The role of the clinical nurse specialist in stoma care: A modified Delphi consensus.

INTRODUCTION: The role of the clinical nurse specialist is complex but is defined differently across the world. The role of clinical nurse specialist stoma care is undefined and it is uncertain what aspects of the role are included in the general day-to-day working role. AIMS: The aim was to gain consensus opinion to answer the research question: 'What is the role of the clinical nurse specialist in stoma care?' DESIGN: Delphi consensus. METHODS: Previous data gained from a scoping review and expert consultation was utilized to form role statements. At a UK conference the 13 statements and 173 sub-categories were voted upon. Consensus was agreed if 75% of voters voted agree or strongly agree. Two stages of voting occurred with results from the first vote being shared in the second voting session. RESULTS: All 13 statement and most (150/193) statement sub-categories reached consensus, with 20 sub-categories added during voting session one. CONCLUSIONS: The four pillars of advanced practice were met by the 13 statements with clinical and education reaching higher consensus and agreement than leadership/management and research. The results of the consensus study provide a clearer articulation of the clinical nurse specialist stoma care role, which is complex and multifaceted which has not been described previously. IMPLICATIONS FOR PRACTICE: Consideration of role evolution is made possible, to gain a greater expertise in the scope of practice it is necessary to include prescribing, management and research which could improve service delivery and optimize patient outcomes. There was no patient or public contribution, which in hindsight would have potentially improved the process but it was considered that patients might not recognize the full role of the nurse, understanding only aspects of the role that were patient-centred. PATIENT OR PUBLIC CONTRIBUTION: No patients or public were involved in any aspect of this paper-in hindsight this might have been useful.

The role of the clinical nurse specialist in stoma care: a scoping review.

AIM: Rapidly evolving roles in nursing require exploration and description. This review aims to examine the role of the clinical nurse specialist (CNS) in stoma care from the UK perspective. DESIGN: A scoping review was undertaken using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data were synthesised using content analysis to derive meaning units and themes. DATA SOURCES: Three electronic databases were used to conduct the search: Embase, AMED and Ovid Medline. Additional sources identified through the reference lists of included studies and guidelines were also included. METHODS: Two reviewers undertook the search for articles that described the role of the stoma care CNS in the UK. Any disagreements were to be resolved through discussion. RESULTS: Seven papers met the eligibility criteria. Analysis resulted in 184 unique meaning units. Meaning units were grouped into themes reflecting the four pillars of advanced practice: advanced clinical practice; leadership; facilitation of education and learning; and evidence, research and development. The fewest meaning units were attributed to the evidence theme (n=13) and the most related to advanced clinical practice (n=107) such as having specialist knowledge and skills to manage complications. CONCLUSION: The stoma care CNS role reflects the four pillars of advanced practice. These practitioners are valuable, carrying out a complex role that involves high-level, specialist decision-making skills. The results from this scoping review could be useful in service development; they will be used to inform the Association of Stoma Care Nurses UK modified Delphi consensus to examine the views of stoma care CNS practitioners.

Hermit crabs (Pagurus bernhardus) use visual contrast in self-assessment of camouflage.

Animals can make use of camouflage to reduce the likelihood of visual detection or recognition and thus improve their chances of survival. Background matching, where body colouration is closely matched to the surrounding substrate, is one form of camouflage. Hermit crabs have the opportunity to choose their camouflage independently of body colouration as they inhabit empty gastropod shells, making them ideal to study their choice of camouflage. We used 3D-printed artificial shells of varying contrasts against a grey substrate to test whether hermit crabs prefer shells that they perceive as less conspicuous. Contrast-minimising shells were chosen for Weber contrasts stronger than -0.5. However, in looming experiments, animals responded to contrasts as weak as -0.2, indicating that while they can detect differences between shells and the background, they are only motivated to move into those shells when the alternatives contrast strongly. This suggests a trade-off between camouflage and vulnerability introduced by switching shells.

Stoma care in a time of financial pressures: can we cut the costs?

Andrew Bird, Lead Stoma Care Nurse Specialist, Colorectal and Stoma Care, Surgery Division, Queen's Medical Centre Campus, Nottingham University Hospitals NHS Trust, Andrew.Bird@nuh.nhs.uk.

Clinical implementation of a knowledge based planning tool for prostate VMAT.

BACKGROUND: A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. METHODS: A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. RESULTS: Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. CONCLUSIONS: The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

Application of an Integrated Blowout Model System, OILMAP DEEP, to the Deepwater Horizon (DWH) Spill.

OILMAP DEEP, an integrated system of models (pipeline release, blowout plume, dispersant treatment, oil droplet size distribution, and fountain and intrusion), was applied to the Deepwater Horizon (DWH) oil spill to predict the near field transport and fate of the oil and gas released into the northeastern Gulf of Mexico. The model included multiple, time dependent releases from both the kink and riser, with the observed subsurface dispersant treatment, that characterized the DWH spill and response. The blowout model predictions are in good agreement with the available observations for plume trapping height and the major characteristics of the intrusion layer. Predictions of the droplet size distribution are in good agreement with the limited in situ Holocam observations. Model predictions of the percentage of oil retained in the intrusion layer are consistent with independent estimates based on field observations.

In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA.

Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P < 0.04). Furthermore, transgene integration has been confirmed by sequencing in the majority of the mice treated with both vectors. Targeted alleles were 4.6-fold more common in livers of mice with GSD Ia, as compared with normal littermates, at 8 months following vector administration (P < 0.02). This suggests a selective advantage for vector-transduced hepatocytes following ZFN-mediated integration of the G6Pase vector. A short-term experiment also showed that 3-month-old mice receiving the ZFN had significantly-improved biochemical correction, in comparison with mice that received the donor vector alone. These data suggest that the use of ZFNs to drive integration of G6Pase at a safe harbor locus might improve vector persistence and efficacy, and lower mortality in GSD Ia.

Synergistic Efficacy from Gene Therapy with Coreceptor Blockade and a ß2-Agonist in Murine Pompe Disease.

Pompe disease (glycogen storage disease type II; acid maltase deficiency) is a devastating myopathy resulting from acid α-glucosidase (GAA) deficiency in striated and smooth muscle. Despite the availability of enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA), the limitations of ERT have prompted the preclinical development of gene therapy. Gene therapy has the advantage of continuously producing GAA, in contrast to ERT, which requires frequent injections of rhGAA. An adeno-associated viral (AAV) vector containing a muscle-specific promoter, AAV-MHCK7hGAApA, achieved high GAA expression in heart and skeletal muscle in mice with Pompe disease. However, elevated GAA activity was not sufficient to completely clear accumulated glycogen in skeletal muscle. The process of glycogen clearance from lysosomes might require improved trafficking of GAA to the lysosomes in skeletal muscle, previously achieved with the ß(2)-agonist clenbuterol that enhanced glycogen clearance in skeletal muscle without increasing GAA activity. Glycogen clearance was clearly enhanced by treatment with a nondepleting anti-CD4 monoclonal antibody (anti-CD4 mAb) along with muscle-specific GAA expression in cardiac muscle, but that treatment was not effective in skeletal muscle. Furthermore, anti-CD4 mAb treatment along with clenbuterol achieved synergistic therapeutic efficacy in both cardiac and skeletal muscle. This triple therapy increased both muscle strength and weight gain. Overall, triple therapy to enhance GAA trafficking and to suppress immune responses significantly improved the efficacy of muscle-targeted gene therapy in murine Pompe disease.

Enhanced efficacy from gene therapy in Pompe disease using coreceptor blockade.

Enzyme replacement therapy (ERT) is the standard-of-care treatment of Pompe disease, a lysosomal storage disorder caused by deficiency of acid α-glucosidase (GAA). One limitation of ERT with recombinant human (rh) GAA is antibody formation against GAA. Similarly, in adeno-associated virus (AAV) vector-mediated gene transfer for Pompe disease, development of antibodies against the GAA transgene product and the AAV vector prevents therapeutic efficacy and vector readministration, respectively. Here a nondepleting anti-CD4 monoclonal antibody (mAb) was administrated intravenously prior to administration of an AAV2/9 vector encoding GAA to suppress anti-GAA responses, leading to a substantial reduction of anti-GAA immunoglobulins, including IgG1, IgG2a, IgG2b, IgG2c, and IgG3. Transduction efficiency in liver with a subsequent AAV2/8 vector was massively improved by the administration of anti-CD4 mAb with the initial AAV2/9 vector, indicating a spread of benefit derived from control of the immune response to the first AAV2/9 vector. Anti-CD4 mAb along with AAV2/9-CBhGAApA significantly increased GAA activity in heart and skeletal muscles along with a significant reduction of glycogen accumulation. Taken together, these data demonstrated that the addition of nondepleting anti-CD4 mAb with gene therapy controls humoral immune responses to both vector and transgene, resulting in clear therapeutic benefit in mice with Pompe disease.

Adjunctive ß2-agonist treatment reduces glycogen independently of receptor-mediated acid α-glucosidase uptake in the limb muscles of mice with Pompe disease.

Enzyme or gene replacement therapy with acid α-glucosidase (GAA) has achieved only partial efficacy in Pompe disease. We evaluated the effect of adjunctive clenbuterol treatment on cation-independent mannose-6-phosphate receptor (CI-MPR)-mediated uptake and intracellular trafficking of GAA during muscle-specific GAA expression with an adeno-associated virus (AAV) vector in GAA-knockout (KO) mice. Clenbuterol, which increases expression of CI-MPR in muscle, was administered with the AAV vector. This combination therapy increased latency during rotarod and wirehang testing at 12 wk, in comparison with vector alone. The mean urinary glucose tetrasaccharide (Glc4), a urinary biomarker, was lower in GAA-KO mice following combination therapy, compared with vector alone. Similarly, glycogen content was lower in cardiac and skeletal muscle following 12 wk of combination therapy in heart, quadriceps, diaphragm, and soleus, compared with vector alone. These data suggested that clenbuterol treatment enhanced trafficking of GAA to lysosomes, given that GAA was expressed within myofibers. The integral role of CI-MPR was demonstrated by the lack of effectiveness from clenbuterol in GAA-KO mice that lacked CI-MPR in muscle, where it failed to reverse the high glycogen content of the heart and diaphragm or impaired wirehang performance. However, the glycogen content of skeletal muscle was reduced by the addition of clenbuterol in the absence of CI-MPR, as was lysosomal vacuolation, which correlated with increased AKT signaling. In summary, ß2-agonist treatment enhanced CI-MPR-mediated uptake and trafficking of GAA in mice with Pompe disease, and a similarly enhanced benefit might be expected in other lysosomal storage disorders.

Competency in managing care in epidural analgesia.

BACKGROUND: Epidural analgesia (EA) is effective in providing postoperative pain relief, but has potential complications. An audit was carried out to measure the knowledge, skills and adherence to protocols of nurses deemed competent to care for patients receiving EA. METHOD: This audit assessed the recording of observations, staff practices and knowledge against the trust's policy for EA care. RESULTS: All observation charts examined (n = 16) were incomplete. Nurses (n = 9) scored a mean of 24.4 out of a possible 28 points in the observational assessment. Six (66%) questionnaires were returned. The nurses scored a mean of 75% on the questionnaires. CONCLUSION: The results from the audit should be viewed with caution as the amount of data collected was small, but suggest there is a need for changes to the protocol for epidural observations and the associated teaching programme. Further results that can be more easily generalised.

Enhanced gene expression of systemically administered plasmid DNA in the liver with therapeutic ultrasound and microbubbles.

Ultrasound-mediated delivery (USMD) of novel therapeutic agents in the presence of microbubbles is a potentially safe and effective method for gene therapy offering many desired characteristics, such as low toxicity, potential for repeated treatment, and organ specificity. In this study, we tested the capability of USMD to improve gene expression in mice livers using glycogen storage disease Type Ia as a model disease under systemic administration of naked plasmid DNA. Image-guided therapeutic ultrasound was used in two studies to provide therapeutic ultrasound to mice livers. In the first study, involving wild-type mice, control animals received naked plasmid DNA (pG6Pase 150 µg) via the tail vein, followed by an infusion of microbubbles; the treated animals additionally received therapeutic ultrasound (1 MHz). Following the procedure, the animals were left to recover and were subsequently euthanized after 2 d and liver samples were extracted. Reverse transcription polymerase chain reaction (RT-PCR) assays were performed on the samples to quantify mRNA expression. In addition, Western blot assays of FLAG-tagged glucose-6-phosphatase (G6Pase) were performed to evaluate protein expression. Ultrasound-exposed animals showed a 4-fold increase in G6Pase RNA in the liver, in comparison with control animals. Furthermore, results from Western blot analysis demonstrated a 2-fold increased protein expression in ultrasound-exposed animals after two days ( p < 0.05). A second pilot study was performed with G6Pase knockout mice, and the animals were monitored for correction of hypoglycemia over a period of 3 weeks before tissue analysis. The RT-PCR assays of samples from these animals demonstrated increased G6Pase RNA in the liver following ultrasound treatment. These results demonstrate that USMD can increase gene expression of systemically injected naked pDNA in the liver and also provide insight into the development of realistic approaches that can be translated into clinical practice.

Adjunctive ß2-agonists reverse neuromuscular involvement in murine Pompe disease.

Pompe disease has resisted enzyme replacement therapy with acid α-glucosidase (GAA), which has been attributed to inefficient cation-independent mannose-6-phosphate receptor (CI-MPR) mediated uptake. We evaluated ß2-agonist drugs, which increased CI-MPR expression in GAA knockout (KO) mice. Clenbuterol along with a low-dose adeno-associated virus vector increased Rotarod latency by 75% at 4 wk, in comparison with vector alone (P<2×10(-5)). Glycogen content was lower in skeletal muscles, including soleus (P<0.01), extensor digitorum longus (EDL; P<0.001), and tibialis anterior (P<0.05) following combination therapy, in comparison with vector alone. Glycogen remained elevated in the muscles following clenbuterol alone, indicating an adjunctive effect with gene therapy. Elderly GAA-KO mice treated with combination therapy demonstrated 2-fold increased wirehang latency, in comparison with vector or clenbuterol alone (P<0.001). The glycogen content of skeletal muscle decreased following combination therapy in elderly mice (P<0.05). Finally, CI-MPR-KO/GAA-KO mice did not respond to combination therapy, indicating that clenbuterol's effect depended on CI-MPR expression. In summary, adjunctive ß2-agonist treatment increased CI-MPR expression and enhanced efficacy from gene therapy in Pompe disease, which has implications for other lysosomal storage disorders that involve primarily the brain.