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    Quality of Life Impact of an Adjuvanted Recombinant Zoster Vaccine in Adults Aged 50 Years and Older
    Curran, D ; Oostvogels, L ; Heineman, T ; Matthews, S ; McElhaney, J ; McNeil, S ; Diez-Domingo, J ; Lal, H ; Andrews, C ; Athan, E ; Berglund, J ; Campora, L ; de Looze, F ; Korhonen, T ; Leung, E ; Levin, M ; Volpi, A ; Johnson, RW (OXFORD UNIV PRESS INC, 2019-08)
    BACKGROUND: To determine the efficacy of an adjuvanted recombinant zoster vaccine in reducing the herpes zoster (HZ) burden of illness, HZ burden of interference with activities of daily living, and HZ impact on quality of life. METHODS: The assessments were integrated in two Phase III trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229). HZ burden of illness and HZ burden of interference with activities of daily living were assessed by the Zoster Brief Pain Inventory (ZBPI) instrument and quality of life by the EuroQol-5 Dimension (EQ-5D) utility index and the SF-36 health survey. We report the ZOE-50 results and a pooled analysis of patients aged 70 years and older from the trials combined. RESULTS: The estimated vaccine efficacy in reducing HZ burden of illness and HZ burden of interference was greater than 90% in both the ZOE-50 and the pooled ZOE-70 analysis. In confirmed HZ cases, adjuvanted recombinant zoster vaccine reduced the maximal ZBPI worst-pain score in the pooled ZOE-70 analysis (p = .032) and the maximal ZBPI average-pain scores in both the ZOE-50 (p = .049) and the pooled ZOE-70 analysis (p = .043). In breakthrough HZ cases, trends for diminished loss of quality of life compared with placebo-recipient HZ cases were observed, with differences up to 0.14 on the EQ-5D index at time points during the 4 weeks following HZ onset. CONCLUSIONS: Adjuvanted recombinant zoster vaccine reduced the HZ burden of illness significantly, particularly due to its very high vaccine efficacy in preventing HZ. For breakthrough HZ cases, the results suggest that the adjuvanted recombinant zoster vaccine mitigated severity of HZ-related pain, burden of interference with activities of daily living, and recipients' utility loss.
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    Antibiotic complications during the treatment of Mycobacterium ulcerans disease in Australian patients
    O'Brien, DP ; Friedman, D ; Hughes, A ; Walton, A ; Athan, E (WILEY, 2017-09)
    BACKGROUND: Antibiotics are the recommended first-line treatment for Mycobacterium ulcerans disease. Antibiotic toxicity is common in Australian patients, yet antibiotic complication rates and their risk factors have not been determined. AIM: To determine the incidence rate and risk factors for antibiotic toxicity in Australian patients treated for M. ulcerans disease. METHODS: An analysis of severe antibiotic complications was performed using data from a prospective cohort of M. ulcerans cases managed at Barwon Health from 1 January 1998 to 30 June 2016. A severe antibiotic complication was defined as an antibiotic adverse event that required its cessation. Antibiotic complication rates and their associations were assessed using a Poisson regression model. RESULTS: A total of 337 patients was included; 184 (54.6%) males and median age 57 years (interquartile range (IQR) 36-73 years). Median antibiotic treatment duration was 56 days (IQR 49-76 days). Seventy-five (22.2%) patients experienced severe antibiotic complications after a median 28 days (IQR 17-45 days) at a rate of 141.53 per 100 person-years (95% confidence interval (CI) 112.86-177.47). Eleven (14.7%) patients required hospitalisation. Compared with rifampicin/clarithromycin combinations, severe complication rates were not increased for rifampicin/ciprofloxacin (rate ratio (RR) 1.49, 95% CI 0.89-2.50, P = 0.13) or rifampicin/moxifloxacin (RR 2.54, 95% CI 0.76-8.50, P = 0.13) combinations, but were significantly increased for 'other' combinations (RR 2.53, 95% CI 1.13-5.68, P = 0.03). In a multivariable analysis, severe complication rates were significantly increased with reduced estimated glomerular filtration rates (EGFR) (adjusted rate ratio (aRR) 2.65, 95% CI 1.24-5.65 for EGFR 60-89 mL/min and aRR 1.31, 95% CI 0.49-3.53 for EGFR 0-59 mL/min compared with EGFR ≥90 mL/min, P < 0.01) and female gender (aRR 2.15, 95% CI 1.38-3.30, P < 0.01). CONCLUSIONS: Severe antibiotic complications during M. ulcerans treatment are high with increased rates independently associated with reduced renal function and female gender.
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    Identifying and integrating patient and caregiver perspectives for clinical practice guidelines on the screening and management of infectious microorganisms in hemodialysis units
    Miller, HM ; Tong, A ; Tunnicliffe, DJ ; Campbell, D ; Pinter, J ; Commons, RJ ; Athan, E ; Craig, JC ; Gilroy, N ; Green, J ; Henderson, B ; Howell, M ; Stuart, RL ; van Eps, C ; Wong, MG ; de Zoysa, J ; Jardine, MJ (WILEY, 2017-04)
    INTRODUCTION: The integration of patient and caregiver input into guideline development can help to ensure that clinical care addresses patient expectations, priorities, and needs. We aimed to identify topics and outcomes salient to patients and caregivers for inclusion in the Kidney Health Australia Caring for Australasians with Renal Impairment (KHA-CARI) clinical practice guideline on the screening and management of infectious microorganisms in hemodialysis units. METHODS: A facilitated workshop was conducted with 11 participants (patients [n = 8], caregivers [n = 3]). Participants identified and discussed potential topics for inclusion in the guidelines, which were compared to those developed by the guideline working group. The workshop transcript was thematically analyzed to identify and describe the reasons underpinning their priorities. FINDINGS: Patients and caregivers identified a range of topics already covered by the scope of the proposed guidelines and also suggested additional topics: privacy and confidentiality, psychosocial care during/after disease notification, quality of transportation, psychosocial treatment of patients in isolation, patient/caregiver education and engagement, and patient advocacy. Five themes characterized discussion and underpinned their choices: shock and vulnerability, burden of isolation, fear of infection, respect for privacy and confidentiality, and confusion over procedural inconsistencies. DISCUSSION: Patients and caregivers emphasized the need for guidelines to address patient education and engagement, and the psychosocial implications of communication and provision of care in the context of infectious microorganisms in hemodialysis units. Integrating patient and caregiver perspectives can help to improve the relevance of guidelines to enhance quality of care, patient experiences, and health and psychosocial outcomes.
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    Silent but deadly: patients with enterococcal bacteraemia should be assessed for colorectal neoplasia
    Athan, E ; Cabiltes, I ; Coghill, S ; Bowe, SJ (WILEY, 2019-02-04)
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    Fosfomycin: what was old is new again
    Avent, ML ; Rogers, BA ; Cheng, AC ; Athan, E ; Francis, JR ; Roberts, MJ ; Paterson, DL ; Harris, PNA (WILEY, 2018-12)
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    Australian infection control in endoscopy consensus statements on carbapenemase-producing Enterobacteriaceae
    Devereaux, BM ; Athan, E ; Brown, RR ; Greig, SM ; Jones, DM ; Bailey, FK ; Wallis, DJ ; Singh, R (WILEY, 2019-04)
    Outbreaks of carbapenemase-producing Enterobacteriaceae clinical infections related to endoscopic transmission are well documented. The high morbidity and mortality associated with these infections emphasizes the need to reassess endoscopic reprocessing protocols. The Gastroenterological Society of Australia established a multi-society committee to formulate evidence-based consensus statements on the prevention and management of endoscopic transmission of carbapenemase-producing Enterobacteriaceae. A literature search was undertaken utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Nine statements were formulated. Using the Delphi methodology, the statements were initially reviewed electronically by the committee members and subsequently at a face-to-face meeting in Melbourne, Australia. After further discussion, four additional sub-statements were added resulting in a total of 13 statements. Each statement was assessed for level of evidence, recommendation grade and the voting on recommendation was recorded. For a statement to be accepted, five out of six committee members had to "accept completely" or "accept with some reservation." All 13 statements achieved consensus agreement. Eleven statements achieved 100% "accepted completely." Two statements were 83% "accepted completely" and 17% "accepted with some reservation." Of particular significance, automated flexible endoscope reprocessors were mandated for high-level disinfection, and the use of forced-air drying cabinets was mandated for endoscope storage. These evidence-based statements encourage preventative strategies with the aim of ensuring the highest possible standards in flexible endoscope reprocessing thereby optimizing patient safety. They must be considered in addition to the broader published guidelines on infection control in endoscopy.
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    Mycobacterium ulcerans disease management in Australian patients: the re-emergence of surgery as an important treatment modality
    O'Brien, DP ; Callan, P ; Friedman, ND ; Athan, E ; Hughes, A ; McDonald, A (WILEY, 2019-06)
    With the demonstration of the effectiveness of antibiotic treatment, the management of Mycobacterium ulcerans disease has changed from a predominantly surgically to a predominantly medically treated disease. However, research among Australian patients has revealed that antibiotic treatment alone is associated with prolonged wound healing times, high rates of treatment toxicity, and the potential for significant tissue destruction associated with severe paradoxical reactions. We present the current state of M. ulcerans management in Barwon Health, Australia, where a close working relationship exists between the Plastic Surgical and Infectious Diseases units. Here treatment has evolved based on nearly 20 years of experience gained from managing more around 600 patients from a M. ulcerans epidemic on the nearby Bellarine and Mornington Peninsulas. In our experience, surgery has re-emerged to play an important role in the treatment of M. ulcerans in improving the rate of wound healing, minimizing antibiotic associated toxicity and preventing further tissue loss associated with severe paradoxical reactions. For selected small lesions surgery without antibiotics may also be an effective treatment option, however aggressive surgical resection of lesions with wide margins through uninvolved tissue should no longer be performed. Furthermore, extensive excisional surgery that will require the use of split skin grafts and vascularized tissue flaps to repair skin defects should be avoided if possible.
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    Aiming for elimination: Outcomes of a consultation pathway supporting regional general practitioners to prescribe direct-acting antiviral therapy for hepatitis C.
    Wade, AJ ; McCormack, A ; Roder, C ; McDonald, K ; Davies, M ; Scott, N ; Wardrop, M ; Athan, E ; Hellard, ME (Wiley, 2018-09)
    To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV)-in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule prescription data were used to evaluate GP DAA prescription 12 months pre-and post- pathway implementation. A retrospective review of patients referred for remote consultation for 12 months post- pathway inception was undertaken to determine the care cascade. HCV treatment initiation by GPs increased after implementation of the remote consultation pathway. In the 12-month study period, 74 GPs referred 169 people for remote consultation; 114 (67%) were approved for GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119 (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post-treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15 achieved SVR ranging from week 5 to 11 post-treatment. No treatment failure was detected. Collaborative development and implementation of a remote consultation pathway has engaged regional GPs in managing HCV. Follow-up post-treatment could be improved; however, no treatment failure has been documented. To eliminate HCV as a public health threat, it is vital that specialists support GPs to prescribe DAA.
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    Increased Severity and Spread of Mycobacterium ulcerans, Southeastern Australia
    Tai, AYC ; Athan, E ; Friedman, ND ; Hughes, A ; Walton, A ; O'Brien, DP (CENTERS DISEASE CONTROL & PREVENTION, 2018-01)
    Reported cases of Mycobacterium ulcerans disease (Buruli ulcer) have been increasing in southeastern Australia and spreading into new geographic areas. We analyzed 426 cases of M. ulcerans disease during January 1998-May 2017 in the established disease-endemic region of the Bellarine Peninsula and the emerging endemic region of the Mornington Peninsula. A total of 20.4% of cases-patients had severe disease. Over time, there has been an increase in the number of cases managed per year and the proportion associated with severe disease. Risk factors associated with severe disease included age, time period (range of years of diagnosis), and location of lesions over a joint. We highlight the changing epidemiology and pathogenicity of M. ulcerans disease in Australia. Further research, including genomic studies of emergent strains with increased pathogenicity, are urgently needed to improve the understanding of disease to facilitate implementation of effective public health measures to halt its spread.
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    Exposure Risk for Infection and Lack of Human-to-Human Transmission of Mycobacterium ulcerans Disease, Australia
    O'Brien, DP ; Wynne, JW ; Buultjens, AH ; Michalski, WP ; Stinear, TR ; Friedman, ND ; Hughes, A ; Athan, E (CENTERS DISEASE CONTROL, 2017-05)
    We conducted epidemiologic and genetic analyses of family clusters of Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found that the incidence of M. ulcerans disease in family members was increased. However, the risk for exposure appeared short-term and not related to human-human transmission.