time as other measures in the community were introduced. We utilise data from the Department for Education Educational Settings database and examine how pupil and teacher absences change in both primary and secondary schools. RESULTS: Our results show that absences as a result of COVID-19 infection rose steadily following the re-opening of schools in September. Cases in teachers declined during the November lockdown, particularly in regions previously in tier 3, the highest level of control at the time. Cases in secondary school pupils increased for the first 2 weeks of the November lockdown, before decreasing. Since the introduction of the tier system, the number of absences with confirmed infection in primary schools was observed to be (markedly) lower than that in secondary schools. In December, we observed a large rise in the number of absences per school in secondary school settings in the South East and London, but such rises were not observed in other regions or in primary school settings. We conjecture that the increased transmissibility of the new variant in these regions may have contributed to this rise in secondary school cases. Finally, we observe a positive correlation between cases in the community and cases in schools in most regions, with weak evidence suggesting that cases in schools lag behind cases in the surrounding community. CONCLUSIONS: We conclude that there is no significant evidence to suggest that schools are playing a substantial role in driving spread in the community and that careful monitoring may be required as schools re-open to determine the effect associated with open schools upon community incidence.

Palliative care physicians' preparation and planning for the implementation of the Voluntary Assisted Dying Act in Victoria.

BACKGROUND: In November 2017, the Victorian Voluntary Assisted Dying (VAD) Act was passed enabling people with a progressive terminal illness to end their life voluntarily. Heated debate abounded including, to some extent within palliative care, which was also challenged with developing processes around the legislation enactment. AIM: In response, the lead author convened a series of meetings of palliative care physicians to: (i) share ideas about preparations being undertaken within services; and (ii) re-establish professional cohesion following the divide that the legislation had presented. METHODS: A series of three closed meetings were held between the legislation passage and its implementation, with all Victorian palliative care physicians invited to attend. Meetings were facilitated by an experienced psychiatrist from outside the field. RESULTS: These meetings proved very valuable as physicians collectively sought to define and respond to challenges, simultaneously reflecting on the personal and professional implications for individuals and the field. Key areas raised including gauging institutional 'readiness' for the legislation through staff surveys; the educational role of palliative care staff of the legislation implications; communication skills training; the role (if any) of palliative care in the processes of VAD; and the perceptions of palliative care itself in health services and the community. It was during the processes of discussing challenges and sharing solutions that the attendees appeared to reaffirm their professional interconnections. CONCLUSION: A description of the key elements of these discussions may be useful to others who may yet face similar circumstances with the introduction of VAD legislation.

Can depressed patients make a decision to request voluntary assisted dying?

Depressive symptoms, including those as part of a major depressive disorder, are common at the end of life. A number of psychiatrists consider that a diagnosis of major depression precludes the capacity to make a decision to request voluntary assisted dying (VAD), although this is not a unanimous view. This paper uses a case of a patient in which two different psychiatric opinions were formed regarding her capacity to make the decision to request VAD. The difference of view can be related to whether major depression was diagnosed and the association made between depression and the capacity to request VAD. The view that an absence of major depression is required in order to establish the capacity to request VAD is potentially at odds with the legal definition and not necessarily in keeping with the patient's experience at the end of life.

Homeless men with psychosis are spending more time shelterless.

OBJECTIVE: The objective of this study was to determine if homeless men with psychosis in central Melbourne have spent a greater proportion of the past 12 months in homeless settings as compared with the same group 15 years previously. METHOD: A 12-month accommodation history was collected from all men with psychosis assessed by a homeless outreach mental health team over a 12-month period commencing 2018 and compared with data from 2006. RESULTS: Between 2006 and 2018, the percentage of time spent homeless in the previous 12 months rose from 50% to 80% (p = 0.0001). The mean time spent shelterless increased from 72 days to 149 days (p = 0.0001). CONCLUSIONS: The amount of time spent homeless has increased in men with psychosis assessed in central Melbourne. This finding suggests that men with psychosis are becoming increasingly entrenched in homeless settings. Addressing this trend requires an increased emphasis on assertive outreach, greater access to acute inpatient and long-term rehabilitation units, and more low cost affordable housing, including housing first facilities.

Modeling Treatment Strategies to Inform Yaws Eradication.

Yaws is a neglected tropical disease targeted for eradication by 2030. To achieve eradication, finding and treating asymptomatic infections as well as clinical cases is crucial. The proposed plan, the Morges strategy, involves rounds of total community treatment (i.e., treating the whole population) and total targeted treatment (TTT) (i.e., treating clinical cases and contacts). However, modeling and empirical work suggests asymptomatic infections often are not found in the same households as clinical cases, reducing the utility of household-based contact tracing for a TTT strategy. We use a model fitted to data from the Solomon Islands to predict the likelihood of elimination of transmission under different intervention schemes and levels of systematic nontreatment resulting from the intervention. Our results indicate that implementing additional treatment rounds through total community treatment is more effective than conducting additional rounds of treatment of at-risk persons through TTT.

Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease affecting the central nervous system as a result of reactivation of the John Cunningham (JC) polyomavirus and occurs almost exclusively in immunosuppressed individuals. The disease course of PML is variable but usually progressive and often fatal. Treatment is predominantly focused on immune restoration, although this is difficult to do outside of human immunodeficiency virus-associated PML. A recent case series demonstrated a potential role for programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab, to contain and/or clear JC virus. Herein, we discuss the first reported Australian case of a 61-year-old female with PML secondary to chemoimmunotherapy demonstrating complete clearance of JC virus as well as clinical and radiological stabilisation following pembrolizumab treatment.

The impact of increasing general hospital admissions on Consultation-Liaison Psychiatry.

OBJECTIVE: The objective of this study was to identify changes in patients referred to CLP at a typical inner urban teaching hospital over two decades in the context of increased hospital admissions. METHOD: Multivariate analyses were conducted on data collected for all referrals to CLP at Royal Melbourne Hospital between 1998 and 2017. Analyses were conducted with reason for referral, current psychiatric contact, psychiatric diagnosis, discharge destination and follow up as dependent variables, and the year and annual hospital admissions as independent variables. RESULTS: Annual hospital admissions grew at a rate (4.6%), greater than the annual increase in beds (2.0%). Psychosis, suicide attempt, past psychiatric history and behaviour became more common reasons for referral, whilst depression and somatisation became less common. Transfers to and from mental health inpatient units increased. CONCLUSIONS: An increasing proportion of patients seen by CLP have 'acute' problems. Patients with somatisation and depression are seen less frequently. These findings indicate that CLP services need to provide timely assessment and work closely with other elements of the local mental health service in order to optimise patient flow and ensure continuity of care. Local strategies may be required to ensure an adequate breadth of experience for trainees.

Housing First: permanent supported accommodation for people with psychosis who have experienced chronic homelessness.

OBJECTIVES: The objective of this study was to determine whether a 'housing first' permanent supported accommodation was effective in improving housing stability, continuity of care and reducing mental health admissions for persons experiencing chronic homelessness with psychosis. METHODS: A quasi prospective cohort study of 42 chronic homeless persons with psychosis accommodated in a new purpose built facility in central Melbourne. Accommodation stability, mental health service contacts and psychiatric admissions were compared across the 2 years prior, the first 2 years of placement and the 2 years after leaving. RESULTS: The mean number of mental health admissions in the first 2 years of accommodation was less (0.56, SD = 1.0) when compared with in the 2 years prior to accommodation (1.0, SD = 1.4, p = 0.05). There was an increase in the mean total number of days admitted in the 2 years after having left the supported accommodation, (33.3 days, SD = 86.7, p = 0.043) Conclusions: The accommodation of chronic homeless persons with psychosis in a 'housing first' permanent supported accommodation lead to increased housing stability and optimism, improved continuity of care and reduced psychiatric admissions.

A pilot randomized controlled trial of a tailored cognitive behavioural therapy based intervention for depressive symptoms in those newly diagnosed with multiple sclerosis.

BACKGROUND: To examine the effectiveness and acceptability of an 8-week individual tailored cognitive behavioural therapy (CBT) intervention for the treatment of depressive symptoms in those newly diagnosed with multiple sclerosis. METHODS: The current study presents a pilot, parallel group randomized controlled trial (RCT) with an allocation ratio of 1:1 conducted in a large research and teaching hospital in Melbourne, Australia. 30 individuals with a mean age of 36.93 years (SD = 9.63) who were newly diagnosed with multiple sclerosis (MS) (X = 24.87 months, SD = 15.61) were randomized to the CBT intervention (n = 15) or treatment as usual (TAU) (n = 15). The primary outcome was level of depressive symptoms using the Beck Depression Inventory-II (BDI-II). Secondary outcomes were level of anxiety, fatigue and pain impact, sleep quality, coping, acceptance of MS illness, MS related quality of life, social support, and resilience. Tertiary outcomes were acceptability and adherence to the intervention. RESULTS: Large between group treatment effects were found for level of depressive symptoms at post and at 20 weeks follow-up (d = 1.66-1.34). There were also small to large group treatment effects for level of anxiety, fatigue and pain impact, sleep quality, MS related quality of life, resilience, and social support at post and at 20 weeks follow-up (d = 0.17-1.63). There were no drop-outs and participants completed all treatment modules. All participants reported the treatment as 'very useful', and most (73.4%) reported that the intervention had addressed their problems 'completely'. CONCLUSIONS: These data suggest that the tailored early intervention is appropriate and clinically effective for the treatment of depressive symptoms in those newly diagnosed with MS. A larger RCT comparing the CBT intervention with an active comparative treatment with longer term follow-up and cost effectiveness analyses is warranted. The pilot trial has been retrospectively registered on 28/04/2016 with the ISRCTN registry (trial ID ISRCTN10423371).

Persistent disability is a risk factor for late-onset mental disorder after serious injury.

BACKGROUND: Most of what we know about the psychiatric consequences of injury is limited to the first year. Determining the prevalence of and risk factors for psychiatric morbidity beyond one year will aid service development and facilitate timely diagnosis and treatment. The aim of this prognostic study was to determine the prevalence of mental disorders in the three years following serious injury and to identify risk factors for the onset of new disorders after 1 year. METHODS: Of 272 patients assessed in hospital following serious injury, 196 (72.1%) were reassessed at 3 years. Assessment involved gold standard semi-structured interviews for psychiatric diagnoses, risk factors for mental disorder, injury measures and pain scores. RESULTS: More than a quarter of all patients were diagnosed with at least one mood or anxiety disorder at some stage during the three years following their injury. The most common diagnoses were major depression (20.0%), generalised anxiety disorder (6.7%) and panic disorder (6.7%). For a third of these patients, the disorder appeared after 12 months, for which persistent physical disability was an independent risk factor. CONCLUSION: Although there is a necessary focus on the early detection and treatment of mental disorders after injury, attention to later onset disorders is also required for those with persistent pain and physical disability.