How does specialist nursing contribute to HIV service delivery across England?

Objectives: This study aimed to examine what specialist nursing contributes to HIV service delivery across England and how it could be optimized. Methods: A three part multi-method qualitative study involving: (1) interviews with 19 stakeholders representing professional or service user groups; (2) interviews with nurse/physician pairs from 21 HIV services; (3) case studies involving site visits to 5 services. A framework analysis approach was used to manage and analyse the data. Results: There was substantial variability in specialist nursing roles and the extent of role development. Most hospital-based HIV nurses (13/19) were running nurse-led clinics, primarily for stable patients with almost half (6/13) also managing more complex patients. Role development was supported by non-medical prescribing, a robust governance framework and appropriate workload allocation. The availability and organisation of community HIV nursing provision determined how services supported vulnerable patients to keep them engaged in care. Four service models were identified. Conclusion: There is scope for providing a greater proportion of routine care through nurse-led clinics. HIV community nursing can influence health outcomes for vulnerable patients, but provision is variable. With limited financial resources, services may need to decide how to deploy their specialist nurses for best effect

A workforce in jeopardy - identifying the challenges of ensuring a sustainable advanced HIV nursing workforce.

Introduction: HIV services in England face substantial challenges arising from financial pressures and changes to commissioning. A sustainable HIV specialist nursing workforce will be vital to enable them to respond to those challenges. This paper examines the current workforce situation in HIV services across the country. Methods: This mixed method study involved semi-structured interviews with 19 key stakeholders and with 44 nurses / physicians from 21 purposively selected HIV services across England. Data were interpreted using a framework analysis approach. Findings: 'Building a career in HIV nursing' identified problems associated with retention and recruitment. Changes in commissioning are disrupting common career routes from sexual health to HIV nursing and a perceived lack of clear career pathway was seen as a barrier to recruitment. 'Developing a specialist workforce' explored professional development of the current workforce which was hampered by poor access to funding or study time for advanced study, and the absence of an HIV-specific advanced nursing qualification. Conclusion: The HIV nursing workforce, which provides an increasing proportion of HIV care, is facing serious recruitment and retention challenges. A strategic approach to workforce development and training is essential to overcome systemic barriers and secure the next generation of skilled practitioners

Developing and testing a community-based nursing intervention to improve engagement of HIV Patients in care and treatment (Conect) (Abstract only)

The health outcomes now achievable for people living with HIV require long-term engagement with treatment and care. This is problematic for a significant minority. Disengagement from HIV services is strongly associated with poor health outcomes and reduced life expectancy. It accounts for a large proportion of avoidable hospital admissions and has considerable public health implications associated with onward transmission. Preventing disengagement is a major challenge for HIV services. Those who disengage from care commonly have complex needs and a range of psychosocial problems. This indicates the need for reengagement interventions that take an individualised approach. The aim of this project is to develop and test a community-delivered nursing intervention designed to prevent individuals disengaging from HIV treatment and care. The project involves development of a reengagement intervention and delivery of the intervention through a pilot community HIV nursing service. The intervention is structured around a strengths-based approach and theoretically based on the Behaviour Change Wheel. A process and outcome evaluation will establish effectiveness and acceptability of the intervention. A structured and theoretically informed intervention has the potential to make a significant contribution to reducing disengagement rates in this population. Establishing a pilot service to deliver this intervention and conducting a comprehensive evaluation will enable us to assess its effectiveness and identify the key determinants of success to inform transferability of this approach

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

Advanced Nursing contribution to HIV care

The ANCHIVS study was a national project to examine the contribution of specialist nursing to the delivery of HIV services in England. It was undertaken in response to the urgent need to review the models of HIV care delivery and adapt them to address the changing health needs of those living with HIV care within the current financial constraints of the NHS. The study was undertaken in 2014-15 with data collection taking place between April 2014 -March 2015. This archive contains all the data for this project in the form of transcribed anonymised interviews. The data for this study are contained in three folders, each of which relates to a separate stage of the project. Documents have all been saved as rtf for archiving purposes. Stage - semi-structured interviews with key stakeholders Stage 2 - semi-structured interviews with nurse-doctor pairs. Stage 3 - case studies of five stage 2 study sites. Labelling conventions. P = Physician N = Nurse C = Commissioner SU = service use

Life-history traits of a small-bodied coastal shark

The life histories of small-bodied coastal sharks, particularly carcharhinids, are generally less conservative than those of large-bodied species. The present study investigated the life history of the small-bodied slit-eye shark, Loxodon macrorhinus, from subtropical Hervey Bay, Queensland, and compared this species' biology to that of other coastal carcharhinids. The best-fit age model provided parameters of L∞=895mm total length (TL), k=0.18 and t0=-6.3 for females, and L∞=832mmTL, k=0.44 and t0=-2.6 for males. For sex-combined data, a logistic function provided the best fit, with L∞=842mmTL, k=0.41 and α=-2.2. Length and age at which 50% of the population was mature was 680mmTL and 1.4 years for females, and 733mmTL and 1.9 years for males. Within Hervey Bay, L. macrorhinus exhibited an annual seasonal reproductive cycle, producing an average litter of 1.9±0.3s.d. With the exception of the low fecundity and large size at birth relative to maximum maternal TL, the life-history traits of L. macrorhinus are comparable to other small-bodied coastal carcharhinids, and its apparent fast growth and early maturation contrasts that of large-bodied carcharhinids

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease