Medicine (Western Health) - Research Publications
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ItemComparison of incidence, rate and length of all-cause hospital admissions between adults with normoglycaemia, impaired fasting glucose and diabetes: a retrospective cohort study in Geelong, Australia(BMJ PUBLISHING GROUP, 2018-03)OBJECTIVE: To determine whether adults with normoglycaemia, impaired fasting glucose (IFG) and diabetes differed according to the incidence, rate, length and primary reasons for hospital admission. DESIGN: Retrospective cohort study. SETTING: Barwon Statistical Division, Geelong, Australia. PARTICIPANTS: Cohort included 971 men and 924 women, aged 20+ years, participating in the Geelong Osteoporosis Study. Glycaemic status was assessed at cohort entry using fasting plasma glucose, use of antihyperglycaemic medication and/or self-report. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was any admission to the major tertiary public hospital in the study region over the follow-up period. Secondary outcome measures were admission rate and length (days). RESULTS: Over a median follow-up of 7.4 years (IQR 5.3-9.6), participants with diabetes, compared with those with normoglycaemia, were two times as likely to be hospitalised (OR 2.07, 95% CI 1.42 to 3.02), had a higher admission rate (incidence rate ratio 1.61, 95% CI 1.17 to 2.23) and longer hospital stay (third quartile difference 7.7, 95% CI 1.3 to 14.1 and ninth decile difference 16.2, 95% CI 4.2 to 28.3). IFG group was similar to normoglycaemia for the incidence, rate and length of admission. Cardiovascular disease-related diagnoses were the most common primary reasons for hospitalisation across all glycaemic categories. CONCLUSIONS: Our results show increased incidence, rate and length of all-cause hospital admission in adults with diabetes as compared with normoglycaemia; however, we did not detect any associations for IFG. Interventions should focus on preventing IFG-to-diabetes progression and reducing cardiovascular risk in IFG and diabetes.
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ItemImproving Delivery of Secondary Prophylaxis for Rheumatic Heart Disease in a High-Burden Setting: Outcome of a Stepped-Wedge, Community, Randomized Trial.(Ovid Technologies (Wolters Kluwer Health), 2018-07-17)BACKGROUND: Health system strengthening is needed to improve delivery of secondary prophylaxis against rheumatic heart disease. METHODS AND RESULTS: We undertook a stepped-wedge, randomized trial in northern Australia. Five pairs of Indigenous community clinics entered the study at 3-month steps. Study phases comprised a 12 month baseline phase, 3 month transition phase, 12 month intensive phase and a 3- to 12-month maintenance phase. Clinics received a multicomponent intervention supporting activities to improve penicillin delivery, aligned with the chronic care model, with continuous quality-improvement feedback on adherence. The primary outcome was the proportion receiving ≥80% of scheduled penicillin injections. Secondary outcomes included "days at risk" of acute rheumatic fever recurrence related to late penicillin and acute rheumatic fever recurrence rates. Overall, 304 patients requiring prophylaxis were eligible. The proportion receiving ≥80% of scheduled injections during baseline was 141 of 304 (46%)-higher than anticipated. No effect attributable to the study was evident: in the intensive phase, 126 of 304 (41%) received ≥80% of scheduled injections (odds ratio compared with baseline: 0.78; 95% confidence interval, 0.54-1.11). There was modest improvement in the maintenance phase among high-adhering patients (43% received ≥90% of injections versus 30% [baseline] and 28% [intensive], P<0.001). Also, the proportion of days at risk in the whole cohort decreased in the maintenance phase (0.28 versus 0.32 [baseline] and 0.34 [intensive], P=0.001). Acute rheumatic fever recurrence rates did not differ between study sites during the intensive phase and the whole jurisdiction (3.0 versus 3.5 recurrences per 100 patient-years, P=0.65). CONCLUSIONS: This strategy did not improve adherence to rheumatic heart disease secondary prophylaxis within the study time frame. Longer term primary care strengthening strategies are needed. CLINICAL TRIAL REGISTRATION: URL: www.anzctr.org.au. Unique identifier: ACTRN12613000223730.
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ItemQualitative Evaluation of a Complex Intervention to Improve Rheumatic Heart Disease Secondary Prophylaxis.(Ovid Technologies (Wolters Kluwer Health), 2018-07-17)BACKGROUND: Rheumatic heart disease is a high-burden condition in Australian Aboriginal communities. We evaluated a stepped-wedge, community, randomized trial at 10 Aboriginal communities from 2013 to 2015. A multifaceted intervention was implemented using quality improvement and chronic care model approaches to improve delivery of penicillin prophylaxis for rheumatic heart disease. The trial did not improve penicillin adherence. This mixed-methods evaluation, designed a priori, aimed to determine the association between methodological approaches and outcomes. METHODS AND RESULTS: An evaluation framework was developed to measure the success of project implementation and of the underlying program theory. The program theory posited that penicillin delivery would be improved through activities implemented at clinics that addressed elements of the chronic care model. Qualitative data were derived from interviews with health-center staff, informants, and clients; participant observation; and project officer reports. Quantitative data comprised numbers and types of "action items," which were developed by participating clinic staff with project officers to improve delivery of penicillin injections. Interview data from 121 health-center staff, 22 informants, and 72 clients revealed barriers to achieving the trial's aims, including project-level factors (short trial duration), implementation factors (types of activities implemented), and contextual factors (high staff turnover and the complex sociocultural environment). Insufficient actions were implemented addressing "self-management support" and "community linkage" streams of the chronic care model. Increased momentum was evident in later stages of the study. CONCLUSIONS: The program theory underpinning the study was sound. The limited impact made by the study on adherence was attributable to complex implementation challenges.
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ItemRecommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.(Wiley, 2018-09)STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, five guideline development groups (GDGs), and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (a) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (b) reducing unnecessary testing; (c) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (d) emphasizing evidence based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.
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ItemEffect of androgen deprivation therapy on the contractile properties of type I and type II skeletal muscle fibres in men with non-metastatic prostate cancer(WILEY, 2018-02)The contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and in age- and activity-matched healthy male subjects (Control). Mechanically-skinned muscle fibres were exposed to a sequence of heavily Ca2+ -buffered solutions at progressively higher free [Ca2+ ] to determine their force-Ca2+ relationship. Ca2+ -sensitivity was decreased in both type I and type II muscle fibres of ADT subjects relative to Controls (by -0.05 and -0.04 pCa units, respectively, P < .02), and specific force was around 13% lower in type I fibres of ADT subjects than in Controls (P = .02), whereas there was no significant difference in type II fibres. Treatment with the reducing agent dithiothreitol slightly increased specific force in type I and type II fibres of ADT subjects (by ~2%-3%, P < .05) but not in Controls. Pure type IIx fibres were found frequently in muscle from ADT subjects but not in Controls, and the overall percentage of myosin heavy chain IIx in muscle samples was 2.5 times higher in ADT subjects (P < .01). The findings suggest that testosterone suppression can negatively impact the contractile properties by (i) reducing Ca2+ -sensitivity in both type I and type II fibres and (ii) reducing maximum specific force in type I fibres.
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ItemPrecision oncology using a clinician-directed, tailored approach to molecular profiling(WILEY, 2018-02)AIM: Precision oncology involves molecularly matching patients to targeted agents usually in early drug development (EDD) programs. Molecular profiling (MP) identifies actionable targets. Comprehensive commercial MP platforms are costly and in resource limited environments, a more practical approach to MP is necessary to support EDD and precision oncology. We adopted a clinician-directed, tailored approach to MP to enrol patients onto molecularly targeted trials. We report the feasibility of this approach. METHODS: All patients referred to the Royal Melbourne Hospital (RMH) EDD between September 2013 and September 2015 were identified in a prospective database. Key captured data included clinicopathological data, MP platform ordered (if any), molecular targets identified and subsequent enrolment onto clinical trials. EDD-clinician decisions to order MP and the platform utilized was guided by patient consultation, tumor type, trial availability and requirement for molecular information. RESULTS: We identified 377 patients referred to RMH EDD. A total of 216 (57%) had MP ordered. The remainder had known actionable targets (19%), or were inappropriate for clinical trials (24%). In those undergoing MP, 187 genetic aberrations were found in 113 patients with 98 considered actionable targets in 86 patients. Ninety-eight (25%) patients were enrolled onto a clinical trial, including 40 (11%) receiving molecularly matched treatments. Median progression-free survival was improved in patients enrolled onto molecularly matched trials compared to those on unmatched trials (3.6 months vs 1.9 months, HR 0.58 [0.38-0.89], P = 0.013). CONCLUSION: A clinician-directed, tailored approach to the use of MP is feasible, resulting in 11% of patients enrolled onto molecularly matched trials.
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ItemPretreatment with dual antiplatelet therapy in patients with ST-elevation myocardial infarction(WILEY, 2018-08-01)BACKGROUND: The optimal time to administer P2Y12 inhibitors in patients with ST-elevation myocardial infarction (STEMI) remains to be defined. We sought to assess whether a pretreatment strategy was associated with improved coronary reperfusion and clinical outcomes. METHODS: Consecutive patients from the Melbourne Interventional Group registry (2005-2014) who presented with STEMI and underwent primary PCI were included. Those who received any P2Y12 inhibitor prior to arrival in the cardiac catheterisation laboratory were included in the pretreatment group. The primary endpoints were the proportion of patients with initial TIMI flow grade <3 and in-hospital bleeding. The secondary endpoints were 12-month mortality and major adverse cardiovascular events (MACE). RESULTS: Of the 2,807 patients included, 892(31.8%) received pretreatment. Clopidogrel was the most common P2Y12 inhibitor used (79.6%). Pretreatment was associated with less thromboaspiration and GPIIb/IIIa inhibitor use (both P < 0.01). Pretreatment was not associated with lower rates of TIMI flow <3 on initial angiogram (78.0% vs. 80.7%, P = 0.18) nor with increased in-hospital bleeding (3.6% vs. 3.9%, P = 0.67). Pretreatment was associated with lower 12-month mortality (4.7% vs. 7.0%, P = 0.02) but similar MACE rate (13.0% vs. 14.1%, P = 0.43). Multivariate analysis revealed pretreatment was not an independent predictor of 12-month mortality (OR 0.79; 95% CI 0.5-1.3, P = 0.32). CONCLUSION: Pretreatment with a P2Y12 inhibitor in patients with STEMI was not routine practice in our Australian cohort and was not associated with improved coronary reperfusion or clinical outcomes. Larger studies are required to definitively ascertain the risk/benefit ratio of dual antiplatelet therapy pretreatment in STEMI.
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ItemDo instability markers predict satisfactory reduction and requirement for later surgery in emergency department patients with wrist fracture?(WILEY, 2018-02)OBJECTIVE: Research suggests that the presence of instability markers in patients with displaced distal radial fractures is associated with poorer outcome. Our aims were to determine whether the presence of previously defined instability markers could predict the likelihood of successful ED reduction and requirement for a secondary procedure after ED reduction. METHODS: Retrospective cohort study performed by medical record review. Adult ED patients coded as having an isolated wrist fracture and having fracture reduction in ED were eligible for inclusion. Data collected included demographics, history of osteoporosis, mechanism of injury, radiological features on X-rays and performance of a secondary procedure. Outcomes of interest were the rate of successful fracture reduction in ED (against defined radiological criteria), the rate of secondary procedures and the association between the number of defined instability risk factors and successful reduction and performance of a secondary surgical procedure. Analysis was by χ2 test, receiver operating characteristic curve, logistic regression analyses. RESULTS: Three hundred and nineteen patients were studied; median age 62 years, 77% female. Sixty-five per cent of patients had satisfactory fracture reduction in ED (95% CI 59%-70%). Eighty-six patients underwent a secondary procedure to reduce/stabilise their fracture (28%, 95% CI 23%-33%). Younger age, lack of satisfactory ED reduction and increased number of instability factors were independently predictive of the performance of a secondary procedure. CONCLUSION: Instability risk factors are common in patients with wrist fractures requiring reduction in ED. The number of instability factors is not a strong predictor of the performance of secondary procedures.
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ItemCompliance with a COPD bundle of care in an Australian emergency department: A cohort study(WILEY, 2018-02)INTRODUCTION: Bundles of care are gaining popularity for treating acute severe illness. OBJECTIVE: To describe compliance with bundle of care elements (individually and as a "bundle") for patients treated for chronic obstructive pulmonary disease (COPD) exacerbations in the emergency department (ED). METHODS: Retrospective observational study of patients presenting in the 2014 calendar year with an ED diagnosis of COPD. The primary outcomes of interest were compliance with key bundle of care elements (individually and as a "bundle"). Analysis is descriptive. RESULTS: 381 patients were studied. Median age was 71 (IQR 64-80), 60% were male and 77% arrived by ambulance. Median duration of symptoms was 3 days (IQR 2-6 days). Compliance with the bundle elements was 90% for administration of controlled oxygen therapy (if oxygen given), 87% for administration of inhaled bronchodilators, 79% for administration of systemic corticosteroids, 75% of administration of antibiotics if evidence of infection, 77% for taking of a blood gas in non-mild disease, 98% for taking of a chest X-ray, and 74% for administration of NIV if pH <7.3. Compliance with all appropriate elements of the defined bundle of care was 49%. There was no difference in mean length of stay for admitted patients (P = .44), in-hospital mortality (P = 1.00) or re-admission within 30 days (P = .72) by bundle compliance. CONCLUSION: Compliance with individual assessment and treatment recommendations was generally high; however, compliance with the overall recommended bundle was only 49%. This indicates that there is an opportunity to improve care in these patients.