Pressure injury prevalence in Australian intensive care units: A secondary analysis.

BACKGROUND: Pressure injuries (PIs) are an enduring problem for patients in the intensive care unit (ICU) because of their vulnerability and numerous risk factors. METHOD: This study reports Australian data as a subset of data from an international 1-day point prevalence study of ICU-acquired PI in adult patients. Patients aged 18 years or older and admitted to the ICU on the study day were included. The outcome measure was the identification of a PI by direct visual skin assessment on the study day. Data collected included demographic data and clinical risk factors, PI location and stage, and PI prevention strategies used. Descriptive statistics were used to describe PI characteristics, and odds ratios (ORs) were used to identify factors associated with the development of a PI. RESULTS: Data were collected from 288 patients from 16 Australian ICUs. ICU-acquired PI prevalence was 9.7%, with 40 PIs identified on 28 patients. Most PIs were of stage 1 and stage 2 (26/40, 65.0%). Half of the ICU-acquired PIs were found on the head and face. The odds of developing an ICU-acquired PI increased significantly with renal replacement therapy (OR: 4.25, 95% confidence interval [CI]: 1.49-12.11), impaired mobility (OR: 3.13, 95% CI: 1.08-9.12), fastest respiratory rate (OR: 1.05 [per breath per minute], 95% CI: 1.00-1.10), longer stay in the ICU (OR: 1.04 [per day], 95% CI: 1.01-1.06), and mechanical ventilation on admission (OR: 0.36, CI: 0.14-0.91). CONCLUSION: This study found that Australian ICU-acquired PI prevalence was 9.7% and these PIs were associated with many risk factors. Targeted PI prevention strategies should be incorporated into routine prevention approaches to reduce the burden of PIs in the Australian adult ICU patient population.

Clinical coaches and patient safety - Just in time: A descriptive exploratory study.

Patient safety in hospitals is a key priority. Clinical coaches who educate, support and coach staff to deliver safe, high quality care, are ideally placed to positively influence patient safety. AIM: This study aimed to understand how clinical coaches in an education role, manage risk and support patient safety at the point of care. BACKGROUND: Patient safety has developed from a find and fix reactive model towards an approach which focuses on human performance, aiming to understand how individuals adapt and respond in complex systems to ensure 'things go right'. Clinical coaches working as educators at the point of care, are uniquely placed to ensure 'things go right', supporting staff to anticipate and proactively respond to emerging issues, particularly when complex practice situations change unexpectedly. Clinical coach experiences of intervening 'just in time' to prevent errors incidents or omissions occurring at the point of care is unknown. DESIGN: This was a descriptive exploratory study conducted with registered nurses working in the role of clinical coach (n = 29). METHODS: Study data were collected through a purposefully designed survey. RESULTS: Clinical coaches intervened 'just in time' across a variety of clinical situations including medication errors, clinical procedures, documentation, assessment skills and clinical handover. Lower skill mix, higher patient acuity and the commencement of new staff influenced clinical coach 'just in time' interventions. Most of the clinical coaches had intervened with both junior and senior members of staff. Overall, clinical coaches spent up to 3-4 h every day proactively managing risk across a variety of clinical situations and staff. CONCLUSIONS: Clinical coaches play an important role in ensuring patient safety by regularly intervening 'just in time' to prevent errors, omissions, or incidents from occurring at the point of care. The clinical coach role, which educates and supports staff to deliver safe, high quality care, makes a valuable contribution towards patient safety.

Increased Tumor Penetration of Single-Domain Antibody-Drug Conjugates Improves In Vivo Efficacy in Prostate Cancer Models.

Targeted delivery of chemotherapeutics aims to increase efficacy and lower toxicity by concentrating drugs at the site-of-action, a method embodied by the seven current FDA-approved antibody-drug conjugates (ADC). However, a variety of pharmacokinetic challenges result in relatively narrow therapeutic windows for these agents, hampering the development of new drugs. Here, we use a series of prostate-specific membrane antigen-binding single-domain (Humabody) ADC constructs to demonstrate that tissue penetration of protein-drug conjugates plays a major role in therapeutic efficacy. Counterintuitively, a construct with lower in vitro potency resulted in higher in vivo efficacy than other protein-drug conjugates. Biodistribution data, tumor histology images, spheroid experiments, in vivo single-cell measurements, and computational results demonstrate that a smaller size and slower internalization rate enabled higher tissue penetration and more cell killing. The results also illustrate the benefits of linking an albumin-binding domain to the single-domain ADCs. A construct lacking an albumin-binding domain was rapidly cleared, leading to lower tumor uptake (%ID/g) and decreased in vivo efficacy. In conclusion, these results provide evidence that reaching the maximum number of cells with a lethal payload dose correlates more strongly with in vivo efficacy than total tumor uptake or in vitro potency alone for these protein-drug conjugates. Computational modeling and protein engineering can be used to custom design an optimal framework for controlling internalization, clearance, and tissue penetration to maximize cell killing. SIGNIFICANCE: A mechanistic study of protein-drug conjugates demonstrates that a lower potency compound is more effective in vivo than other agents with equal tumor uptake due to improved tissue penetration and cellular distribution.

Diverse human VH antibody fragments with bio-therapeutic properties from the Crescendo Mouse.

We describe the 'Crescendo Mouse', a human VH transgenic platform combining an engineered heavy chain locus with diverse human heavy chain V, D and J genes, a modified mouse Cγ1 gene and complete 3' regulatory region, in a triple knock-out (TKO) mouse background devoid of endogenous immunoglobulin expression. The addition of the engineered heavy chain locus to the TKO mouse restored B cell development, giving rise to functional B cells that responded to immunization with a diverse response that comprised entirely 'heavy chain only' antibodies. Heavy chain variable (VH) domain libraries were rapidly mined using phage display technology, yielding diverse high-affinity human VH that had undergone somatic hypermutation, lacked aggregation and showed enhanced expression in E. coli. The Crescendo Mouse produces human VH fragments, or Humabody® VH, with excellent bio-therapeutic potential, as exemplified here by the generation of antagonistic Humabody® VH specific for human IL17A and IL17RA.

Perceptions of the impact of introducing administrative support for nurse unit managers: A qualitative evaluation.

AIM: To evaluate the impacts of introducing administrative support for nurse unit managers. BACKGROUND: Increased administrative load for nurse unit managers causes role stress and reduced opportunities for clinical leadership (state-wide review, Queensland, Australia). In response, a health organisation implemented a clerical 'Nurse Unit Manager Support Officer' position. METHODS: Qualitative descriptive evaluation, convenience sample (37 nurse unit managers and NUM Support Officers) and focus groups (13) provided data that were thematically analysed. RESULTS: Six impacts were identified: (a) improved nurse unit manager well-being; (b) more time to undertake clinical leadership; (c) greater efficiencies in finance, payroll and HR processes; (d) improved capacity for strategic leadership; (e) increased staff satisfaction and improved unit culture; and (f) improved succession planning. CONCLUSION: Findings reveal significant gains and benefits from the introduction of administrative support for the nurse unit manager role for the nurse unit manager and the units they manage. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse unit manager role stress can negatively impact organisational climate, performance outcomes, staff satisfaction and retention. Health organisations need to implement strategies to reduce the administrative burden for nurse unit managers. The introduction of administrative support frees up time for nurse unit managers to engage in clinical leadership, positively impacting organisational climate, performance outcomes, and staff satisfaction and retention.

The use of port-a-caths in adult patients with Lysosomal Storage Disorders receiving Enzyme Replacement Therapy-one centre experience.

Port-a-cath is a widely used device in patients with long-term venous access demand such as frequent or continuous administration of medications such as Enzyme Replacement Therapy (ERT), chemotherapy delivery, blood transfusions, blood products, and fluids. Patients with Lysosomal Storage Diseases (LSDs) often require recurrent courses of ERT. We reviewed our experience of using port-a-caths in patients with LSDs with the focus on challenges and complications associated with these catheters. Among 245 adult patients who were treated with ERT, twenty patients (8.2%) had a port-a-cath inserted due to poor venous access. Six patients were using their first port whereas five other patients had their port-a-caths replaced at least once. The remaining six patients had inactive port-a-caths. The majority of patients with active port-a-caths never missed more than one consecutive infusion, although one patient missed 2 consecutive infusions whilst on holiday. We identified significant gaps in patients' and their families' understanding of the management of port-a-caths and risks associated with them. It resulted in producing a leaflet and designing an educational program for our LSD patients.

Back to the future: A practice led transition program from Assistant in Nursing to Enrolled Nurse.

Continuing professional development is an essential element in professional nursing practice. In our Hospital and Health service, a gap in existing nursing pathways was identified for Assistants in Nursing (AINs), who wished to further their career in nursing and progress to Enrolled Nurse (EN). There is also little in the literature that addresses Assistants in Nursing wishing to progress their career to Enrolled Nurses. This article describes a quality improvement project designed to address this gap. The project was a collaborative venture between a Queensland Hospital and Health Service and an Institute of Tertiary and Further Education (TAFE). The focus was on creating a flexible career path for Assistants in Nursing, wishing to become Enrolled Nurses. The project resulted in the Diploma of Nursing program (theory and practice) being delivered within the hospital setting by nurse educators and clinical nurse consultants. This is unusual in that the program is normally delivered in the tertiary setting, by academic staff from the Institute of Further Education. Program implementation is described along with the challenges encountered. Outcomes from the project were: 78% completion rate; 100% employment on completion of their course of study; and 18% progressing to further their education such as Advance Enrolled Nurse or Registered Nurse. Student satisfaction regarding the program was also positive. The initiative established a local career path for Assistants in Nursing wishing to progress to Enrolled Nurse. This quality project demonstrates that collaborative ventures between the tertiary sector and hospital and health services, can create innovative flexible solutions for staff wishing to further their career in nursing.

A LIF/Nanog axis is revealed in T lymphocytes that lack MARCH-7, a RINGv E3 ligase that regulates the LIF-receptor.

Nanog is a stem cell transcription factor required for self-renewal and for maintaining pluripotency, and Nanog itself is regulated at least in part by leukaemia inhibitory factor (LIF)--a pluripotent cytokine of the IL6 family. MARCH-7 is an E-3 ligase linked to regulation of the LIF-receptor in T lymphocytes and T cells from mice that lack expression of MARCH-7 are hyper-responsive to activation signals and show a five-fold increase in LIF activity. Here we ask, does MARCH-7 influence the expression profile of Nanog during the synchronized entry of T cells into the cell cycle? We discovered that lack of MARCH-7 was permissive for Nanog expression at both transcript and protein levels during G1/S: moreover, addition of exogenous LIF to the MARCH-7 null cells caused a further 13-fold induction of Nanog; other measured transcripts including TGFß, p53 and STAT3 were relatively unchanged. Since lack of MARCH-7 altered responsiveness to activation signals we sought evidence for pre-existing regulatory miR's that might correlate with MARCH-7 gene dose using head-to-head comparisons between MARCH-7 null, heterozygous and wt spleen cells. 34 miRs were found including miR-346 that is known to target LIF transcripts and miR-346 is one of 16 miRs differentially expressed between hESCs and induced hiPSCs. Of the 34 miRs, 12 were known to be temporally regulated in embryonic nerve cells. In summary, in the absence of MARCH-7 a new signaling pathway is unmasked that involves Nanog expression in the T cell lineage. This is the first demonstration that T cells retain responsiveness to a LIF/Nanog axis and that this axis is linked to MARCH-7.

Corneal confocal microscopy: a novel noninvasive means to diagnose neuropathy in patients with Fabry disease.

Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal aesthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS) and heat-induced pain (HIP) were only significantly increased in males on ERT (P < 0.01). However, corneal sensation assessed with NCCA was significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QST and CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

Treg versus Th17 lymphocyte lineages are cross-regulated by LIF versus IL-6.

Within the immune system there is an exquisite ability to discriminate between "self" and "non-self" that is orchestrated by T lymphocytes. Discriminatory pathways guide differentiation of these lymphocytes into either regulatory (Treg) or effector (Teff) T cells, influenced by cues from the naïve T cell's immediate micro-environment as it responds to cognate antigen. Reciprocal pathways may lead to commitment of naïve T cells into either the protective tolerance-promoting Treg, or to the pro-inflammatory Th17 effector phenotype. Primary activation of CD4(+) lymphocytes stimulates their release of leukemia inhibitory factor (LIF), and Treg continue to release LIF in response to antigen, implying a role for LIF in tolerance. In contrast, interleukin- 6 (IL-6), although very closely related to LIF, promotes maturation of Th17 cells. Here we show that LIF and IL-6 behave as polar opposites in promoting commitment to the Treg and Th17 lineages. Unlike IL6, LIF supported expression of Foxp3, the Treg lineage transcription factor, and LIF opposed IL6 by suppressing IL-6-induced IL-17A protein release. In striking contrast, we found that IL6 effectively inhibited LIF signalling, repressing transcription of the LIF receptor gp190, and strongly inducing axotrophin/MARCH-7, a novel E3 ubitquitin ligase that we discovered to be active in degradation of gp190 protein. In vivo, anti-LIF treatment reduced donor-specific Treg in recipients of foreign spleen cells. Conversely, a single dose of biodegradable LIF nanoparticles, targeted to CD4, successfully manipulated the LIF/IL6 axis towards development of donor-specific Foxp3(+) Treg. The implications for therapy are profound, harnessing endogenous immune regulation by paracrine delivery of LIF to CD4(+) cells in vivo.

Studies on monitoring and tracking genetic resources: an executive summary.

The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information.

Evidence for functional inter-relationships between FOXP3, leukaemia inhibitory factor, and axotrophin/MARCH-7 in transplantation tolerance.

In an ex vivo mouse model, regulatory transplantation tolerance is not only linked to Foxp3, but also to release of leukaemia inhibitory factor (LIF) and to expression of axotrophin (also known as MARCH-7), a putative ubiquitin E3 ligase associated with feedback control of T cell activation and of T cell-derived LIF. Given this coordinate correlation with tolerance, we now ask if Foxp3 expression is influenced by LIF or by axotrophin. In spleen cells from allo-rejected mice we found that exogenous LIF reduced interferon gamma release in response to donor antigen by 50%, but LIF had no direct effect on levels of Foxp3 protein in allo-primed cells that were either tolerant, or aggressive, for donor antigen. However, we did find an effect of axotrophin on Foxp3: in the axotrophin null mouse, thymic Foxp3 transcripts were reduced compared to axotrophin wildtype littermates. To test whether these findings in the mouse were of potential significance in man we measured transcript levels of axotrophin and LIF in peripheral blood cell samples collected for a recently published clinical study concerning haematopoietic stem cell recipients. In controls, human peripheral blood CD4+CD25+cells contained significantly more FOXP3 and axotrophin than CD4+CD25-cells. In bone marrow autograft recipients, where peripheral blood cell samples directly represent both the grafted tissue and the immune response, both FOXP3 and axotrophin negatively correlated with graft versus host disease (GVHD). These data suggest that (i) thymic Foxp3+T cell development is influenced by axotrophin; and (ii) clinical auto-GVHD inversely correlates with axotrophin transcript expression as has been previously reported for FOXP3.

INCAP country supplement for Belize 2000

The Report explains the significant contribution to food and nutrition security in Belize

INCAP Belize Annual Report

This report is about the Food and Nutrition Policy and Plan for Belize