Strategies to address the shortcomings of commonly used advanced chronic heart failure descriptors to improve recruitment in palliative care research: A parallel mixed-methods feasibility study

Background:Recruitment challenges contribute to the paucity of palliative care research with advanced chronic heart failure patients.Aim:To describe the challenges and outline strategies of recruiting advanced chronic heart failure patients.Design:A feasibility study using a pre–post uncontrolled design.Setting:Advanced chronic heart failure patients were recruited at two nurse-led chronic heart failure disease management clinics in IrelandResults:Of 372 patients screened, 81 were approached, 38 were recruited (46.9% conversion to consent) and 25 completed the intervention. To identify the desired population, a modified version of the European Society of Cardiology definition was used together with modified New York Heart Association inclusion criteria to address inter-study site New York Heart Association classification subjectivity. These modifications substantially increased median monthly numbers of eligible patients approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9). Analysis using a mortality risk calculator demonstrated that recruited patients had a median 1-year mortality risk of 22.7 and confirmed that the modified eligibility criteria successfully identified the population of interest. A statistically significant difference in New York Heart Association classification was found in recruited patients between study sites, but no statistically significant difference was found in selected clinical parameters between these patients.Conclusion:Clinically relevant modifications to the European Society of Cardiology definition and strategies to address New York Heart Association subjectivity may help to improve advanced chronic heart failure patient recruitment in clinical settings, thereby helping to address the paucity of palliative care research this population

Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris

Objective: There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls. Methods: Two SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor). Results: Both SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1×10−5 OR 1.33, rs20541 ptrend = 8.0×10−4 OR 1.27), but neither SNP was significantly associated with susceptibility to PsV. Conclusions: This study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA

Social and clinical determinants of preferences and their achievement at the end of life: Prospective cohort study of older adults receiving palliative care in three countries

© 2017 The Author(s). Background: Achieving choice is proposed as a quality marker. But little is known about what influences preferences especially among older adults. We aimed to determine and compare, across three countries, factors associated with preferences for place of death and treatment, and actual site of death. Methods: We recruited adults aged ≥65-years from hospital-based multiprofessional palliative care services in London, Dublin, New York, and followed them for >17 months. All services offered consultation on hospital wards, support for existing clinical teams, outpatient services and received funding from their National Health Service and/or relevant Insurance reimbursements. The New York service additionally had 10 inpatient beds. All worked with and referred patients to local hospices. Face-to-face interviews recorded most and least preferred place of death, treatment goal priorities, demographic and clinical information using validated questionnaires. Multivariable and multilevel analyses assessed associated factors. Results: One hundred and thirty eight older adults (64 London, 59 Dublin, 15 New York) were recruited, 110 died during follow-up. Home was the most preferred place of death (77/138, 56%) followed by inpatient palliative care/hospice units (22%). Hospital was least preferred (35/138, 25%), followed by nursing home (20%) and home (16%); hospice/palliative care unit was rarely least preferred (4%). Most respondents prioritised improving quality of life, either alone (54%), or equal with life extension (39%); few (3%) chose only life extension. There were no significant differences between countries. Main associates with home preference were: cancer diagnosis (OR 3.72, 95% CI 1.40-9.90) and living with someone (OR 2.19, 1.33-3.62). Adults with non-cancer diagnoses were more likely to prefer palliative care units (OR 2.39, 1.14-5.03). Conversely, functional independence (OR 1.05, 1.04-1.06) and valuing quality of life (OR 3.11, 2.89-3.36) were associated with dying at home. There was a mismatch between preferences and achievements - of 85 people who preferred home or a palliative care unit, 19 (25%) achieved their first preference. Conclusion: Although home is the most common first preference, it is polarising and for 16% it is the least preferred. Inpatient palliative care unit emerges as the second most preferred place, is rarely least preferred, and yet was often not achieved for those who wanted to die there. Factors affecting stated preferences and met preferences differ. Available services, notably community support and palliative care units, require expansion. Contrasting actual place of death with capacity for meeting patient and family needs may be a better quality indicator than simply 'achieved preferences'

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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The International Bathymetric Chart of the Arctic Ocean Version 4.0

Funder: The Nippon Foundation of Japan, grant Seabed 2030Funder: Open access funding provided by Stockholm UniversityAbstract: Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 × 200 m versus 500 × 500 m) and with individual depth soundings constraining three times more area of the Arctic Ocean (∼19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises ∼14.3% in Ver. 4.0 compared to ∼5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

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

Palliative care for advanced renal disease:A summary of the evidence and future direction

Background: Patients with end-stage kidney disease can have a significant symptom burden with complex co-morbidities. Compounding this is the choice between dialysis and conservative management. Need for supportive and palliative care: For individuals with end-stage kidney disease, palliative care can provide support with symptom management, advance care planning and psychological support and education for both patients and their families. Optimum management may be achieved through collaboration between renal and palliative care professionals, combining their different skills in addressing symptom and medication management. Palliative and supportive care must be patient-centred to be effective. Multidisciplinary cross-organisational input is central to address the complex care needs of these patients, particularly for those in the community. What is known/what is not known: There is growing awareness of the need for research into the palliative care needs of those with end-stage kidney disease. Research has shown that patients receiving dialysis may prioritise quality of life over survival time, partly due to the constraints that they feel dialysis imposes on them. Systematic study of those opting for a conservative management pathway rather than dialysis is beginning to happen. Research implications: Research is required into what underpins the preferences and priorities of patients with end-stage kidney disease to provide them with the best palliative and supportive care. Policy and practice: As more patients opt to follow the conservative pathway for their advanced renal disease, a change in service provision is required, with greater regular inclusion of palliative and supportive needs to address the gap in the care provision for this growing group. </jats:sec

Measures to assess commonly experienced symptoms for people with dementia in long-term care settings:A systematic review

Study details for included studies – population, setting, and who the measure was administered by. (DOCX 24 kb