Setting an International Research Agenda for Fear of Cancer Recurrence: an online delphi consensus study

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionBackground: Fear of cancer recurrence (FCR) is common amongst cancer survivors. There is rapidly growing research interest in FCR but a need to prioritise research to address the most pressing clinical issues and reduce duplication and fragmentation of effort. This study aimed to establish international consensus among clinical and academic FCR experts regarding priorities for FCR research. Methods: Members of the International Psycho-oncology Society (IPOS) Fear of Cancer Recurrence Special Interest Group (FORwards) were invited to participate in an online Delphi study. Research domains identified in Round 1 were presented and discussed at a focus group (Round 2) to consolidate the domains and items prior to presentation in further survey rounds (Round 3) aimed at gaining consensus on research priorities of international significance. Results: Thirty four research items were identified in Round 1 and 33 of the items were consolidated into 6 overarching themes through a focus group discussion with FCR experts. The 33 research items were presented in subsequent rounds of the delphi technique. Twenty one participants contributed to delphi round 1, 16 in round 2 and 25 and 29 participants for subsequent delphi rounds. Consensus was reached for 27 items in round 3.1. A further 4 research items were identified by panellists and included in round 3.2. After round 3.2, 35 individual research items were ratified by the panellists. Given the high levels of consensus and stability between rounds no further rounds were conducted. Overall intervention research was considered the most important focus for FCR research. Panellists identified models of care that facilitate greater access to FCR treatment and evaluation of the effectiveness of FCR interventions in real world settings as the two research items of highest priority. Defining the mechanisms of action and active components across FCR/P interventions, was the third highest priority identified. Conclusions: The findings of this study outline a research agenda for international FCR research. Intervention research to identify models of care that increase access to treatment, are based on a flexible approach based on symptom severity and can be delivered within routine clinical care, were identified as research areas to prioritise. Greater understanding of the active components and mechanisms of action of existing FCR interventions will facilitate increased tailoring of interventions to meet patient need

Tropical understory herbaceous community responds more strongly to hurricane disturbance than to experimental warming

Ecology and Evolution published by John Wiley & Sons Ltd. The effects of climate change on tropical forests may have global consequences due to the forests’ high biodiversity and major role in the global carbon cycle. In this study, we document the effects of experimental warming on the abundance and composition of a tropical forest floor herbaceous plant community in the Luquillo Experimental Forest, Puerto Rico. This study was conducted within Tropical Responses to Altered Climate Experiment (TRACE) plots, which use infrared heaters under free-air, open-field conditions, to warm understory vegetation and soils + 4°C above nearby control plots. Hurricanes Irma and María damaged the heating infrastructure in the second year of warming, therefore, the study included one pretreatment year, one year of warming, and one year of hurricane response with no warming. We measured percent leaf cover of individual herbaceous species, fern population dynamics, and species richness and diversity within three warmed and three control plots. Results showed that one year of experimental warming did not significantly affect the cover of individual herbaceous species, fern population dynamics, species richness, or species diversity. In contrast, herbaceous cover increased from 20% to 70%, bare ground decreased from 70% to 6%, and species composition shifted pre to posthurricane. The negligible effects of warming may have been due to the short duration of the warming treatment or an understory that is somewhat resistant to higher temperatures. Our results suggest that climate extremes that are predicted to increase with climate change, such as hurricanes and droughts, may cause more abrupt changes in tropical forest understories than longer-term sustained warming

Solar radiation and soil moisture drive tropical forest understory responses to experimental and natural hurricanes

Tropical forest understory regeneration occurs rapidly after disturbance with compositional trajectories that depend on species availability and environmental conditions. To predict future tropical forest regeneration dynamics, we need a deeper understanding of how pulse disturbance events, like hurricanes, interact with environmental variability to affect understory demography and composition. We examined fern and sapling mortality, recruitment, and community composition in relation to solar radiation and soil moisture using 17 years of forest dynamics data (2003–2019) from the Canopy Trimming Experiment in the Luquillo Experimental Forest, Puerto Rico. Solar radiation increased 150% and soil moisture increased 40% following canopy trimming of experimental plots relative to control plots. All plots were disturbed in 2017 by Hurricanes Irma and Maria, so experimentally trimmed plots presented the opportunity to study the effects of multiple hurricanes, while control plots isolated the effects of a single natural hurricane. Recruitment rates maximized at 0.14 individuals/plot/month for ferns and 0.20 stems/plot/month for saplings. Recruitment and mortality were distributed more evenly over the 17 years of monitoring in experimentally trimmed plots than in control plots; however, following Hurricane Maria demographic rates substantially increased in control plots only. In experimentally trimmed plots, the largest community compositional shifts occurred as a result of the trimming events, and compositional changes were greatest for control plots after Hurricane Maria in 2017. Pioneer tree and fern species increased in abundance in response to both simulated and natural hurricanes. Following Hurricane Maria, two dominant pioneer species, Cyathea arborea and Cecropia schreberiana, recruited abundantly, but only in control plots. In trimmed plots, increased solar radiation and soil moisture shifted understory species composition steadily toward pioneer and secondary-successional species, with soil moisture interacting strongly with canopy trimming. Thus, both solar radiation and soil moisture are environmental drivers affecting pioneer species recruitment following disturbance, which interact with canopy opening following hurricanes. Our results suggest that if hurricane disturbances increase in frequency and severity, as suggested by climate change predictions, the understory regeneration of late-successional species, such as Manilkara bidentata and Sloanea berteroana, which prefer deeper shade and slightly drier soil microsites, may become imperiled

The difficult doctor? Characteristics of physicians who report frustration with patients: an analysis of survey data

BACKGROUND: Literature on difficult doctor-patient relationships has focused on the "difficult patient." Our objective was to determine physician and practice characteristics associated with greater physician-reported frustration with patients. METHODS: We conducted a secondary analysis of the Physicians Worklife Survey, which surveyed a random national sample of physicians. Participants were 1391 family medicine, general internal medicine, and medicine subspecialty physicians. The survey assessed physician and practice characteristics, including stress, depression and anxiety symptoms, practice setting, work hours, case-mix, and control over administrative and clinical practice. Physicians estimated the percentage of their patients who were "generally frustrating to deal with." We categorized physicians by quartile of reported frustrating patients and compared characteristics of physicians in the top quartile to those in the other three quartiles. We used logistic regression to model physician characteristics associated with greater frustration. RESULTS: In unadjusted analyses, physicians who reported high frustration with patients were younger (p < 0.001); worked more hours per week (p = 0.041); and had more symptoms of depression, stress, and anxiety (p < 0.004 for all). In the final model, factors independently associated with high frustration included age < 40 years, work hours > 55 per week, higher stress, practice in a medicine subspeciality, and greater number of patients with psychosocial problems or substance abuse. CONCLUSION: Personal and practice characteristics of physicians who report high frustration with patients differ from those of other physicians. Understanding factors contributing to physician frustration with patients may allow us to improve the quality of patient-physician relationships

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca