Characteristics of patients diagnosed with pancreatic cancer who access palliative care: An observational study.

PURPOSE: Despite the benefits of palliative care (PC) in pancreatic cancer, little is known about patients who access PC. This observational study examines the characteristics of patients with pancreatic cancer at their first episode of PC. METHODS: First-time, specialist PC episodes captured through the Palliative Care Outcomes Collaboration (PCOC), in Victoria, Australia between 2014 and 2020, for pancreatic cancer, were identified. Multivariable logistic regression analyses examined the impact of patient- and service-level characteristics on symptom burden (measured through patient-reported outcome measures and clinician-rated scores) at first PC episode. RESULTS: Of 2890 eligible episodes, 45% began when the patient was deteriorating and 32% ended in death. High fatigue and appetite-related distress were most common. Generally, increasing age, higher performance status and more recent year of diagnosis predicted lower symptom burden. No significant differences were noted between symptom burden of regional/remote versus major city dwellers; however, only 11% of episodes recorded the patient as a regional/remote resident. A greater proportion of first episodes for non-English-speaking patients began when the patient was unstable, deteriorating or terminal, ended in death and were more likely to be associated with high family/carer problems. Community PC setting predicted high symptom burden, with the exception of pain. CONCLUSION: A large proportion of first-time specialist PC episodes in pancreatic cancer begin at a deteriorating phase and end in death, suggesting late access to PC. Timely referrals to community-based specialist PC, access in regional/remote areas, as well as development of culturally diverse support systems require further investigation.

Critical Phenological Events Affect Chemical Defense of Plant Tissues: Iridoid Glycosides in a Woody Shrub.

Plants are chemically-complex organisms; each individual contains diverse tissue-types, has the ability to differentially allocate secondary metabolites to these tissues and can change this allocation through time. The interaction of variation in chemical defense of different tissue types and variation in chemical defense through time, however, is rarely examined and has not been studied for iridoid glycoside-producing woody plants. In this study, we quantified allocation of iridoid glycosides (IGs) to the leaves, flowers, fruits, and seeds of 25 individuals of a long-lived shrub (Lonicera x bella Zabel, Caprifoliaceae), at five important phenological timepoints (leaf-out, flowering, fruit appearance, fruit ripening, and fruit dispersal) throughout a growing season. We found that leaves had 2x higher IG concentrations during flowering and fruiting than earlier in the season (after leaf-out), and later in the season (after fruit dispersal). The individual IG driving this increase in leaves during reproduction, secologanin, was also the most abundant IG in semiripe fruits. Flowers and seeds were composed of different proportions of individual IGs than fruits or leaves, but did not change across time and had overall low concentrations of IGs. In L. x bella, phenological events such as flowering and fruiting lead to an increase in leaf chemical defense that is likely to influence interactions with leaf-feeders. Our results stress the importance of considering phenology when sampling plants for the quantification of chemical defenses.

Palliative care symptoms and problems in a culturally and linguistically diverse population: large retrospective cohort study.

OBJECTIVES: Migrant Australians with cancer have higher unmet needs and poorer health-related quality of life. Less is known about their palliative care experience. We aimed to assess comparative symptom distress and problem severity for culturally and linguistically diverse Australians with cancer in palliative care. METHODS: This was a retrospective, consecutive cohort study using data from the Palliative Care Outcomes Collaboration, which routinely collects standardised symptom assessments nationally at point-of-care. Adults with a cancer diagnosis who died 01/01/2016-31/12/2019 were included. The presence/absence of patient-reported symptom distress and clinician-rated problem severity were compared between people who preferred English and people who preferred another language using logistic regression models. We also compared people who preferred English and the four most common non-English languages in the dataset: Chinese, Greek, Italian and Slavic. RESULTS: A total of 53 964 people with cancer died within the study period, allowing analysis of 104 064 assessments. People preferring non-English languages were less likely to report symptoms (pain: OR=0.89 (0.84 to 0.94); all other symptoms except fatigue OR<1 and CIs did not contain 1). Except for family/carer problems (OR=1.24 (1.12 to 1.31)), linguistically diverse people were less likely to report problems. Variation was seen between non-English language groups. CONCLUSIONS: We did not find evidence of comparatively worse symptom distress or problem severity for nearly all scores for culturally and linguistically diverse Australians. Better symptom management or differential reporting may explain this. It is important to examine this further, including assessing differences within cultural and linguistic groups to ensure the delivery of high-quality palliative care.

Population-level, patient-reported outcomes: a case study regarding a public health intervention that involves patients with life-limiting illnesses.

Introduction: Dying and death are public health concerns, but little is known about public health interventions that target populations living with life-limiting illnesses. This gap makes it difficult to identify best-practice public health interventions for this population and to achieve public health objectives. The study aimed to describe a public health intervention that intends to improve population-level outcomes using point-of-care and patient-reported outcomes. Methods: A case study approach, informed by the Organization for Economic Co-operation and Development's (OECD) Best-Practice Public Health Framework, was used to describe coverage, effectiveness, and equity using mixed methods. Data from 2012 to 2022 were analyzed. Results: Over the 10-year period, the number of deaths recorded in the programme (n = 16,358 to 32,421, +98.2%) as well as the percentage of the population that might benefit from palliative care increased (14.8% to 25.1%). The median age of those admitted for care (74 to 77 years) and the proportion of services participating in the programme located in outer regional and remote areas of Australia increased (2012: 59; 2022: 94; +5.4%). The access by patients that experience the greatest socioeconomic disadvantage decreased (2012: 18.2% n = 4,918; 2022: 15.9% n = 9,525). Improvements in relation to moderate distress related to pain were identified (2012: 63% n = 8,751, 2022: 69% n = 13,700), and one in five instances of severe distress related to pain did not improve (2012: 20% n = 781; 2022: 19% n = 635). Conclusion: Population-level, patient-reported outcome data are useful and necessary in addressing public health objectives in populations with life-limiting illnesses. Our application of the OECD's Best-Practice Public Health Framework has helped to identify and describe a national intervention that may be transferred to other settings to address health promotion objectives. This may help improve the targeting of treatments to improve pain and issues related to equity.

Appetite-Related Distress Is Burdensome in the Last Sixty Days of Life of People Receiving Palliative Care: A National Longitudinal Consecutive Cohort Study.

Background: People with life-limiting illnesses experience a range of distressing symptoms. Appetite-related symptoms are common, but studies have found varied prevalence and the distress caused has had limited quantification. Objectives: To examine the clinicodemographic factors and trajectory of appetite-related distress in the last 60 days of life. Design/Setting/Subjects: Consecutive cohort of 109,385 patients (359,038 data points) using specialist palliative care services in the Australian Palliative Care Outcomes Collaboration (PCOC). Measurements: Patient-reported appetite-related distress using the PCOC Symptom Assessment Scale. Results: Diagnoses included cancer (75%), end-stage organ failure (11%), neurodegenerative disease (4%), dementia (3%), and other noncancer (7%). Fifty-eight percent reported some degree of appetite-related distress at least once in the last 60 days of life. Daily mean distress scores did not vary greatly by diagnosis and the distributions of symptom severity were not linked with performance status. There was a sharp decline in mean distress for all diagnostic groups around 7-10 days before death. Moderate to severe distress was associated with nausea-, bowel-, pain-, and breathing-related distress, controlling for key baseline factors. Conclusion: Appetite-related distress is prevalent and burdensome in the 60 days before death and is strongly associated with distress from other cardinal symptoms.

The Level of Distress From Fatigue Reported in the Final Two Months of Life by a Palliative Care Population: An Australian National Prospective, Consecutive Case Series.

CONTEXT: Fatigue is the most commonly reported symptom in life-limiting illnesses, although not much is known about the distress it causes patients as they approach death. OBJECTIVES: To map the trajectory of distress from fatigue reported by an Australian palliative care population in the last 60 days leading up to death. METHODS: A prospective, longitudinal, consecutive cohort study using national data from the Australian Palliative Care Outcomes Collaboration between July 1, 2013, and December 31, 2018. Patients were included if they had at least one measurement of fatigue on a 0-10 numerical rating scale in the 60 days before death. Descriptive statistics were used to analyse patients by diagnostic cohort and functional status. RESULTS: A total of 116,604 patients from 203 specialist palliative care services were analyzed, providing 501,104 data points. Distress from fatigue affected up to 80% of patients referred to palliative care, with the majority experiencing moderate or severe distress. Malignant and nonmalignant diagnoses were equally affected, with the neurological cohort showing the greatest variability. The degree of distress correlated with a patient's functional level; it worsened as a patient's function declined until a patient became bedbound when the reporting of distress reduced. CONCLUSIONS: Distress from fatigue is high in this cohort of patients. Interventions to reduce this distress need to be a research priority.

Hypertension prevalence in patients attending tertiary pain management services, a registry-based Australian cohort study.

Persistent pain and hypertension often co-occur, and share several biological and lifestyle risk factors. The present study aimed to provide insight into the prevalence of, and factors associated with, hypertension in the largest cohort of patients seeking treatment in 43 tertiary pain clinics in Australia. Adults aged > = 18 years registered to the electronic Persistent Pain Outcomes Collaboration registry between 2013 and 2018 were included if they had persistent non-cancer pain (N = 43,789). Risk Ratios (RRs) compared prevalence of self-reported hypertension with the general and primary care Australian populations, and logistic regression examined factors associated with hypertension. One in four (23.9%) patients had hypertension, which was higher than the Australian adult population (2014-15: RR = 5.86, 95%CI: 5.66, 6.06; 2017-18: RR = 9.40, 95%CI: 9.01, 9.80), and in primary care patients (2011-13: RR = 1.17, 95%CI: 1.15, 1.20). Adjusting for covariates, patients with higher odds of hypertension were older, lived in regions with higher socioeconomic disadvantage, had higher levels of BMI, were born outside the Oceania/Australasia region, and had comorbid arthritis, diabetes, or severe-extremely severe anxiety symptoms. Female patients and those with depression symptoms had lower adjusted odds. Unadjusted analyses showed an association between widespread pain, pain duration, pain severity and interference, and lower pain self-efficacy with hypertension; however, only pain severity remained significant in adjusted analyses. Hypertension was more prevalent in people with persistent pain than in the general community, was associated with more severe pain, and commonly co-occurred with pain-related impairments. Routine hypertension screening and treatment targeting shared mechanisms of hypertension and pain may improve treatment outcomes in the pain clinic setting.

The Paediatric electronic Persistent Pain Outcomes Collaboration (PaedePPOC): establishment of a binational system for benchmarking children's persistent pain services.

Chronic or persistent pain is a growing global health problem. Effective management of pain emerging in childhood may prevent long-term health and vocational consequences. Internationally, paediatric pain services are a limited resource and, as such, must strive to improve equity, outcomes, and value for money. The Paediatric electronic Persistent Pain Outcomes Collaboration (PaedePPOC) is a binational paediatric outcome measurement centre that aims to measure, benchmark, and improve children's specialist pain services in Australasia. This study documents the establishment of PaedePPOC and presents baseline and initial outcome data. Binational consensus meetings determined the measures. Governance structures, collection protocols, information technology, site-specific logistics, and onsite training were achieved within 18 months. Children and parents complete baseline and progress questionnaires. Seven of 10 Australasian services provided data to PaedePPOC, with 1432 patients enrolled until June 2018. At baseline, patients were 12.4 ± (3.0) years, 68% female, 93% Australian-born, and 5% Aboriginal and/or Torres Strait Islander people. Most had moderate-severe functional disability and impaired quality of life, with pain affecting school attendance and employment. Opioid-containing medicines were used often or daily by 16%. Patients completing outcome measures at treatment end reported clinically significant improvement in pain intensity (49% of patients), functional ability (59%), and quality of life (69%). The PaedePPOC initiative has been successfully integrated into children's pain services, yielding timely point-of-care information to support clinicians and families, and valuable binational and service data to inform quality improvement and future sector planning.

Prioritizing a sequence of short-duration groups as the standardized pathway for chronic noncancer pain at an Australian tertiary multidisciplinary pain service: preliminary outcomes.

OBJECTIVE: To describe implementation and report preliminary outcomes of a resource-efficient, standardized group pathway for chronic noncancer pain. DESIGN: Descriptive cross-sectional study of a group-based pain management pathway in comparison with an Australasian benchmarking data set. SETTING: An Australian tertiary multidisciplinary pain service. SUBJECTS: Patients with chronic noncancer pain actively participating in the group pathway in 2016. METHODS: Referred patients were prioritized to a short-duration group-based standardized pain management pathway linking education, assessment, and treatment groups. Measures of pain, mood, self-efficacy, and catastrophizing and reduction in daily opioid use were collated from the Australasian data set. RESULTS: In 2016, 928 patients were actively engaged with the pain service. More patients were prioritized to receive treatment in a group format in comparison with other Australasian services (68.4% vs 22%). A greater percentage of patients attended their first clinical contact within 3 months of referral (81.4%) compared with the Australasian average (68.6%). Comparable improvements in average pain intensity, pain interference, depression, anxiety, stress, pain catastrophizing, and self-efficacy were observed. There was significantly greater reduction in opioid use, including for those taking more than 40 mg of oral morphine equivalent daily dose. CONCLUSION: Implementation of a sequence of short-duration groups as the default clinical pathway resulted in shorter waiting times and noninferior outcomes in key areas for patients completing the program, compared with Australasian averages. Given the resource efficiencies of the group process, this finding has implications for service design.

Normative data for common pain measures in chronic pain clinic populations: closing a gap for clinicians and researchers.

Normative data for chronic pain questionnaires are essential to the interpretation of aggregate scores on these questionnaires, for both clinical trials and clinical practice. In this study, we summarised data from 13,343 heterogeneous patients on several commonly used pain questionnaires that were routinely collected from 36 pain clinics in Australia and New Zealand as part of the electronic Persistent Pain Outcomes Collaboration (ePPOC) including the Brief Pain Inventory (BPI); the Depression Anxiety and Stress Scales (DASS); the Pain Self-Efficacy Questionnaire (PSEQ); and the Pain Catastrophizing Scale (PCS). The data are presented as summarised normative data, broken down by demographic (age, sex, work status, etc) and pain site/medical variables. The mean BPI severity score was 6.4 (moderate-severe), and mean interference score was 7.0. The mean DASS depression score was 20.2 (moderate-severe), mean DASS anxiety was 14.0 (moderate), and mean DASS stress was 21.0 (moderate). The mean PCS scores were 10.0, 5.9, 14.1, and 29.8 for rumination, magnification, helplessness, and total, respectively. The mean PSEQ score was 20.7. Men had slightly worse scores than women on some scales. Scores tended to worsen with age until 31 to 50 years, after which they improved. Scores were worse for those who had a greater number of pain sites, were unemployed, were injury compensation cases, or whose triggering event was a motor vehicle accident or injury at work or home. These results and comparisons with data on the same measures from other countries, as well as their uses in both clinical practice and clinical trials, are discussed.

Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: a phase one open-label study.

BACKGROUND: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH)2 vitamin D3 of CD4+ cells from CF patients with ABPA decreases Aspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D3 supplementation in CF patients with ABPA to reduce allergic responses and ABPA symptoms, and increase serum vitamin D levels. METHODS: Seven patients ages 12 years and older with a clinical diagnosis of CF and ABPA with current evidence of Af sensitization received 4000 IU vitamin D3 (cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by the Aspergillus induced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reduces Aspergillus induced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE, Aspergillus-specific IgE, vitamin D levels, FEV1, urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells. RESULTS: Six months of vitamin D3 supplementation resulted in significant increases in serum 25-(OH) vitamin D level, and the treatment was well tolerated without evidence of vitamin D toxicity or hypercalcemia. There were no serious adverse events. Daily vitamin D supplementation led to significantly decreased Aspergillus induced IL-13 responses between the baseline visit and that at 24 weeks (p = 0.04). Aspergillus-specific IgE level was also significantly decreased after 8 (p = 0.035) and 24 weeks of daily vitamin D supplementation (p = 0.04). CONCLUSIONS: 4000 IU vitamin D3 daily over a 24-week period is well tolerated in CF patients with a history ABPA and current evidence of Th2 immunity to Af. . Daily vitamin D supplementation was associated with reduced Aspergillus induced IL-13 responses from peripheral. . CD4+ T cells and Aspergillus-specific IgE levels, as well as increased serum vitamin D levels. This treatment was well tolerated and the study supports further investigation of the use of vitamin D supplementation in Th2 mediated diseases. TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov as NCT01222273.

Does polyembryony confer a competitive advantage to the invasive perennial vine Vincetoxicum rossicum (Apocynaceae)?

Determining which traits may allow some introduced plant species to become invasive in their new environment continues to be a key question in invasion biology. Vincetoxicum rossicum is an invasive, perennial vine colonizing natural and seminatural habitats primarily in the northeastern United States and southeastern Canada. More than half its seeds exhibit polyembryony, a relatively uncommon condition in which a single seed produces multiple seedlings. For evaluating the potential consequences of polyembryony on invasiveness, V. rossicum plants derived from seeds of three embryonic classes-singlets, doublets, and triplets (one, two, and three seedlings per seed, respectively)-were paired in all combinations intraspecifically and with the co-occurring native herbs Solidago canadensis and Asclepias syriaca in a greenhouse study. Vincetoxicum rossicum biomass was 25-55% greater and follicle production 55-100% greater under intraspecific competition compared with interspecific competition. However, within a competitive environment, follicle production varied little. Regardless of competitive environment, V. rossicum originating from seeds with a greater number of embryos typically performed no better than plants arising from seed with fewer embryos (singlets = doublets = triplets)-except intraspecifically where doublets outperformed singlets, and with S. canadensis where triplets outperformed singlets. Our findings suggest that overall performance and fitness of V. rossicum is higher in monocultures than in mixed stands and that its ability to invade new habitats may not be attributable to the production of polyembryonic seeds.

Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%-15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA. Therefore, we compared cohorts of A. fumigatus-colonized CF patients with and without ABPA to identify factors mediating tolerance versus sensitization. We found that the costimulatory molecule OX40 ligand (OX40L) was critical in driving Th2 responses to A. fumigatus in peripheral CD4+ T cells isolated from patients with ABPA. In contrast, CD4+ T cells from the non-ABPA cohort did not mount enhanced Th2 responses in vitro and contained a higher frequency of TGF-beta-expressing regulatory T cells. Heightened Th2 reactivity in the ABPA cohort correlated with lower mean serum vitamin D levels. Further, in vitro addition of 1,25 OH-vitamin D3 substantially reduced DC expression of OX40L and increased DC expression of TGF-beta. This in vitro treatment also resulted in increased Treg TGF-beta expression and reduced Th2 responses by CD4+ T cells from patients with ABPA. These data provide rationale for a therapeutic trial of vitamin D to prevent or treat ABPA in patients with CF.