Medicine (RMH) - Research Publications
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ItemNo Preview AvailableNo association between mannose-binding lectin deficiency and H1N1 2009 infection observed during the first season of this novel pandemic influenza virus(ELSEVIER SCIENCE INC, 2011-11)Genetic variations in host immunity may influence susceptibility to novel infections like the recently emergent pandemic influenza virus. Prior studies demonstrated that mannose-binding lectin (MBL) inactivates influenza. Furthermore, MBL deficiency is common and appears to predispose to respiratory virus infections. Therefore, we studied whether MBL deficiency played a role in infection with the novel H1N1 2009 influenza strain in exposed health care workers. In a nested case-control study, we observed no association between phenotypic MBL deficiency, variously defined, and predisposition to H1N1 2009 influenza in 63 pairs of seropositive and seronegative participants. MBL appears to currently have little impact on innate immune responses to H1N1 2009 influenza.
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ItemOseltamivir Resistance in Adult Oncology and Hematology Patients Infected with Pandemic (H1N1) 2009 Virus, Australia(CENTERS DISEASE CONTROL, 2010-07)We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after > or = 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.
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ItemFacilitating Surveillance of Pulmonary Invasive Mold Diseases in Patients with Haematological Malignancies by Screening Computed Tomography Reports Using Natural Language Processing(PUBLIC LIBRARY SCIENCE, 2014-09-24)PURPOSE: Prospective surveillance of invasive mold diseases (IMDs) in haematology patients should be standard of care but is hampered by the absence of a reliable laboratory prompt and the difficulty of manual surveillance. We used a high throughput technology, natural language processing (NLP), to develop a classifier based on machine learning techniques to screen computed tomography (CT) reports supportive for IMDs. PATIENTS AND METHODS: We conducted a retrospective case-control study of CT reports from the clinical encounter and up to 12-weeks after, from a random subset of 79 of 270 case patients with 33 probable/proven IMDs by international definitions, and 68 of 257 uninfected-control patients identified from 3 tertiary haematology centres. The classifier was trained and tested on a reference standard of 449 physician annotated reports including a development subset (n = 366), from a total of 1880 reports, using 10-fold cross validation, comparing binary and probabilistic predictions to the reference standard to generate sensitivity, specificity and area under the receiver-operating-curve (ROC). RESULTS: For the development subset, sensitivity/specificity was 91% (95%CI 86% to 94%)/79% (95%CI 71% to 84%) and ROC area was 0.92 (95%CI 89% to 94%). Of 25 (5.6%) missed notifications, only 4 (0.9%) reports were regarded as clinically significant. CONCLUSION: CT reports are a readily available and timely resource that may be exploited by NLP to facilitate continuous prospective IMD surveillance with translational benefits beyond surveillance alone.
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ItemAntimicrobial stewardship in residential aged care facilities: need and readiness assessment(BMC, 2014-07-23)BACKGROUND: Information about the feasibility, barriers and facilitators of antimicrobial stewardship (AMS) in residential aged care facilities (RACFs) has been scant. Exploring the prevailing perceptions and attitudes of key healthcare providers towards antibiotic prescribing behaviour, antibiotic resistance and AMS in the RACF setting is imperative to guide AMS interventions. METHODS: Semi-structured interviews and focus groups were conducted with key RACF healthcare providers until saturation of themes occurred. Participants were recruited using purposive and snowball sampling. The framework approach was applied for data analysis. RESULTS: A total of 40 nurses, 15 general practitioners (GPs) and 6 pharmacists from 12 RACFs were recruited. Five major themes emerged; perceptions of current antibiotic prescribing behaviour, perceptions of antibiotic resistance, attitude towards and understanding of AMS, perceived barriers to and facilitators of AMS implementation, and feasible AMS interventions. A higher proportion of GPs and pharmacists compared with nurses felt there was over-prescribing of antibiotics in the RACF setting. Antibiotic resistance was generally perceived as an issue for infection control rather than impacting clinical decisions. All key stakeholders were supportive of AMS implementation in RACFs; however, they recognized barriers related to workload and logistical issues. A range of practical AMS interventions were identified, with nursing-based education, aged-care specific antibiotic guidelines and regular antibiotic surveillance deemed most useful and feasible. CONCLUSIONS: Areas of antibiotic over-prescribing have been identified from different healthcare providers' perspectives. However, concern about the clinical impact of antibiotic resistance was generally lacking. Importantly, information gathered about feasibility, barriers and facilitators of various AMS interventions will provide important insights to guide development of AMS programs in the RACF setting.
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ItemLow T-Cell Responses to Mitogen Stimulation Predicts Poor Survival in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation(FRONTIERS MEDIA SA, 2017-11-09)BACKGROUND: Successful engraftment and reconstitution of the innate and adaptive immune system are associated with improved outcomes in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). A clinically meaningful and simple biomarker of immunosuppression could potentially assist clinicians in their decision-making. We aimed to determine the relationship between T-cell production of interferon gamma (IFN-γ) in response to phytohemagglutinin (PHA) to clinical outcomes in HSCT recipients. METHODS: A prospective observational multicenter study of 73 adult allogeneic HSCT recipients was conducted in Melbourne, Australia. Eligible participants were >18 years and at risk of cytomegalovirus disease. T-cell responses to PHA were assessed at 3, 6, 9, and 12 months post-HSCT using the commercial quantiferon-cytomegalovirus assay, which quantifies IFN-γ production by ELISA following stimulation with PHA. A low response was defined as IFN-γ <0.5 IU/ml following stimulation with PHA. RESULTS: At 3 months post-HSCT, high responses to PHA (median IFN-γ 7.68 IU/ml) were seen in 63% of participants and low responses to PHA (median IFN-γ 0.06 IU/ml) in 37%. IFN-γ responses to PHA were significantly associated with the severity of acute graft versus host disease (AGVHD) (spearman r = -0.53, p < 0.001) and correlated with blood lymphocyte count (spearman r = 0.52, p < 0.001). Twelve month overall survival was greater in individuals with high compared to low IFN-γ response to PHA at 3 months [92 vs. 62%, respectively, Cox proportional hazard ratio (HR): 4.12 95% CI: 1.2-13.7, p = 0.02]. Non-relapse mortality (NRM) was higher in individuals with low IFN-γ response to PHA (competing risk regression HR 11.6 p = 0.02). In individuals with no AGVHD compared to AGVHD and high IFN-γ response to PHA compared to AGVHD and low IFN-γ response to PHA, 12-month survival was 100 vs. 80 vs. 52%, respectively (log rank test p < 0.0001). CONCLUSION: Low IFN-γ response to PHA at the 3-month time-point following allogeneic HSCT was predictive of reduced 12-month overall survival, increased NRM, and reduced survival in recipients with AGVHD. Assessing IFN-γ response to PHA post-HSCT may be a clinically useful immune biomarker.
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ItemStaphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis(SPRINGER, 2013-08)Staphylococcus aureus bacteraemia (SAB) is an important cause of community and nosocomial sepsis, with a significant mortality rate. Infective endocarditis (IE) is a serious complication, occurring in up to 25 % of cases. Transoesophageal echocardiography (TOE) significantly improves the sensitivity of diagnosis. We compared the sensitivity and specificity of clinical evaluation alone in diagnosing IE. We evaluated all adult patients with SAB at our centre from 1998 to 2006 in order to determine what proportion of clinically unsuspected cases were diagnosed with IE on TOE. IE was defined according to modified Duke criteria. The median age of the patients was 68 years, 77 % were male and the majority of cases did not have a known pre-existing condition. Twenty-one percent were methicillin-resistant Staphylococcus aureus (MRSA). Intravascular device was the most common cause of bacteraemia. TOE was performed in 144 (100 %) of the cases. IE was suspected clinically in 15 % of cases, and the overall prevalence of possible or definite IE on TOE-inclusive Duke criteria was 29 % (n = 41). Following TOE, 22 (15 %) cases were reclassified as either possible or definite endocarditis. TOE detected a vegetation in 37 (90 %) of the 41 cases of IE. Nineteen (46 %) were not suspected clinically by Duke criteria. Sensitivity improved in the presence of pre-existing valve lesion or community acquisition. The overall in-hospital mortality was 10 %. There is a high incidence of endocarditis in SAB and a large percentage of cases are not evident on clinical grounds. TOE evaluation is indicated for all medically suitable adult patients with SAB in order to improve the detection of endocarditis.
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ItemPandemic (H1N1) 2009 Risk for Frontline Health Care Workers(CENTERS DISEASE CONTROL, 2011-06)To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls. Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84-2.22). Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results. Higher numbers of children in a participant's family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors. This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission.
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ItemAlcoholic Chlorhexidine or Alcoholic Iodine Skin Antisepsis (ACAISA): protocol for cluster randomised controlled trial of surgical skin preparation for the prevention of superficial wound complications in prosthetic hip and knee replacement surgery(BMJ PUBLISHING GROUP, 2014)INTRODUCTION: Wound complications following arthroplasty are associated with significant impact on the patient and healthcare system. Skin cleansing prior to surgical incision is a simple and effective method to prevent wound complications however, the question of which agent is superior for surgical skin antisepsis is unresolved. METHODS AND ANALYSIS: This cluster randomised controlled trial aims to compare the incidence of superficial wound complications in patients undergoing elective prosthetic hip or knee replacement surgery receiving surgical skin antisepsis with either: 0.5% chlorhexidine gluconate (CHG) in 70% alcohol or 10% povidone in 70% alcohol. The trial will be conducted at an Australian tertiary, university affiliated hospital over a 3-year period involving 750 participants. Participants will be drawn from the surgical waiting list. Consent for this study will be 'opt-out' consent. On a given day, all eligible participants will have skin preparation either with 0.5% chlorhexidine in 70% alcohol or 10% povidone iodine in 70% alcohol. The primary outcome is superficial wound complications (comprised of superficial incisional surgical site infections (SSI) and/or prolonged wound ooze) in the first 30 days following prosthetic joint replacement surgery. Secondary outcomes will include the incidence of wound complications according to the joint replaced, assessment of the causative agents of SSI and cost-effectiveness analysis. The primary analysis is an intention-to-treat analysis including all participants who undergo randomisation and will be performed at the individual level taking into account the clustering effect. ETHICS AND DISSEMINATION: The study design and protocol was reviewed and approved by the St Vincent's Hospital Human Research Ethics Committee (HREC-A 016/14 10/3/2014). Study findings will be disseminated in the printed media, and learned forums. A written lay summary will be available to study participants on request. TRIAL REGISTRATION NUMBER: The trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614000177651.