An evidence-base for the implementation of hospital-based palliative care programs in routine cancer practice:A systematic review

Background: Despite global support, there remain gaps in the integration of early palliative care into cancer care. The methods of implementation whereby evidence of benefits of palliative care is translated into practice deserve attention. Aim: To identify implementation frameworks utilised in integrated palliative care in hospital-based oncology services and to describe the associated enablers and barriers to service integration. Design: Systematic review with a narrative synthesis including qualitative, mixed methods, pre-post and quasi experimental designs following the guidance by the Centre for Reviews and Dissemination (PROSPERO registration CRD42021252092). Data sources: Six databases searched in 2021: EMBASE, EMCARE, APA PsycINFO, CINAHL, Cochrane Library and Ovid MEDLINE searched in 2023. Included were qualitative or quantitative studies, in English language, involving adults >18 years, and implementing hospital-based palliative care into cancer care. Critical appraisal tools were used to assess the quality and rigour. Results: Seven of the 16 studies explicitly cited the use of frameworks including those based on RE-AIM, Medical Research Council evaluation of complex interventions and WHO constructs of health service evaluation. Enablers included an existing supportive culture, clear introduction to the programme across services, adequate funding, human resources and identification of advocates. Barriers included a lack of communication with the patients, caregivers, physicians and palliative care team about programme goals, stigma around the term ‘palliative’, a lack of robust training, or awareness of guidelines and undefined staff roles. Conclusions: Implementation science frameworks provide a method to underpin programme development and evaluation as palliative care is integrated within the oncology setting.Farwa Rizvi, Helen Elizabeth Wilding, Nicole M Rankin, Roslyn Le Gautier, Lorna Gurren, Vijaya Sundararajan, Kylee Bellingham, Joyce Chua, Gregory B Crawford, Anna K Nowak, Brian Le, Geoff Mitchell, Sue-Anne McLachlan, Tanara Vieira Sousa, Robyn Hudson, Maarten IJzerman, Anna Collins, and Jennifer Phili

What’s missing from legal geography and materialist studies of law? Absence and the assembling of asylum appeal hearings in Europe

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: Due to the ethical and legally sensitive nature of the research, ethnographic notes taken in court could not be made openly available. Appellant interviewees were not asked for their permission to share their interview transcripts in an online open archive because of concerns that they could misunderstand what was being asked for, or feel obliged to agree but subsequently feel less able to conduct free conversation in research interviews as a result, thereby negatively impacting on the quality of the data generated. Additional details relating to, and data resulting from, to a survey taken during observations of British asylum appeals between 2013 and 2016 are available from the UK Data Archive (persistent identifier: 10.5255/UKDA-SN-852032).There is an absence of absence in legal geography and materialist studies of the law. Drawing on a multi‐sited ethnography of European asylum appeal hearings, this paper illustrates the importance of absences for a fully‐fledged materiality of legal events. We show how absent materials impact hearings, that non‐attending participants profoundly influence them, and that even when participants are physically present, they are often simultaneously absent in other, psychological registers. In so doing we demonstrate the importance and productivity of thinking not only about law's omnipresence but also the absences that shape the way law is experienced and practiced. We show that attending to the distribution of absence and presence at legal hearings is a way to critically engage with legal performance.Economic and Social Research Council (ESRC)European Research Council (ERC

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Upscaling marine forest restoration: challenges, solutions and recommendations from the Green Gravel Action Group

IntroductionTo counteract the rapid loss of marine forests globally and meet international commitments of the UN Decade on Ecosystem Restoration and the Convention on Biological Diversity ‘30 by 30’ targets, there is an urgent need to enhance our capacity for macroalgal restoration. The Green Gravel Action Group (GGAG) is a global network of 67 members that are working on the restoration of a diverse range of macroalgal forests and it aims to facilitate knowledge exchange to fast-track innovation and implementation of outplanting approaches worldwide. MethodsHere, we overview 25 projects conducted by members of the group that are focused on testing and developing techniques for macroalgal restoration. Based on these projects, we summarise the major challenges associated with scaling up the area of marine forests restored. ResultsWe identify several critical challenges that currently impede more widespread rollout of effective large-scale macroalgal restoration worldwide: 1) funding and capacity limitations, 2) difficulties arising from conditions at restoration sites, 3) technical barriers, and 4) challenges at the restoration-policy interface. DiscussionDespite these challenges, there has been substantial progress, with an increasing number of efforts, community engagement and momentum towards scaling up activities in recent years. Drawing on the collective expertise of the GGAG, we outline key recommendations for the scaling up of restoration efforts to match the goals of international commitments. These include the establishment of novel pathways to fund macroalgal restoration activities, building skills and capacity, harnessing emerging innovations in mobile hatchery and seeding technologies, and the development of the scientific and governance frameworks necessary to implement and monitor macroalgal restoration projects at scale

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Controlled retrieval processing in recognition memory exclusion tasks

ERPs were acquired in the test phases of two memory tasks where three classes of word were presented: (i) words encountered in a study phase (studied words), (ii) words presented at test for the first time (new words), and (iii) new words repeated after a lag of 7–9 words (repeated test words). In Experiment 1, participants responded on one key to studied words (targets) and on a second to repeated test words (non-targets) as well as to new words. In Experiment 2, participants responded on one key to repeated test words (targets) and on a second key to new and studied words (non-targets). The likelihood of a correct response to a target was higher in Experiment 2 than in Experiment 1. In both experiments, the focus for the ERP analyses was on parietally distributed ERP old/new effects, which are assumed to index recollection. Reliable parietal old/new effects were obtained for targets as well as non-targets in Experiment 1, but for targets only in Experiment 2. This pattern of data is consistent with previous suggestions that, when the likelihood of recollecting information about targets is high, participants use the success or failure of an attempt to recollect information about targets as the basis for distinguishing between targets and all other classes of test word. The findings in these two experiments are informative because they: (i) generalise those obtained in previous work to a different exclusion paradigm, (ii) add emphasis to claims regarding the potential utility of this particular paradigm in studies where changes in memory control according to age are assessed, and (iii) highlight important considerations when behavioural data obtained in exclusion tasks are employed in order to make estimates of the relative contributions of recollection and familiarity to task performance

Electrophysiological correlates of familiarity in recognition memory and exclusion tasks

ERPs were acquired in the test phases of three memory experiments, where three classes of word were presented. These were: (i) words encountered in a prior study phase (studied words), (ii) words presented at test for the first time (new words), and (iii) new words repeated after a lag of 7–9 intervening words (repeated test words). In experiments 1 and 2, participants were asked to respond on one key to studied words and on another to new as well as to repeated test words. In experiment 3, a binary response was again required, but in this case repeated test and studied words were assigned to the same key. In each experiment, the principal focus for analysis was on the differences between the ERPs at mid-frontal electrode locations from 300 to 500 ms post-stimulus that were associated with incorrect responses to studied words (misses) and correct responses to new words. It has been proposed that relatively greater positivity for studied than for new words at this locus reflects the greater familiarity of studied than of unstudied words. ERPs elicited by misses were reliably more positive-going than those elicited by correct rejections in experiments 1 and 2 only. These findings support the link between this modulation of the electrical record and familiarity in so far as the designs of the experiments lead to the prediction that the average level of familiarity associated with misses should be higher in the first two experiments than in the third. In combination with findings in other studies, these data support dual-process accounts of recognition memory

Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: a new paradigm for cardiovascular compromise in the preterm newborn

Objective: H 2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H 2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition. Methods: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H 2 S, was determined by high-performance liquid chromatography. Real-time H 2 S production was assessed using a microrespiration system in fetal and postnatal (10, 24 hours) skin and heart samples. CSE contribution was investigated by inhibition via propargylglycine. Results: In preterm animals, postnatal H 2 S production capacity in peripheral vasculature increased significantly and was significantly reduced by the inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood flow and capacity of the vasculature to produce H 2 S. H 2 S produced via CSE did not correlate directly with microvascular blood flow. Conclusions: In preterm neonates, H 2 S production increases during fetal-to-neonatal transition and CSE contribution to total H 2 S increases postnatally. CSE-dependent mechanisms may therefore underpin the increase in H 2 S production over the first 72 hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability