Search

Background: The need for home-based palliative care is accelerating internationally. At the same time, health systems face increased complexity, funding constraints and global shortages in the healthcare workforce. As such, ambulance services are increasingly tasked with providing palliative care. Where paramedics with additional training in palliative care have been integrated into models of care, evaluations have been largely positive. Studies of patient and family carer experiences of paramedic involvement, however, are limited. Aim: To explore patient and family caregiver experiences of paramedics’ contribution to palliative care at home. Design: Qualitative interview study. We analysed data within a social constructionist epistemology using reflexive thematic analysis. Setting/participants: Participants receiving specialist palliative care in the community of a metropolitan city of Australia who requested an ambulance between January and August 2018, inclusive. Results: Participants considered paramedics with expertise and experience in palliative care as an extension of the specialist community palliative care team and held them in high regard. Participants highlighted the importance of: critical palliative care at home and a timely, responsive approach; person-centred paramedics; as well as safety and security. Conclusion: Patients and carers feel safe and secure when they know that highly responsive skilled professional support is available when an unexpected problem or sudden change arises, especially out-of-hours, and that support is delivered in an empathic and person-centred manner.

Background Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Oesophago-Gastric (OG) malignancies in patients who have had a prior bariatric procedure have not been fully characterised. Objective To characterise OG malignancies after bariatric procedures. Setting University Hospital, United Kingdom. Methods We performed a retrospective, multi-centre observational study of patients with OG malignancies after bariatric surgery to characterise this condition. Results This study includes 170 patients from 75 centres in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years and the mean weight 128.8 ± 28.9 kg. Females comprised 57.3% (n=98) of the population. Most (n=64) patients underwent a Roux-en-Y Gastric Bypass (RYGB) followed by Adjustable Gastric Band (AGB) (n = 46) and Sleeve Gastrectomy (SG) (n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One-third of patients presented with metastatic disease. The majority of tumours were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under one year for most patients who died over the intervening period. Conclusions The OGMOS (Oesophago-Gastric Malignancies after Obesity/ Bariatric Surgery) study presents the largest series to date of patients developing OG malignancies after bariatric surgery and attempts to characterise this condition.

This article examines the 2020 decisions of the High Court on constitutional law through the lens of the Communist Party Case, taking the 70th anniversary of that decision as an opportunity to reflect on the ongoing utility and efficacy of the constitutional principles it espoused. It focuses on the way in which constitutional meaning may be informed by ordinary legislation, the common law and the rich backdrop of principles and values against which the Constitution was drafted — particularly, the rule of law. In doing so, the article highlights enduring questions about the scope of the High Court’s power to remedy those deficiencies in the Constitution that reveal themselves over time.

Therapeutic angiogenesis aims to induce new blood vessel growth in ischemic tissues; however, previous clinical trials have had limited success. Studies of uterine angiogenesis revealed a specialized subset of natural killer (NK) cells, called uterine NK (uNK) cells, which have unique proangiogenic abilities.We show that uNK cells in mice express ephrin-B2, a regulator of angiogenesis, to induce tubule formation in an ex vivo coculture tubule formation assay. We next induced the expression of ephrin-B2 by splenic NK (sNK) cells harvested from male mice.We showed that induced NK (iNK) cells can also instruct endothelial cells to form tubules using ephrin-B2.We concluded that Ephrin-B2 is a marker of proangiogenic uNK cells and that a proangiogenic phenotype characterized by ephrin-B2 can be induced in sNK cells to induce therapeutic angiogenesis.

Pluripotent human embryonic stem cell (hESC) lines are a valuable in vitro tool to differentiate specific cell lineages, including cells from all three germ layers, i.e., neuronal cells, myocytes, and hematopoietic cells, including progenitors (described here), lymphoid cells, and myeloid cells. However, dramatically different cell subtypes and functional properties of specific cells can arise depending on the differentiation technique used. We previously optimized hematopoietic stem cell differentiation from two different NIH-approved hESC lines to generate CD34

The POLISH2 optical polarimeter has been in operation at the Lick Observatory 3-m Shane telescope since 2011, and it was commissioned at the Gemini North 8-m in 2016. This instrument primarily targets exoplanets, asteroids, and the Crab pulsar, but it has also been used for a wide variety of planetary, galactic, and supernova science. POLISH2's photoelastic modulators, employed instead of rotating waveplates or ferro-electric liquid crystal modulators, offer the unprecedented ability to achieve sensitivity and accuracy of order 1 ppm (0.0001%), which are difficult to obtain with conventional polarimeters. Additionally, POLISH2 simultaneously measures intensity (Stokes I), linear polarization (Stokes Q and U), and circular polarization (Stokes V), which fully describe the polarization state of incident light. We document our laboratory and on-sky calibration methodology, our archival on-sky database, and we demonstrate conclusive detection of circular polarization of certain objects., 38 pages, 16 figures, accepted by ApJS

Telehealth use has increased in the setting of the COVID-19 pandemic. However, there are disparities in telehealth use based on age, income, race/ethnicity, low health, digital literacy, and limited English proficiency. There are multilevel barriers to telehealth use at the patient, health systems, telehealth portal, and policy levels. To ensure equity in telehealth services and to leverage these services to maximize the reach of health care services, concerted efforts are needed to design telehealth tools and workflows. It should include reimbursement for staff training, patient education, and technical support needed for telehealth use. Furthermore, ongoing monitoring and responsive modifications in the use of telehealth services are needed to promote telehealth equity.

Background Home death is one of the key performance indicators of the quality of palliative care service delivery. Such a measure has direct implications on everyone involved at the end of life of a dying patient, including a patient’s carers and healthcare professionals. There are no studies that focus on the views of the team of integrated inpatient and community palliative care service staff on the issue of preference of place of death of their patients. This study addresses that gap. Methods Thirty-eight participants from five disciplines in two South Australian (SA) public hospitals working within a multidisciplinary inpatient and community integrated specialist palliative care service, participated in audio-recorded focus groups and one-on-one interviews. Data were transcribed and thematically analysed. Results Two major and five minor themes were identified. The first theme focused on the role of healthcare professionals in decisions regarding place of death, and consisted of two minor themes, that healthcare professionals act to: a) mediate conversations between patient and carer; and b) adjust expectations and facilitate informed choice. The second theme, healthcare professionals’ perspectives on the preference of place of death, comprised three minor themes, identifying: a) the characteristics of the preferred place of death; b) home as a romanticised place of death; and c) the implications of idealising home death. Conclusion Healthcare professionals support and actively influence the decision-making of patients and family regarding preference of place of death whilst acting to protect the relationship between the patient and their family/carer. Further, according to healthcare professionals, home is neither always the most preferred nor the ideal place for death. Therefore, branding home death as the ideal and hospital death as a failure sets up families/carers to feel guilty if a home death is not achieved and undermines the need for and appropriateness of death in institutionalised settings.

Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer.A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance.Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis.Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.

Policy-mandated requirements for use of evidence-based programs (EBP) in place-based initiatives are becoming more common. Little attention has been paid to the geographic aspects of uneven market development and urbanicity in implementing EBPs in large place-based initiatives. The aim of this study was to explore geographic variation in knowledge, attitudes, and experiences of service providers who implemented an EBP policy in Australia's largest place-based initiative for children, Communities for Children. A cross-sectional online survey of Communities for Children service providers was conducted in 2018-2019, yielding 197 participants from all of Australia's eight states and territories. Relationships between two measures of 'place' (thick and thin market states; urbanicity: urban, regional and remote) and study-designed measures of knowledge, attitudes, and implementation experiences were analyzed using adjusted logistic and multinomial regressions. Participants from thin market states (outside the Eastern Seaboard) were more resistant to the policy and experienced greater implementation challenges than those from thick market states (Eastern Seaboard). Regional participants reported greater knowledge about EBPs but experienced greater dissatisfaction and implementation challenges with the policy than both urban and remote participants. Our study found that place does matter when implementing EBPs in a place-based initiative.

Regulation has long since guided urban growth, and it is essential for municipalities to construct regulation that is conducive to creating visually stimulating public spaces. Minimal scientific research has been conducted on the impacts of commercial signage and the varying arrangements created by different sign regulations in regard to perception (Jourdan, Hurd, & Hawkins, 2013; Portella, 2014). With the rise of public involvement in planning (Lane, 2005; Sanoff, 2000), it is essential that designers and non-designers coordinate to develop sign controls that contribute to urban growth. This research studies the differences and similarities in perceptions of planning and design professionals and non-designers to aid in the development of future, more positively perceived, signage regulation. By using visual models presented in the form of a survey, findings show both similarities and differences between these groups in their assessment of signscapes regarding communication, perceptions of characteristics like beauty, interest, and order, an overall preference toward highly structured codes, and a difference in harshness of evaluation.

Background Current international consensus is that ‘early’ referral to palliative care services improves cancer patient and family carer outcomes. In practice, however, these referrals are not routine. An approach which directly addresses identified barriers to early integration of palliative care is required. This protocol details a trial of a standardized model of early palliative care (Care Plus) introduced at key defined, disease-specific times or transition points in the illness for people with cancer. Introduced as a ‘whole of system’ practice change for identified advanced cancers, the key outcomes of interest are population health service use change. The aims of the study are to examine the effect of Care Plus implementation on (1) acute hospitalisation days in the last 3 months of life; (2) timeliness of access to palliative care; (3) quality and (4) costs of end of life care; and (5) the acceptability of services for people with advanced cancer. Methods Multi-site stepped wedge implementation trial testing usual care (control) versus Care Plus (practice change). The design stipulates ‘control’ periods when usual care is observed, and the process of implementing Care Plus which includes phases of planning, engagement, practice change and evaluation. During the practice change phase, all patients with targeted advanced cancers reaching the transition point will, by default, receive Care Plus. Health service utilization and unit costs before and after implementation will be collated from hospital records, and state and national health service administrative datasets. Qualitative data from patients, consumers and clinicians before and after practice change will be gathered through interviews and focus groups. Discussion The study outcomes will detail the impact and acceptability of the standardized integration of palliative care as a practice change, including recommendations for ongoing sustainability and broader implementation. Trial registration Australian New Zealand Clinical Trials Registry ACTRN 12619001703190. Registered 04 December 2019.

Cannabis is well established as possessing immune modulating activity. The objective of this study was to evaluate the anti-inflammatory properties of selected cannabis-derived terpenes and cannabinoids. Based on their activity in cannabis-chemovar studies, α-pinene, trans-nerolidol, D-limonene, linalool and phytol were the selected terpenes evaluated. The cannabinoid compounds evaluated included cannabidivarin, cannabidiol, cannabinol, cannabichromene, cannabigerol and delta-9-tetrahydrocannabinol. Human PBMC were pretreated with each compound, individually, at concentrations extending from 0.001 to 10 μM and then stimulated with CpG (plasmacytoid dendritic cell), LPS (monocytes), or anti-CD3/CD28 (T cells). Proliferation, activation marker expression, cytokine production and phagocytosis, were quantified. Of the 21 responses assayed for each compound, cannabinoids showed the greatest immune modulating activity compared to their vehicle control. Delta-9-tetrahydrocannabinol possessed the greatest activity affecting 11 immune parameters followed by cannabidivarin, cannabigerol, cannabichromene, cannabinol and cannabidiol. α-Pinene showed the greatest immune modulating activity from the selected group of terpenes, followed by linalool, phytol, trans-nerolidol. Limonene had no effect on any of the parameters tested. Overall, these studies suggest that selected cannabis-derived terpenes displayed minimal immunological activity, while cannabinoids exhibited a broader range of activity. Compounds possessing anti-inflammatory effects may be useful in decreasing inflammation associated with a range of disorders, including neurodegenerative disorders.

Urinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits.This study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected.A total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%).Our findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Translocator protein 18 kDa (TSPO) is a well-known outer mitochondrial membrane protein and it is widely used as a biomarker of neuroinflammation and brain injury. Although it is thought that TSPO plays key roles in a multitude of host cell functions, including steroid biosynthesis, apoptosis, generation of reactive oxygen species, and proliferation, some of these functions have recently been questioned. Here, we report the unexpected finding that circulating immune cells differentially express basal levels of TSPO on their cell surface, with a high percentage of monocytes and neutrophils expressing cell surface TSPO. In vitro stimulation of monocytes with LPS significantly increases the frequency of cells with surface TSPO expression in the absence of altered gene expression. Importantly, the LPS increase in TSPO cell surface expression in monocytes appears to be selective for LPS because two other distinct monocyte activators failed to increase the frequency of cells with surface TSPO. Finally, when we quantified immune cell TSPO surface expression in antiretroviral therapy-treated HIV+ donors, a chronic inflammatory disease, we found significant increases in the frequency of TSPO surface localization, which could be pharmacologically suppressed with ∆9-tetrahydrocannabinol. These findings suggest that cell surface TSPO in circulating leukocytes could serve as a peripheral blood-based biomarker of inflammation.

Innate-like B cells (ILBs) are a heterogeneous population B cells which participate in innate and adaptive immune responses. This diverse subset of B cells is characterized by the expression of CD5 and has been shown to secrete high levels of immunoglobulin M (IgM) in the absence of infection or vaccination. Further, CD5+ILBs have been shown to express high basal levels of lymphocyte specific protein tyrosine kinase (LCK) and programmed cell death protein-1 (PD-1), which are particularly sensitive to stimulation by interferon gamma (IFNγ). Previous studies have demonstrated that activation of the aryl hydrocarbon receptor (AHR), a cytosolic ligand-activated transcription factor, results in suppressed IgM responses and is dependent on LCK. A recent study showed that CD5+ILBs are particularly sensitive to AHR activation as evidenced by a significant suppression of the IgM response compared to CD5-B cells, which were refractory. Therefore, the objective of this study was to further investigate the role of LCK and PD-1 signaling in AHR-mediated suppression of CD5+ILBs. In addition, studies were conducted to establish whether IFNγ alters the levels of LCK and PD-1 in CD5+ILBs. We found that AHR activation led to a significant upregulation of total LCK and PD-1 proteins in CD5+ILBs, which correlated with suppression of IgM. Interestingly, treatment with recombinant IFNγ reduced LCK protein levels and reversed AHR-mediated IgM suppression in CD5+ILBs in a similar manner as LCK inhibitors. Collectively, these results support a critical role for LCK and PD-1 in AHR-mediated suppression of the IgM response in human CD5+ILBs.