Low-dose mesenchymal stem cell therapy for discogenic pain: safety and efficacy results from a 1-year feasibility study.

Aim: To evaluate safety and efficacy of low dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for treatment of disc degeneration resulting in low back pain (LBP). Methods: Nine participants with chronic LBP originating from single-level lumbar disc disease underwent intradiscal injection of 10 million ADMSCs with optional repetition after 6 months. Results: No unexpected or serious adverse events were recorded. Seven (78%) of participants reported reductions in pain 12 months after treatment. Five (56%) reported increased work capacity. Three (33%) reduced analgesic medication. Improvements in EQ-5D and Oswestry disability index results were observed. MRI demonstrated no further disc degeneration and improvements to annular fissures and disc protrusions. Conclusion: This study provides initial evidence of safety and efficacy of ADMSCs for discogenic LBP.

Results of a Pilot Study on the Safety and Early Efficacy of Novel Polymethyl Methacrylate Microspheres and a Hyaluronic Acid Device for the Treatment of Low Back Pain Caused by Degenerative and Diseased Intervertebral Discs of the Lumbar Spine.

Background Low back pain (LBP) costs the healthcare system billions of dollars each year. Intervertebral disc (IVD) degeneration is a significant cause of LBP, due to structural defects, biomechanical instability, and inflammation. First-line therapy for patients with LBP includes physical therapy, medication, and steroid injections. DiscSealTM was developed to provide patients who are refractory to first-line therapy with a minimally invasive treatment alternative to invasive surgical procedures. The product is a combination of poly-methyl methacrylate (PMMA) microspheres in hyaluronic acid (HA) that is injected under modified discography into the IVD. Methods Two pain specialist centers in Australia recruited eligible participants who were followed up for 180 days post-procedure. The procedure was conducted using a modified discography technique. Low back and leg pain was reported using the Visual Analogue Scale (VAS) while other endpoints included were Oswestry Disability Index (ODI), Clinician and Patient Global Impact of Change, and Patient Rating of Overall Health Status. The general analytical approach for all endpoints was descriptive in nature and 95% confidence intervals of means were estimated. Results The pilot study achieved its primary objective which was an absence of peri-treatment or post-treatment device-related Serious Adverse Events (SAE) during the first 90 days. There were no device-related serious adverse events recorded throughout the study. The mean LBP percentage change from baseline at 90 and 180 days was -27.0% and -42.3% respectively. The mean ODI percentage change from baseline at 90 and 180 days was -22.3 and -14.2% respectively. End of study improvements shows a 67.8% (20.83) increase in Overall Health Status, as well as positive results for Participant and Clinician Global Impact of Change. These results were achieved based on treating one diseased IVD, although 83.3% of patients were diagnosed with multiple diseased IVDs. Conclusions The results from this pilot study showed that DiscSealTM is safe and well-tolerated. Early efficacy shows that DiscSealTM may be a promising treatment option for people suffering from discogenic LBP that have not responded to first-line treatment options. A larger, statistically powered study where all diseased discs are treated should be completed to validate the promising results from this early feasibility study.

Neonatal dietitian resourcing and roles in New Zealand and Australia: A survey of current practice.

AIM: Dietitian-led implementation of evidence-based nutrition support practices improves nutrient intakes, clinical outcomes and growth, decreases length of stay and related costs, and reduces intravenous nutrition costs and prescription errors. We aimed to investigate current neonatal dietitian resourcing and roles in New Zealand and Australian neonatal units, and to compare this with dietitian workforce recommendations and previously reported survey data. METHODS: A two-part electronic survey was emailed to 50 Australasian Neonatal Dietitians Network members and other dietitians working in neonatal intensive care or special care baby units in New Zealand and Australia. The survey ran from July to October 2018. Descriptive statistics were used to examine the distribution of responses. Responses were compared with other similar surveys and British Dietetic Association workforce recommendations. RESULTS: There was an 88% response rate for Part 1. Forty-eight percent of respondents had worked in neonatology for more than 5 years. Ward rounds were attended weekly or more often by 43% of respondents. One-third regularly attended neonatal conferences or grand rounds. The majority spent less than 25% of their neonatal service allocation on teaching, developing policy or research. All respondents reported their unit had written enteral feeding guidelines. The neonatal dietitian workforce is at 23% of recommended levels. CONCLUSIONS: Australasian neonatal dietitians have great potential to add value in neonatal units which has not yet been fully realised. Funding reallocation, upskilling and on-going professional development are needed to ensure the neonatal dietitian workforce is at the recommended level to be safe, sustainable and effective.

A feasibility study to improve practice nurses' competence and confidence in providing care for mothers and infants.

BACKGROUND: Postnatal care is best provided in primary health care settings, yet Practice Nurses (PNs) lack relevant training and report difficulty in providing postnatal care. AIM: To evaluate the feasibility of a pilot educational intervention in improving PN competence and confidence to care for mothers and infants in the first postnatal year. DESIGN: A feasibility study. METHODS: PNs were recruited from selected general practices Queensland, Australia to undertake the pilot educational intervention that included a pre-intervention survey, two-day education program, program evaluation and completion of a practice journal. RESULTS: Thirteen PNs from three general practices participated, with 31% completing all study components. Evaluation of the intervention was positive and all participants reported increased confidence and competence in providing postnatal care. Following detailed consideration of feasibility (process, resource, management and scientific assessment) we propose that changes to intervention delivery and data collection should be incorporated into a larger trial.

Practice nurse involvement in the management of adults with type 2 diabetes mellitus attending a general practice: results from a systematic review.

AIM: Using the methodology of the Joanna Briggs Institute, a systematic review of current research was performed to determine if the addition of management by nurses had been more effective in improving clinical outcomes of patients with type 2 diabetes attending a general practice compared with standard care. METHODS: A three-step literature search was conducted for suitable English studies with quantitative clinical outcomes that had been published from January 1990 to May 2014. Randomised controlled trials (RCTs) were particularly sought after; however, other research designs were considered. Articles were assessed by two independent reviewers for methodological validity, prior to inclusion in the review, using standardised critical appraisal instruments from the Joanna Briggs Institute. When possible, quantitative data were pooled in statistical meta-analysis. RESULTS: Seven studies were of suitable quality and relevance for the review: these included three randomised control trials; two cluster- RCTs; a cluster, nonrandomised, controlled before-after study; and a cluster observational cohort study. These studies yield evidence that nurse management in addition to standard general practitioner care leads to modest improvements in blood pressure and total cholesterol levels in adults with type 2 diabetes attending a general practice. CONCLUSION: Meta-analysis identified modest, significant improvements amongst participants in nurse management interventions (NMIs) in the following clinical outcomes: mean SBP, mean DBP and mean total cholesterol. The majority of outcomes studied did not show any advantage to adding NMIs to general practitioner care. Two studies reported significant improvements of participants with poor control in mean haemoglobin A1c. An RCT that investigates the effect of NMIs on patients, with poor control in regard to clinical outcomes and cost effectiveness, is recommended.

Revenue effects of practice nurse-led care for chronic diseases.

OBJECTIVE: To determine the economic feasibility in Australian general practices of using a practice nurse (PN)-led care model of chronic disease management. METHODS: A cost-analysis of item numbers from the Medicare Benefit Schedule (MBS) was performed in three Australian general practices, one urban, one regional and one rural. Patients (n =254; >18 years of age) with chronic conditions (type 2 diabetes, hypertension, ischaemic heart disease) but without unstable or major health problems were randomised into usual general practitioner (GP) or PN-led care for management of their condition over a period of 12 months. After the 12-month intervention, total MBS item charges were evaluated for patients managed for their stable chronic condition by usual GP or PN-led care. Zero-skewness log transformation was applied to cost data and log-linear regression analysis was undertaken. RESULTS: There was an estimated A$129 mean increase in total MBS item charges over a 1-year period (controlled for age, self-reported quality of life and geographic location of practice) associated with PN-led care. The frequency of GP and PN visits varied markedly according to the chronic disease. CONCLUSIONS: Medicare reimbursements provided sufficient funding for general practices to employ PNs within limits of workloads before the new Practice Nurse Incentive Program was introduced in July 2012.

The feasibility, acceptability and sustainability of nurse-led chronic disease management in Australian general practice: the perspectives of key stakeholders.

This was the first Australian study investigating the acceptability, feasibility and sustainability of a nurse-led model of chronic disease management in general practice. A concurrent mixed-methods design was used within a 12-month intervention of nurse-led care in three general practices. Adult patients with type 2 diabetes, hypertension and/or stable ischaemic heart disease were randomized into nurse-led or standard care. Semi-structured interviews explored perceptions of key stakeholders towards this model including patients in the nurse-led arm, and all practice staff pre- and posttrial. The data were thematically analysed and the emergent themes were: importance of time; collaborative relationships; nurse job satisfaction, confidence and competence; patient self-management and choice. Our findings showed that nurses provided chronic disease management that was acceptable, feasible and sustainable. The collaborative involvement of doctors was intrinsic to patient acceptability of nurse-led care that facilitated job satisfaction, and therefore retention and growth within this nursing speciality.

Outcomes and opportunities: a nurse-led model of chronic disease management in Australian general practice.

The Australian government's commitment to health service reform has placed general practice at the centre of its agenda to manage chronic disease. Concerns about the capacity of GPs to meet the growing chronic disease burden has stimulated the implementation and testing of new models of care that better utilise practice nurses (PN). This paper reports on a mixed-methods study nested within a larger study that trialled the feasibility and acceptability of a new model of nurse-led chronic disease management in three general practices. Patients over 18 years of age with type 2 diabetes, hypertension or stable ischaemic heart disease were randomised into PN-led or usual GP-led care. Primary outcomes were self-reported quality of life and perceptions of the model's feasibility and acceptability from the perspective of patients and GPs. Over the 12-month study quality of life decreased but the trend between groups was not statistically different. Qualitative data indicate that the PN-led model was acceptable and feasible to GPs and patients. It is possible to extend the scope of PN care to lead the routine clinical management of patients' stable chronic diseases. All GPs identified significant advantages to the model and elected to continue with the PN-led care after our study concluded.

Reversible and oriented immobilization of ferrocene-modified proteins.

Adopting supramolecular chemistry for immobilization of proteins is an attractive strategy that entails reversibility and responsiveness to stimuli. The reversible and oriented immobilization and micropatterning of ferrocene-tagged yellow fluorescent proteins (Fc-YFPs) onto ß-cyclodextrin (ßCD) molecular printboards was characterized using surface plasmon resonance (SPR) spectroscopy and fluorescence microscopy in combination with electrochemistry. The proteins were assembled on the surface through the specific supramolecular host-guest interaction between ßCD and ferrocene. Application of a dynamic covalent disulfide lock between two YFP proteins resulted in a switch from monovalent to divalent ferrocene interactions with the ßCD surface, yielding a more stable protein immobilization. The SPR titration data for the protein immobilization were fitted to a 1:1 Langmuir-type model, yielding K(LM) = 2.5 × 10(5) M(-1) and K(i,s) = 1.2 × 10(3) M(-1), which compares favorably to the intrinsic binding constant presented in the literature for the monovalent interaction of ferrocene with ßCD self-assembled monolayers. In addition, the SPR binding experiments were qualitatively simulated, confirming the binding of Fc-YFP in both divalent and monovalent fashion to the ßCD monolayers. The Fc-YFPs could be patterned on ßCD surfaces in uniform monolayers, as revealed using fluorescence microscopy and atomic force microscopy measurements. Both fluorescence microscopy imaging and SPR measurements were carried out with the in situ capability to perform cyclic voltammetry and chronoamperometry. These studies emphasize the repetitive desorption and adsorption of the ferrocene-tagged proteins from the ßCD surface upon electrochemical oxidation and reduction, respectively.

The effectiveness of nurse-led care in general practice on clinical outcomes in adults with type 2 diabetes.

BACKGROUND: In Australia, diabetes was identified as a national health priority area in 1996; nevertheless the prevalence of type 2 diabetes has increased dramatically since then. Nurses have been working within Australian general practices for several decades but only in recent years has the role of the practice nurse in primary health care increased. OBJECTIVES: This review aims to identify the effectiveness of nurse-led care in general practice as compared to general practitioner care on clinical outcomes in adults with type 2 diabetes. INCLUSION CRITERIA: Participants were adults (aged >18 years), with diabetes type 2 attending a general/family practice.Interventions of interest include nurse-led care in general practice in which the nurse is identified as taking a lead role in the care of patients with type 2 diabetes compared to general practitioner-led care.To evaluate the effectiveness of nurse-led diabetes care in general practice, this review sought randomised controlled trials as the study design of choice. Other research designs such as controlled clinical trials, interrupted time series and controlled before and after designs were also considered.The outcomes of interest were clinical outcomes including changes in systolic and diastolic blood pressure, body mass index, cholesterol levels, HbA1c (glycated haemoglobin) and fasting blood glucose. SEARCH STRATEGY: A three step literature search was conducted for English language articles from January 1990 to December 2011. METHODOLOGICAL QUALITY: Quantitative papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument. DATA COLLECTION: Quantitative data was extracted from papers included in the review using the standardised data extraction tool from the Joanna Briggs Institute. The data extracted included specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. DATA SYNTHESIS: Data from quantitative papers, where possible, were pooled in statistical meta-analysis using the Meta-Analysis of Statistics Assessment and Review Instrument. Additionally, RevMan 5 was used for presenting forest plots of the meta-analysis. RESULTS: The electronic search yielded 804 potentially relevant papers of which 49 papers appeared to satisfy the criteria for inclusion and full texts of these papers were assessed against the inclusion criteria by two independent reviewers. From these papers, five were included in the review, four randomised control trials and one quasi-experimental study. These articles provided evidence that nurse-led care improves blood pressure and cholesterol levels for patients with type 2 diabetes attending a general practice. CONCLUSIONS: There is some evidence to support the use of nurse-led care in general practice for patients with type 2 diabetes. IMPLICATIONS FOR PRACTICE: If nurse-led care is implemented in the care of people with type 2 diabetes consideration needs to be given to the use of clinical algorithms, goal setting, individualised care plans, self management and follow up of lifestyle risk factors. IMPLICATION FOR RESEARCH: More randomised controlled trials are required to assess the efficacy of nurse-led care including cost effectiveness.

Cucurbit[8]uril induced heterodimerization of methylviologen and naphthalene functionalized proteins.

Cucurbit[8]uril is a supramolecular inducer of protein heterodimerization for proteins appended with methylviologen and naphthalene host elements. Two sets of fluorescent protein pairs, which visualize the specific protein assembly process, enabled the interplay of the supramolecular elements with the proteins to be established.

Functional implications of modifying RyR-activating peptides for membrane permeability.

1. Our aim was to determine whether lipoamino acid conjugation of peptides that are high-affinity activators of ryanodine receptor (RyR) channels would (a) render the peptides membrane permeable, (b) alter their structure or (a) reduce their activity. The peptides correspond to the A region of the II-III loop of the skeletal dihydropyridine receptor. 2. The lipoamino acid conjugation increased the apparent permeability of the peptide across the Caco-2 cell monolayer by up to approximately 20-fold. 3. Nuclear magnetic resonance showed that the alpha-helical structure of critical basic residues, required for optimal activation of RyRs, was retained after conjugation. 4. The conjugated peptides were more effective in enhancing resting Ca2+ release, Ca2+-induced Ca2+ release and caffeine-induced Ca2+ release from isolated sarcoplasmic reticulum (SR) than their unconjugated counterparts, and significantly enhanced caffeine-induced Ca2+ release from mechanically skinned extensor digitorum longus (EDL) fibres. 5. The effect of both conjugated and unconjugated peptides on Ca2+ release from skeletal SR was 30-fold greater than their effect on either cardiac Ca2+ release or on the Ca2+ Mg2+ ATPase. 6. A small and very low affinity effect of the peptide in slowing Ca2+ uptake by the Ca2+, Mg2+ ATPase was exacerbated by lipoamino acid conjugation in both isolated SR and in skinned EDL fibres. 7. The results show that lipoamino acid conjugation of A region peptides increases their membrane permeability without impairing their structure or efficacy in activating skeletal and cardiac RyRs.