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Hawkes E.A.,Austin Hospital | Hawkes E.A.,Eastern Health | Hawkes E.A.,Monash University | Grigg A.,Austin Hospital | And 4 more authors.
The Lancet Oncology | Year: 2015

Cancers can evade the host immune system by inducing upregulation of immune inhibitory signals. Anti-programmed cell death-1 (PD-1) monoclonal antibodies block these inhibitory signals allowing the host to mount an immune response against malignant cells. This class of drugs is active in solid tumours, where upregulation of cell-surface PD-1 ligand proteins is nearly uniform. Because lymphoma is a malignancy of immune system cells, the role of the PD-1 pathway in these neoplasms is more complex. However, early clinical trials using PD-1 inhibitors have shown significant clinical activity in various subtypes of relapsed lymphoma. In this Review, we assess the scientific literature on the role of the PD-1 pathway in lymphoma, the relevant clinical data for PD-1 inhibition, and future strategies for this next generation of anticancer agents. © 2015 Elsevier Ltd.

Atan R.,Monash University | Crosbie D.C.A.,Northern Hospital | Bellomo R.,Monash University
Renal Failure | Year: 2013

Background and aims: Hypercytokinemia is believed to be harmful and reducing cytokine levels is considered beneficial. Extracorporeal blood purification (EBP) techniques have been studied for the purpose of cytokine reduction. We aimed to study the efficacy of various EBP techniques for cytokine removal as defined by technical measures. Method: We conducted a systematic search for human clinical trials which focused on technical measures of cytokine removal by EBP techniques. We identified 41 articles and analyzed cytokine removal according to clearance (CL), sieving coefficient (SC), ultrafiltrate (UF) concentration and percentage removed. Results: We identified the following techniques for cytokine removal: standard hemofiltration, high volume hemofiltration (HVHF), high cut-off (HCO) hemofiltration, plasma filtration techniques, and adsorption techniques, ultrafiltration (UF) techniques relating to cardiopulmonary bypass (CPB), extracorporeal liver support systems and hybrid techniques including combined plasma filtration adsorption. Standard filtration techniques and UF techniques during CPB were generally poor at removing cytokines (median CL for interleukin 6 [IL-6]: 1.09 mL/min, TNF-alpha 0.74 mL/min). High cut-off techniques consistently offered moderate cytokine removal (median CL for IL-6: 26.5 mL/min, interleukin 1 receptor antagonist [IL-1RA]: 40.2 mL/min). Plasma filtration and extracorporeal liver support appear promising but data are few. Only one paper studied combined plasma filtration and adsorption and found low rates of removal. The clinical significance of the cytokine removal achieved with more efficacious techniques is unknown. Conclusion: Human clinical trials indicate that high cut-off hemofiltration techniques, and perhaps plasma filtration and extracorporeal liver support techniques are likely more efficient in removing cytokines than standard techniques. © 2013 Informa Healthcare USA, Inc. All rights reserved.

Shepherd S.J.,La Trobe University | Halmos E.,Shepherd Works P L | Glance S.,Northern Hospital
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014

Purpose of review: Irritable bowel syndrome (IBS) is a condition affecting approximately 10-15% of Western populations. The Rome III criteria are applied to many studies to validate the diagnosis of IBS. The low fermentable oligo, di, monosaccharides and polyol (FODMAP) diet has been the subject of many robust clinical trials and is now used as the primary dietary therapy internationally. This review examines the current evidence for the role of the low FODMAP diet in IBS. Recent findings: Detailed commentary on original research involving FODMAPs and IBS symptoms from 2013 to 2014 is provided. Summary: The low FODMAP diet has been shown to be an efficacious therapy for reduction of functional gastrointestinal symptoms seen in IBS. Recent publications provide randomized controlled trial and prospective observational evidence in support of the diet for symptom management. The low FODMAP diet appears to be superior to a gluten-free diet in people with self-reported nonceliac gluten sensitivity. Although the low FODMAP diet has not been shown to reduce the prebiotic effect in the colon, total colonic bacterial load was reduced. Further research investigating the potential health implications of both this and the nutritional adequacy of the liberalized low FODMAP diet is required. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Ariathianto Y.,Northern Hospital
Australian Family Physician | Year: 2011

Aim: To identify the prevalence of asymptomatic bacteriuria in the elderly population and to examine associated risk factors, complications and natural history, and whether treatment improves prognosis. Methods: A literature search of MEDLINE, PubMed and the Cochrane Library was undertaken of studies published from 1980 to 2009. A total of 70 articles were identified. Emphasis was given to randomised controlled trials, review articles and more recent publications. Results: Asymptomatic bacteriuria is common in the elderly, especially among institutionalised or hospitalised patients. Risk factors include cognitive impairment, diabetes mellitus, structural urinary tract abnormalities and indwelling catheters. Antimicrobial therapy does not result in improved survival or genitourinary morbidity and may potentially cause avoidable side effects and the emergence of resistant organisms. Conclusion: Bacteriuria is common in functionally impaired elderly patients. In the absence of symptoms or signs of infection, routine dipstick screening and subsequent antimicrobial therapy is not recommended.

Berlowitz D.J.,Northern Hospital | Graco M.,University of Melbourne
Australian Health Review | Year: 2010

Background. The Northern Alliance Hospital Admission Risk ProgramChronic Disease Management comprises 13 services delivering care to those with chronic disease and older people with complex care needs, who are frequent hospital users. Aims. To develop and implement a system-wide approach to the evaluation of this existing program. Methods. The Northern Clinical Research Centre audited all existing, routinely collected administrative data within the program and then met with each service to develop service specific outcome measures. The evaluators then developed and implemented a system-wide evaluation approach to measure performance in terms of: client profile; access and entry; service efficiency; client outcomes; and hospital demand. Results. Data are collected electronically and more than 80% are derived from existing, administrative datasets, minimising staff and client burden. Additional data include client outcomes and a health related quality of life measure. The preliminary twelve month data suggest that clients have the equivalent of 'fair' or 'poor' self-reported health status (n≤862) and the average health utility scores are significantly (P0.05) worse than population control data. These analyses reveal, for the first time, that the Northern Alliance Hospital Admission Risk ProgramChronic Disease Management program is targeting appropriate clients. Discussion. This methodology will enable many prospective assessments to be performed including; client outcome evaluation, service model comparisons, and cost-utility analyses. Conclusion. This evaluation approach demonstrates the feasibility of a highly coordinated 'whole of system' evaluation. Such an approach may ultimately contribute to the development of evidence-based policy. What is known about the topic? Program evaluation literature recommends establishing the objectives of a program, and the corresponding evaluation methodology early in the planning phase so that a thorough evaluation can commence with the implementation of the program. What does this paper add? This paper provides an alternative evaluation methodology developed around the available administrative data, thereby maximising efficiency with data collection and analysis with minimal burden on clinicians. This pragmatic approach may be appropriate for large, ongoing programs with an existing administrative dataset and where funding for evaluation is limited. What are the implications for practitioners? This paper has implications for both administrators and clinicians. The methodology is designed to facilitate evidence-based policy and planning at a regional and state level, and to assist with quality improvement at the local service level through ongoing performance monitoring and benchmarking. © AHHA 2010.

Considine J.,Deakin University | Lucas E.,Deakin University | Lucas E.,Northern Hospital | Wunderlich B.,Northern Hospital
Critical Care and Resuscitation | Year: 2012

Objectives: To evaluate the uptake of an emergency department early warning system (ED EWS) for recognition of, and response to, clinical deterioration. Design, setting and participants: A descriptive exploratory study conducted in an urban district hospital in Melbourne, Australia. Systematic sampling was used to identify every 10th patient for whom the ED EWS was activated from May 2009 to May 2011. Main outcome measures: Patient characteristics, ED system data and ED EWS activation characteristics. Results: ED EWS activation occurred in 1.5% of ED patients; 204 patients were included in this pilot study. The median age was 65.1 years (interquartile range [IQR], 47.8-77.5 years), 89.2% of patients were classified as triage category 2 or 3, and 82.4% of patients were seen by medical staff before ED EWS activation. Hypotension (27.7%) and tachycardia (23.7%) were the most common reasons for ED EWS activation. Median duration of clinical instability was 39 minutes (IQR, 5- 129 minutes). Nurses made 93.1% of ED EWS activations. Median time between documenting physiological abnormalities and ED EWS activation was 5 minutes (IQR, 0- 20). Most patients (57.8%) required hospital admission: 4.4% of patients required intensive care unit admission. Conclusions: The ED EWS resulted in at least two formal reports of clinical deterioration in ED patients per day, indicating reasonable uptake by clinicians. A greater understanding of clinical deterioration in ED patients is warranted to inform an evidence-based approach to recognition of, and response to, clinical deterioration in ED patients.

The American Association for the Study of Liver Diseases just confirmed a grade I recommendation for hepatocellular carcinoma (HCC) screening despite growing controversy. Why should HCC be an exception in the long list of other cancers where the feasibility and the efficacy of screening were investigated by randomized trials? Only 12.0% of United States patients are screened, a fact that precludes efficacy, and there are no relevant figures on the benefit-risk ratio. The ethics of belief is a treacherous reef. Screening is not just performing a test, but is a public health issue: a national program is needed to ensure minimal participation, quality controls and evaluation of the results to improve the process. There are also serious concerns regarding undisclosed potential conflicts of interest. © 2013 Baishideng. All rights reserved.

Ho P.,Northern Hospital | Brooy B.L.,Northern Hospital | Hayes L.,Northern Hospital | Lim W.K.,Northern Hospital
Seminars in Thrombosis and Hemostasis | Year: 2015

Direct oral anticoagulants (DOACs) have changed the paradigm of anticoagulation management, improving patient convenience as well as possibly reducing the incidence of spontaneous intracranial hemorrhage. However, concerns remain with these agents because of the lack of monitoring capacity and availability of readily accessible specific antidotes. This is particularly pertinent in the older population, specifically the frail older adults who have multiple comorbidities, higher risk of falls, and increased bleeding risk. This group has not been specifically studied in the DOAC randomized controlled trials and, hence, extrapolation of these data into this population should be done cautiously. We provide a review of the use of DOACs in the older frail population from both hematological and geriatric perspectives, as well as propose an algorithm for how these agents may be used in this frail population.

Hang J.R.,Northern Hospital | Hutchinson A.F.,Northern Hospital | Hau R.C.,Northern Hospital
Journal of Pediatric Orthopaedics | Year: 2011

BACKGROUND: Closed reductions of distal radial fractures are among the most common orthopaedic operations but up to 39% of fractures lose position postoperatively. This study was carried out to determine the most significant risk factors for loss of position so that high-risk patients can be identified early and their management tailored accordingly. METHODS: We retrospectively reviewed 48 consecutive children who had redisplacement of their distal radial fractures after closed reduction and compared them with 48 matched controls. Fourteen risk factors were studied and analyzed with univariate and multivariate logistic regression analysis and receiver operating characteristics analysis. These risk factors included pre-reduction and post-reduction fracture characteristics as well as 4 previously described radiological indices of plaster quality. RESULTS: Significant independent clinical risk factors identified were the initial radial fracture displacement [odds ratio (OR) 1.03, P=0.001] and obliquity (OR 0.93, P=0.006), a completely displaced radial fracture (OR 5.21, P=0.003), an ipsilateral ulnar fracture (OR 3.56, P=0.003), residual radial displacement (OR 1.06, P=0.009), angulation (OR 1.16, P=0.011), and failure to achieve anatomical reduction (OR 0.18, P=0.004). Significant radiological indices included the Padding index (OR >100, P=0.004), Canterbury index (OR 99, P=0.014), and 3-point index (OR 19.29, P<0.001). Nonsignificant risk factors included the angulation of the initial radial fracture, a completely displaced ulnar fracture, plaster changes/splitting and the Cast index. The combined preoperative presence of a completely displaced radial fracture, an ipsilateral ulnar fracture and failure to achieve perfect reduction was found to be the best predictor of redisplacement (receiver operating characteristic area under the curve=0.82). This combination was found to be a better predictor of redisplacement than any of the radiological indices (receiver operating characteristic area under the curve ≤0.74) and it is also a more practical risk factor for the operating surgeon to use. CONCLUSIONS: The combination of a completely displaced distal radial fracture and an ipsilateral ulnar fracture, which then cannot be perfectly reduced, was the best predictor for redisplacement. We recommend that serious consideration be given to primary wire fixation in these patients. LEVEL OF EVIDENCE: III, prognostic. © 2011 Lippincott Williams & Wilkins, Inc.

Fu C.,Northeastern University China | Chen J.-J.,Northeastern University China | Zou H.,Northeastern University China | Meng W.-H.,Northern Hospital | And 2 more authors.
Optics Express | Year: 2012

Chaos-based image cipher has been widely investigated over the last decade or so to meet the increasing demand for real-time secure image transmission over public networks. In this paper, an improved diffusion strategy is proposed to promote the efficiency of the most widely investigated permutation-diffusion type image cipher. By using the novel bidirectional diffusion strategy, the spreading process is significantly accelerated and hence the same level of security can be achieved with fewer overall encryption rounds. Moreover, to further enhance the security of the cryptosystem, a plain-text related chaotic orbit turbulence mechanism is introduced in diffusion procedure by perturbing the control parameter of the employed chaotic system according to the cipher-pixel. Extensive cryptanalysis has been performed on the proposed scheme using differential analysis, key space analysis, various statistical analyses and key sensitivity analysis. Results of our analyses indicate that the new scheme has a satisfactory security level with a low computational complexity, which renders it a good candidate for real-time secure image transmission applications. © 2012 Optical Society of America.

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