Place of Death for Adults Receiving Specialist Palliative Care in Their Last 3 Months of Life: Factors Associated With Preferred Place, Actual Place, and Place of Death Congruence.

Objectives: Congruence between the preferred and actual place of death is recognised as an important quality indicator in end-of-life care. However, there may be complexities about preferences that are ignored in summary congruence measures. This article examined factors associated with preferred place of death, actual place of death, and congruence for a sample of patients who had received specialist palliative care in the last three months of life in Ireland. Methods: This article analysed merged data from two previously published mortality follow-back surveys: Economic Evaluation of Palliative Care in Ireland (EEPCI); Irish component of International Access, Rights and Empowerment (IARE I). Logistic regression models examined factors associated with (a) preferences for home death versus institutional setting, (b) home death versus hospital death, and (c) congruent versus non-congruent death. Setting: Four regions with differing levels of specialist palliative care development in Ireland. Participants: Mean age 77, 50% female/male, 19% living alone, 64% main diagnosis cancer. Data collected 2011-2015, regression model sample sizes: n = 342-351. Results: Congruence between preferred and actual place of death in the raw merged dataset was 51%. Patients living alone were significantly less likely to prefer home versus institution death (OR 0.389, 95%CI 0.157-0.961), less likely to die at home (OR 0.383, 95%CI 0.274-0.536), but had no significant association with congruence. Conclusions: The findings highlight the value in examining place of death preferences as well as congruence, because preferences may be influenced by what is feasible rather than what patients would like. The analyses also underline the importance of well-resourced community-based supports, including homecare, facilitating hospital discharge, and management of complex (eg, non-cancer) conditions, to facilitate patients to die in their preferred place.

Primary data on symptom burden and quality of life among elderly patients at risk of dying during unplanned admissions to an NHS hospital: a cohort study using EuroQoL and the integrated palliative care outcome scale.

BACKGROUND: Older people account heavily for palliative care needs at the population level and are growing in number as the population ages. There is relatively little high-quality data on symptom burden and quality of life, since these data are not routinely collected, and this group are under-recruited in primary research. It is unclear which measurement tools are best suited to capture burdens and experience. METHODS: We recruited a cohort of 221 patients aged 75 + years with poor prognosis who had an unplanned admission via the emergency department in a large urban hospital in England between 2019 and 2020. Risk of dying was assessed using the CriSTAL tool. We collected primary data and combined these with routine health records. Baseline clinical data and patient reported quality of life outcomes were collected on admission and reassessed within the first 72 h of presentation using two established tools: EQ-5D-5 L, EQ-VAS and the Integrated Palliative Outcomes Scale (IPOS). RESULTS: Completion rate was 68% (n = 151) and 33.1% were known to have died during admission or within 6 months post-discharge. The vast majority (84.8%) reported severe difficulties with at least one dimension of EQ-5D-5 L at baseline and improvements in EQ-VAS observed at reassessment in 51.7%. The baseline IPOS revealed 78.2% of patients rating seven or more items as moderate, severe or overwhelming, but a significant reduction (-3.6, p < 0.001) in overall physical symptom severity and prevalence was also apparent. No significant differences were noted in emotional symptoms or changes in communication/practical issues. IPOS total score at follow up was positively associated with age, having comorbidities (Charlson index score > = 1) and negatively associated with baseline IPOS and CriSTAL scores. CONCLUSION: Older people with poor prognosis admitted to hospital have very high symptom burden compared to population norms, though some improvement following assessment was observed on all measures. These data provide valuable descriptive information on quality of life among a priority population in practice and policy and can be used in future research to identify suitable interventions and model their effects.

Formal health care costs among older people in Ireland: methods and estimates using The Irish Longitudinal Study on Ageing (TILDA).

Background: Reliable data on health care costs in Ireland are essential to support planning and evaluation of services. New unit costs and high-quality utilisation data offer the opportunity to estimate individual-level costs for research and policy. Methods: Our main dataset was The Irish Longitudinal Study on Ageing (TILDA). We used participant interviews with those aged 55+ years in Wave 5 (2018) and all end-of-life interviews (EOLI) to February 2020. We weighted observations by age, sex and last year of life at the population level. We estimated total formal health care costs by combining reported usage in TILDA with unit costs (non-acute care) and public payer reimbursement data (acute hospital admissions, medications). All costs were adjusted for inflation to 2022, the year of analysis. We examined distribution of estimates across the population, and the composition of costs across categories of care, using descriptive statistics. We identified factors associated with total costs using generalised linear models. Results: There were 5,105 Wave 5 observations, equivalent at the population level to 1,207,660 people aged 55+ years and not in the last year of life, and 763 EOLI observations, equivalent to 28,466 people aged 55+ years in the last year of life. Mean formal health care costs in the weighted sample were EUR 8,053; EUR 6,624 not in the last year of life and EUR 68,654 in the last year of life. Overall, 90% of health care costs were accounted for by 20% of users. Multiple functional limitations and proximity to death were the largest predictors of costs. Other factors that were associated with outcome included educational attainment, entitlements to subsidised care and serious chronic diseases. Conclusions: Understanding the patterns of costs, and the factors associated with very high costs for some individuals, can inform efforts to improve patient experiences and optimise resource allocation.

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.

Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth. Deletion of the IL-22 receptor on cancer cells decreases metastasis to a degree similar to that seen in IL-22-deficient mice. IL-22 induced high expression of CD155, which bound to the activating receptor CD226 on NK cells. Excessive activation led to decreased amounts of CD226 and functionally impaired NK cells, which elevated the metastatic burden. IL-22 signaling was also associated with CD155 expression in human datasets and with poor patient outcomes. Taken together, our findings reveal an immunosuppressive circuit activated by T cell-derived IL-22 that promotes lung metastasis.

Effectiveness and cost-effectiveness of palliative care in natural experiments: a systematic review.

CONTEXT: Investigators in palliative care rely heavily on routinely collected data, which carry risk of unobserved confounding and selection bias. 'Natural experiments' offer opportunities to generate credible causal treatment effect estimates from observational data. OBJECTIVES: We aimed first to review studies that employed 'natural experiments' to evaluate palliative care, and second to consider implications for expanding use of these methods. METHODS: We searched systematically seven databases to identify studies using 'natural experiments' to evaluate palliative care's effect on outcomes and costs. We searched three grey literature repositories, and hand-searched journals and prior systematic reviews. We assessed reporting using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a bespoke methodological quality tool, using two reviewers at each stage. We combined results in a narrative synthesis. RESULTS: We included 17 studies, which evaluated a wide range of interventions and populations. Seven studies employed a difference-in-differences design; five each used instrumental variables and interrupted time series analysis. Outcomes of interest related mostly to healthcare use. Reporting quality was variable. Most studies reported lower costs and improved outcomes associated with palliative care, but a third of utilisation and place of death evaluations found no effect. CONCLUSION: Among the large number of observational studies in palliative care, a small minority have employed causal mechanisms. High-volume routine data collection, the expansion of palliative care services worldwide and recent methodological advances offer potential for increased use of 'natural experiments'. Such studies would improve the quality of the evidence base.

Overprescribing among older people near end of life in Ireland: Evidence of prevalence and determinants from The Irish Longitudinal Study on Ageing (TILDA).

International evidence shows that people approaching end of life (EOL) have high prevalence of polypharmacy, including overprescribing. Overprescribing may have adverse side effects for mental and physical health and represents wasteful spending. Little is known about prescribing near EOL in Ireland. We aimed to describe the prevalence of two undesirable outcomes, and to identify factors associated with these outcomes: potentially questionable prescribing, and potentially inadequate prescribing, in the last year of life (LYOL). We used The Irish Longitudinal Study on Ageing, a biennial nationally representative dataset on people aged 50+ in Ireland. We analysed a sub-sample of participants with high mortality risk and categorised their self-reported medication use as potentially questionable or potentially inadequate based on previous research. We identified mortality through the national death registry (died in <365 days versus not). We used descriptive statistics to quantify prevalence of our outcomes, and we used multivariable logistic regression to identify factors associated with these outcomes. Of 525 observations, 401 (76%) had potentially inadequate and 294 (56%) potentially questionable medications. Of the 401 participants with potentially inadequate medications, 42 were in their LYOL. OF the 294 participants with potentially questionable medications, 26 were in their LYOL. One factor was significantly associated with potentially inadequate medications in LYOL: male (odds ratio (OR) 4.40, p = .004) Three factors were associated with potentially questionable medications in LYOL: male (OR 3.37, p = .002); three or more activities of daily living (ADLs) (OR 3.97, p = .003); and outpatient hospital visits (OR 1.03, p = .02). Thousands of older people die annually in Ireland with potentially inappropriate or questionable prescribing patterns. Gender differences for these outcomes are very large. Further work is needed to identify and reduce overprescribing near EOL in Ireland, particularly among men.

Projecting future health and service use among older people in Ireland: an overview of a dynamic microsimulation model in The Irish Longitudinal Study on Ageing (TILDA).

Background: Demographic ageing is a population health success story but poses unprecedented policy challenges in the 21st century. Policymakers must prepare health systems, economies and societies for these challenges. Policy choices can be usefully informed by models that evaluate outcomes and trade-offs in advance under different scenarios. Methods: We developed a dynamic demographic-economic microsimulation model for the population aged 50 and over in Ireland: the Irish Future Older Adults Model (IFOAM).  Our principal dataset was The Irish Longitudinal Study on Ageing (TILDA). We employed first-order Markovian competing risks models to estimate transition probabilities of TILDA participants to different outcomes: diagnosis of serious diseases, functional limitations, risk-modifying behaviours, health care use and mortality. We combined transition probabilities with the characteristics of the stock population to estimate biennial changes in outcome state.   Results: IFOAM projections estimated large annual increases in total deaths, in the number of people living and dying with serious illness and functional impairment, and in demand for hospital care between 2018 and 2040.  The most important driver of these increases is the rising absolute number of older people in Ireland as the population ages. The increasing proportion of older old and oldest old citizens is projected to increase the average prevalence of chronic conditions and functional limitations. We deemed internal validity to be good but lacked external benchmarks for validation and corroboration of most outcomes. Conclusion: We have developed and validated a microsimulation model that projects health and related outcomes among older people in Ireland.  Future research should address identified policy questions. The model enhances the capacity of researchers and policymakers to quantitatively forecast health and economic dynamics among older people in Ireland, to evaluate ex ante policy responses to these dynamics, and to collaborate internationally on global challenges associated with demographic ageing.

Association Between Hospice Enrollment and Total Health Care Costs for Insurers and Families, 2002-2018.

Importance: Use of hospice has been demonstrated to be cost saving to the Medicare program and yet the extent to which hospice saves money across all payers, including whether it shifts costs to families, is unknown. Objective: To estimate the association between hospice use and total health care costs including family out-of-pocket health care spending. Design Setting and Participants: This retrospective cohort study of health care spending in the last 6 months of life used data from the nationally representative Medicare Current Beneficiary Survey (MCBS) between the years 2002 and 2018. Participants were MCBS participants who resided in the community and died between 2002 and 2018. Exposures: Covariate balancing propensity scores were used to compare participants who used hospice (n = 2113) and those who did not (n = 3351), stratified by duration of hospice use. Main Outcomes and Measures: Total health care expenditures were measured across payers (family out-of-pocket, Medicare, Medicare Advantage, Medicaid, private insurance, private health maintenance organizations, Veteran's Administration, and other) and by expenditure type (inpatient care, outpatient care, medical visits, skilled nursing, home health, hospice, durable medical equipment, and prescription drugs). Results: The study population included 5464 decedents (mean age 78.7 years; 48% female) and 38% enrolled with hospice. Total health care expenditures were lower for those who used hospice compared with propensity score weighted non-hospice control participants for the last 3 days of life ($2813 lower; 95% CI, $2396-$3230); last week of life ($6806 lower; 95% CI, $6261-$7350); last 2 weeks of life ($8785 lower; 95% CI, $7971-$9600); last month of life ($11 747 lower; 95% CI, $10 072-$13 422); and last 3 months of life ($10 908 lower; 95% CI, $7283-$14 533). Family out-of-pocket expenditures were lower for hospice enrollees in the last 3 days of life ($71; 95% CI, $43-$100); last week of life ($216; 95% CI, $175-$256); last 2 weeks of life ($265; 95% CI, $149-$382); and last month of life ($670; 95% CI, $530-$811) compared with those who did not use hospice. Health care savings were associated with reductions in inpatient care. Conclusions and Relevance: In this population-based cohort study of community-dwelling Medicare beneficiaries, hospice enrollment was associated with lower total health care costs for the last 3 days to 3 months of life. Importantly, we found no evidence of cost shifting from Medicare to families related to hospice enrollment. The magnitude of lower out-of-pocket spending to families who enrolled with hospice is meaningful to many Americans, particularly those with lower socioeconomic status.

Chemical evidence for the tradeoff-in-the-nephron hypothesis to explain secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) complicates advanced chronic kidney disease (CKD) and causes skeletal and other morbidity. In animal models of CKD, SHPT was prevented and reversed by reduction of dietary phosphate in proportion to GFR, but the phenomena underlying these observations are not understood. The tradeoff-in-the-nephron hypothesis states that as GFR falls, the phosphate concentration in the distal convoluted tubule ([P]DCT]) rises, reduces the ionized calcium concentration in that segment ([Ca++]DCT), and thereby induces increased secretion of parathyroid hormone (PTH) to maintain normal calcium reabsorption. In patients with CKD, we previously documented correlations between [PTH] and phosphate excreted per volume of filtrate (EP/Ccr), a surrogate for [P]DCT. In the present investigation, we estimated [P]DCT from physiologic considerations and measurements of phosphaturia, and sought evidence for a specific chemical phenomenon by which increased [P]DCT could lower [Ca++]DCT and raise [PTH]. METHODS AND FINDINGS: We studied 28 patients ("CKD") with eGFR of 14-49 mL/min/1.73m2 (mean 29.9 ± 9.5) and 27 controls ("CTRL") with eGFR > 60 mL/min/1.73m2 (mean 86.2 ± 10.2). In each subject, total [Ca]DCT and [P]DCT were deduced from relevant laboratory data. The Joint Expert Speciation System (JESS) was used to calculate [Ca++]DCT and concentrations of related chemical species under the assumption that a solid phase of amorphous calcium phosphate (Ca3(PO4)2 (am., s.)) could precipitate. Regressions of [PTH] on eGFR, [P]DCT, and [Ca++]DCT were then examined. At filtrate pH of 6.8 and 7.0, [P]DCT was found to be the sole determinant of [Ca++]DCT, and precipitation of Ca3(PO4)2 (am., s.) appeared to mediate this result. At pH 6.6, total [Ca]DCT was the principal determinant of [Ca++]DCT, [P]DCT was a minor determinant, and precipitation of Ca3(PO4)2 (am., s.) was predicted in no CKD and five CTRL. In CKD, at all three pH values, [PTH] varied directly with [P]DCT and inversely with [Ca++]DCT, and a reduced [Ca++]DCT was identified at which [PTH] rose unequivocally. Relationships of [PTH] to [Ca++]DCT and to eGFR resembled each other closely. CONCLUSIONS: As [P]DCT increases, chemical speciation calculations predict reduction of [Ca++]DCT through precipitation of Ca3(PO4)2 (am., s.). [PTH] appears to rise unequivocally if [Ca++]DCT falls sufficiently. These results support the tradeoff-in-the-nephron hypothesis, and they explain why proportional phosphate restriction prevented and reversed SHPT in experimental CKD. Whether equally stringent treatment can be as efficacious in humans warrants investigation.

Do Mini-Mental State Examination and Montreal Cognitive Assessment predict high-cost health care users? A competing risks analysis in The Irish Longitudinal Study on Ageing.

OBJECTIVES: Policymakers want to better identify in advance the 10% of people who account for approximately 75% of health care costs. We evaluated how well Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) predicted high costs in Ireland. METHODS/DESIGN: We used five waves from The Irish Longitudinal Study on Ageing, a biennial population-representative survey of people aged 50+ (2010-2018). We used competing risks analysis where our outcome of interest was "high costs" (top 10% at any wave) and the competing outcome was dying or loss to follow-up without first having the high-cost outcome. Our binary predictors of interest were a 'low score' (bottom 10% in the sample) in MMSE (≤25 pts) and MoCA (≤19 pts) at baseline, and we calculated sub-hazard ratios after controlling for sociodemographic, clinical and functional factors. RESULTS: Of 5856 participants, 1427 (24%) had the 'high cost' outcome; 1463 (25%) had a competing outcome; and 2966 (51%) completed eight years of follow-up without either outcome. In multivariable regressions a low MoCA score was associated with high costs (SHR: 1.38 (95% CI: 1.2-1.6) but a low MMSE score was not. Low MoCA score at baseline had a higher true positive rate (40%) than did low MMSE score (35%). The scores had similar association with exit from the study. CONCLUSIONS: MoCA had superior predictive accuracy for high costs than MMSE but the two scores identify somewhat different types of high-cost user. Combining the approaches may improve efforts to identify in advance high-cost users.

Predicting mortality in The Irish Longitudinal Study on Ageing (TILDA): development of a four-year index and comparison with international measures.

OBJECTIVES: We aimed to replicate existing international (US and UK) mortality indices using Irish data. We developed and validated a four-year mortality index for adults aged 50 + in Ireland and compared performance with these international indices. We then extended this model by including additional predictors (self-report and healthcare utilization) and compared its performance to our replication model. METHODS: Eight thousand one hundred seventy-four participants in The Irish Longitudinal Study on Ageing were split for development (n = 4,121) and validation (n = 4,053). Six baseline predictor categories were examined (67 variables total): demographics; cardiovascular-related illness; non-cardiovascular illness; health and lifestyle variables; functional variables; self-report (wellbeing and social connectedness) and healthcare utilization. We identified variables independently associated with four-year mortality in the development cohort and attached these variables a weight according to strength of association. We summed the weights to calculate a single index score for each participant and evaluated predicted accuracy in the validation cohort. RESULTS: Our final 14-predictor (extended) model assigned risk points for: male (1pt); age (65-69: 2pts; 70-74: 4 pts; 75-79: 4pts; 80-84: 6pts; 85 + : 7pts); heart attack (1pt); cancer (3pts); smoked past age 30 (2pts); difficulty walking 100 m (2pts); difficulty using the toilet (3pts); difficulty lifting 10lbs (1pts); poor self-reported health (1pt); and hospital admission in previous year (1pt). Index discrimination was strong (ROC area = 0.78). DISCUSSION: Our index is predictive of four-year mortality in community-dwelling older Irish adults. Comparisons with the international indices show that our 12-predictor (replication) model performed well and suggests that generalisability is high. Our 14-predictor (extended) model showed modest improvements compared to the 12-predictor model.

Public health insurance and mortality in the older population: Evidence from the Irish Longitudinal Study on Ageing.

Most developed countries provide publicly-financed insurance for many health services for their populations although there is considerable variation across countries in the types of services covered, eligible population groups and whether co-payments are levied. The Irish healthcare system, with a complex mix of public and private financing of healthcare services, offers a useful case study for an examination of the impact of type of health insurance cover on population health. In this paper, we investigate the extent to which type of health insurance cover is associated with all-cause, cause-specific, and amenable mortality using data on a representative survey of the population aged 50+ from the Irish Longitudinal Study on Ageing (TILDA) matched to administrative data on death registrations. The results show that those without public or private health insurance have a higher risk of all-cause and cancer mortality. However, there is no evidence that type of health insurance cover affects mortality risk from causes that are considered amenable to healthcare intervention, although this analysis was based on a much smaller sample size. This analysis provides important evidence for a country that is implementing reforms to its financing and delivery structures in order to move towards a system of universal healthcare.

Out-of-pocket costs near end of life in low- and middle-income countries: A systematic review.

BACKGROUND: Globally, there is a rise in chronic disease, including cancer, major organ failure and dementias. Patients and their families in low- and middle-income countries (LMICs) pay a high proportion of medical costs out of pocket (OOP), and a diagnosis of serious illness often has catastrophic financial consequences. We therefore conducted a review of the literature to establish what is known about OOP costs near end of life in LMICs. AIMS: To identify, organise and report the evidence on out-of-pocket costs in adult end-of-life populations in LMIC. METHODS: A systematic search of 8 databases and a hand search of relevant systematic reviews and grey literature was performed. Two independent reviewers screened titles and abstracts, assessed papers for eligibility and extracted data. The review was registered with PROSPERO and adhered to the Preferred Reporting items for Systematic Reviews and Meta Analyses. The Mixed Methods Appraisal Tool was used to assess quality. The Wagstaff taxonomy was used to describe OOP. RESULTS: After deduplication, 9,343 studies were screened, of which 51 were read and rejected as full texts, and 12 were included in the final review. OOP costs increased with advanced illness and disease severity. The main drivers of OOP were medications and hospitalizations, with high but variable percentages of the affected populations reporting financial catastrophe, lost income, foregone education and other pressures. CONCLUSION: Despite a small number of included studies and heterogeneity in methodology and reporting, it is clear that OOP costs for care near end of life in LMIC represent an important source of catastrophic health expenditures and impoverishment. This suggests a role for widespread, targeted efforts to avoid poverty traps. Financial protection policies for those suffering from incurable disease and future research on the macro- and micro- economics of palliative care delivery in LMIC are greatly needed.

[Considerations for quality assurance of discussions with relatives in direct association with organ donation]. / Überlegungen für eine Qualitätssicherung der Angehörigengespräche in einem unmittelbaren Zusammenhang mit einer Organspende.

BACKGROUND: Discussions with relatives are relevant and crucial aspects of the organ donation process and contribute to a consolidated and sustainable decision by the families of the deceased. Despite the great importance of family care, there is no systematic analysis of the quality of this communication, in contrast to the diagnosis of irreversible loss of brain function, organ retrieval and organ transplantation. For this reason, organ donation experts were interviewed about recurring characteristics of communication with relatives of the deceased. The aim of this qualitative study was to define criteria for the assessment of the structure and quality of the communication process with relatives for internal quality management in Germany. METHODS: Based on a systematic literature review and with the help of the 5­stage S2PS2 (system for creating a questionnaire) procedure according to Kruse, interview guidelines were initially developed. As a second step, in guideline-based interviews 10 experienced organ donation experts were questioned about structural, procedural and ethical aspects of their discussions with relatives. Following the interviews, a software-based qualitative content analysis was carried out with a combined inductive-deductive category system. Finally, the first quality assurance measures for the interviews with relatives were developed in a multistep process, closely following the methodological principles V1.1 of the Institute for Quality Assurance and Transparency in Health Care (IQTIG). The individual research steps were accompanied by an expert group consisting of physicians, nurses, theologians and ethicists utilizing an anonymous Delphi procedure. RESULTS: In the qualitative content analysis, 5 main categories with 30 subcategories on quality relevant aspects could be identified (including, standardization and technique of conversation, interview framework and context factors, professional expertise of the interviewers, wishes of the organ donation experts). On this basis, 6 criteria for the structural quality and 7 criteria for the process quality of the discussions with relatives were formulated and summarized in a respective quality bundle. These criteria address, among other things, interprofessional communication, structured training concepts, regular further training of all team members, use of standardized communication and counselling strategies as well as documented preliminary meetings and debriefings, including supervising elements. They emphasize interdisciplinary professionalism and process management in a protected environment as well as quality assured communication and documentation. Recommendations were made for expanding the existing documentation for the organ donation process and for documenting the preliminary meetings and debriefings. CONCLUSION: Recurring communication and process characteristics as well as requirements for the members of the treatment team who conduct the conversation can be identified for the interviews with relatives, which show potential for improvement to various degrees. This justifies the structured derivation of a quality bundle for the structural and process quality family care related to organ donation, which should enable a low-threshold entry into an institution internal systematic quality assessment of communication with relatives in Germany. Due to the different legal, medical and social specifics in an international context, the study results cannot be directly transferred to other countries.

Advance Identification of Patients With Chronic Conditions and Acute Respiratory Failure at Greatest Risk for High-Intensity, Costly Care.

CONTEXT: Patients with underlying chronic illness requiring mechanical ventilation for acute respiratory failure are at risk for poor outcomes and high costs. OBJECTIVES: Identify characteristics at time of intensive care unit (ICU) admission that identify patients at highest risk for high-intensity, costly care. METHODS: Retrospective cohort study using electronic health and financial records (2011-2017) for patients requiring ≥48 hours of mechanical ventilation with ≥1 underlying chronic condition at an academic healthcare system. Main outcome was total cost of index hospitalization. Exposures of interest included number and type of chronic conditions. We used finite mixture models to identify the highest-cost group. RESULTS: 4,892 patients met study criteria. Median cost for index hospitalization was $135,238 (range, $9,748 -$3,176,065). Finite mixture modelling identified three classes with mean costs of $89,980, $150,603, and $277,712. Patients more likely to be in the high-cost class were: 1) < 72 years old (OR: 2.03; 95% CI:1.63, 2.52); 2) with dementia (OR: 1.55; 95% CI:1.17, 2.06) or chronic renal failure (OR: 1.27; 95% CI:1.08, 1.48); 3) weight loss ≥ 5% in year prior to hospital admission (OR: 1.25; 95% CI:1.05, 1.48); and 4) hospitalized during prior year (OR: 1.92; 95% CI:1.58, 2.35). CONCLUSION: Among patients with underlying chronic illness and acute respiratory failure, we identified characteristics associated with the highest costs of care. Identifying these patients may be of interest to healthcare systems and hospitals and serve as one indication to invest resources in palliative and supportive care programs that ensure this care is consistent with patients' goals.

Effectiveness of a nurse-delivered (FOCUS+) and a web-based (iFOCUS) psychoeducational intervention for people with advanced cancer and their family caregivers (DIAdIC): study protocol for an international randomized controlled trial.

BACKGROUND: Worldwide, millions of people with advanced cancer and their family caregivers are experiencing physical and psychological distress. Psychosocial support and education can reduce distress and prevent avoidable healthcare resource use. To date, we lack knowledge from large-scale studies on which interventions generate positive outcomes for people with cancer and their informal caregivers' quality of life. This protocol describes the DIAdIC study that will evaluate the effectiveness of two psychosocial and educational interventions aimed at improving patient-family caregiver dyads' emotional functioning and self-efficacy. METHODS: We will conduct an international multicenter three-arm randomized controlled trial in Belgium, Denmark, Ireland, Italy, The Netherlands, and the United Kingdom. In each country, 156 dyads (936 in total) of people with advanced cancer and their family caregiver will be randomized to one of the study arms: 1) a nurse-led face-to-face intervention (FOCUS+), 2) a web-based intervention (iFOCUS) or 3) a control group (care as usual). The two interventions offer tailored psychoeducational support for patient-family caregiver dyads. The nurse-led face-to-face intervention consists of two home visits and one online video session and the web-based intervention is completed independently by the patient-family caregiver dyad in four online sessions. The interventions are based on the FOCUS intervention, developed in the USA, that addresses five core components: family involvement, optimistic outlook, coping effectiveness, uncertainty reduction, and symptom management. The FOCUS intervention will be adapted to the European context. The primary outcomes are emotional functioning and self-efficacy of the patient and the family caregiver, respectively. The secondary outcomes are quality of life, benefits of illness, coping, dyadic communication, and ways of giving support of the patient and family caregiver. DISCUSSION: DIAdIC aims to develop cost-effective interventions that integrate principles of early palliative care into standard care. The cross-country setup in six European countries allows for comparison of effectiveness of the interventions in different healthcare systems across Europe. By focusing on empowerment of the person with cancer and their family caregiver, the results of this RCT can contribute to the search for cost-effective novel interventions that can relieve constraints on professional healthcare. TRIAL REGISTRATION: Registration on ClinicalTrials.gov on 12/11/2020, identifier NCT04626349 . DATE AND VERSION IDENTIFIER: 20211209_DIAdIC_Protocol_Article.

Surgery versus conservative management of stable thoracolumbar fracture: the PRESTO feasibility RCT.

BACKGROUND: There is informal consensus that simple compression fractures of the body of the thoracolumbar vertebrae between the 10th thoracic vertebra and the second lumbar vertebra without neurological complications can be managed conservatively and that obvious unstable fractures require surgical fixation. However, there is a zone of uncertainty about whether surgical or conservative management is best for stable fractures. OBJECTIVES: To assess the feasibility of a definitive randomised controlled trial comparing surgical fixation with initial conservative management of stable thoracolumbar fractures without spinal cord injury. DESIGN: External randomised feasibility study, qualitative study and national survey. SETTING: Three NHS hospitals. METHODS: A feasibility randomised controlled trial using block randomisation, stratified by centre and type of injury (high- or low-energy trauma) to allocate participants 1 : 1 to surgery or conservative treatment; a costing analysis; a national survey of spine surgeons; and a qualitative study with clinicians, recruiting staff and patients. PARTICIPANTS: Adults aged ≥ 16 years with a high- or low-energy fracture of the body of a thoracolumbar vertebra between the 10th thoracic vertebra and the second lumbar vertebra, confirmed by radiography, computerised tomography or magnetic resonance imaging, with at least one of the following: kyphotic angle > 20° on weight-bearing radiographs or > 15° on a supine radiograph or on computerised tomography; reduction in vertebral body height of 25%; a fracture line propagating through the posterior wall of the vertebra; involvement of two contiguous vertebrae; or injury to the posterior longitudinal ligament or annulus in addition to the body fracture. INTERVENTIONS: Surgical fixation: open spinal surgery (with or without spinal fusion) or minimally invasive stabilisation surgery. Conservative management: mobilisation with or without a brace. MAIN OUTCOME MEASURE: Recruitment rate (proportion of eligible participants randomised). RESULTS: Twelve patients were randomised (surgery, n = 8; conservative, n = 4). The proportion of eligible patients recruited was 0.43 (95% confidence interval 0.24 to 0.63) over a combined total of 30.7 recruitment months. Of 211 patients screened, 28 (13.3%) fulfilled the eligibility criteria. Patients in the qualitative study (n = 5) expressed strong preferences for surgical treatment, and identified provision of information about treatment and recovery and when and how they are approached for consent as important. Nineteen surgeons and site staff participated in the qualitative study. Key themes were the lack of clinical consensus regarding the implementation of the eligibility criteria in practice and what constitutes a stable fracture, alongside lack of equipoise regarding treatment. Based on the feasibility study eligibility criteria, 77% (50/65) and 70% (46/66) of surgeons participating in the survey were willing to randomise for high- and low-energy fractures, respectively. LIMITATIONS: Owing to the small number of participants, there is substantial uncertainty around the recruitment rate. CONCLUSIONS: A definitive trial is unlikely to be feasible currently, mainly because of the small number of patients meeting the eligibility criteria. The recruitment and follow-up rates were slightly lower than anticipated; however, there is room to increase these based on information gathered and the support within the surgical community for a future trial. FUTURE WORK: Development of consensus regarding the population of interest for a trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12094890. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 62. See the NIHR Journals Library website for further project information.

Fractures occurring in the mid- to low back region (or thoracolumbar fractures) are the most common back fractures. When the fracture is stable with no spinal nerve injury, there is uncertainty whether treatment with surgery or non-surgical treatment (e.g. stabilising the spine with a brace) results in the best outcome for patients. The Pragmatic Randomised Evaluation of Stable Thoracolumbar fracture treatment Outcomes (PRESTO) study aimed to explore whether or not it would be feasible to carry out a full-scale study to find out which of these two treatments works best. Adults aged ≥ 16 years being treated for these fractures in three hospitals were invited to take part in the study. Over the course of 1 year, we assessed how many patients were treated, the number who met the study entry criteria and the proportion of eligible patients who agreed to take part. Staff and patients were interviewed about the study processes and their experiences of taking part. Spine surgeons from around the UK were also asked to complete an online survey, which asked questions about the treatment of patients with this fracture. There were fewer patients than expected who met the study entry criteria and, of these, fewer patients who agreed to take part. There were differences among surgeons about the definition of a stable fracture, and we found that surgeons have strong views about whether or not surgery is appropriate when fractures are stable. We also found that more support would be required for the staff involved in inviting patients to take part in a bigger study, and that the format and content of information provided to patients needs to be improved. The findings of the PRESTO study showed that a large trial is unlikely to be successful at this time; however, we have provided important information for future research into the treatment of these fractures.

Using predicted length of stay to define treatment and model costs in hospitalized adults with serious illness: an evaluation of palliative care.

BACKGROUND: Economic research on hospital palliative care faces major challenges. Observational studies using routine data encounter difficulties because treatment timing is not under investigator control and unobserved patient complexity is endemic. An individual's predicted LOS at admission offers potential advantages in this context. METHODS: We conducted a retrospective cohort study on adults admitted to a large cancer center in the United States between 2009 and 2015. We defined a derivation sample to estimate predicted LOS using baseline factors (N = 16,425) and an analytic sample for our primary analyses (N = 2674) based on diagnosis of a terminal illness and high risk of hospital mortality. We modelled our treatment variable according to the timing of first palliative care interaction as a function of predicted LOS, and we employed predicted LOS as an additional covariate in regression as a proxy for complexity alongside diagnosis and comorbidity index. We evaluated models based on predictive accuracy in and out of sample, on Akaike and Bayesian Information Criteria, and precision of treatment effect estimate. RESULTS: Our approach using an additional covariate yielded major improvement in model accuracy: R2 increased from 0.14 to 0.23, and model performance also improved on predictive accuracy and information criteria. Treatment effect estimates and conclusions were unaffected. Our approach with respect to treatment variable yielded no substantial improvements in model performance, but post hoc analyses show an association between treatment effect estimate and estimated LOS at baseline. CONCLUSION: Allocation of scarce palliative care capacity and value-based reimbursement models should take into consideration when and for whom the intervention has the largest impact on treatment choices. An individual's predicted LOS at baseline is useful in this context for accurately predicting costs, and potentially has further benefits in modelling treatment effects.