Medicine (RMH) - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 11
-
ItemEvaluation of models to predict BRCA germline mutations(NATURE PUBLISHING GROUP, 2006-10-09)The selection of candidates for BRCA germline mutation testing is an important clinical issue yet it remains a significant challenge. A number of risk prediction models have been developed to assist in pretest counselling. We have evaluated the performance and the inter-rater reliability of four of these models (BRCAPRO, Manchester, Penn and the Myriad-Frank). The four risk assessment models were applied to 380 pedigrees of families who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model. Using a greater than 10% probability threshold, the likelihood that a BRCA test result was positive in a mutation carrier compared to the likelihood that the same result would be expected in an individual without a BRCA mutation was 2.10 (95% confidence interval (CI) 1.66-2.67) for Penn, 1.74 (95% CI 1.48-2.04) for Myriad, 1.35 (95% CI 1.19-1.53) for Manchester and 1.68 (95% CI 1.39-2.03) for BRCAPRO. Application of these models, therefore, did not rule in BRCA mutation carrier status. Similar trends were observed for separate BRCA1/2 performance measures except BRCA2 assessment in the Penn model where the positive likelihood ratio was 5.93. The area under the ROC curve for each model was close to 0.75. In conclusion, the four models had very little impact on the pre-test probability of disease; there were significant clinical barriers to using some models and risk estimates varied between experts. Use of models for predicting BRCA mutation status is not currently justified for populations such as that evaluated in the current study.
-
ItemEfficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures: a randomised controlled trial [ACTRN012605000079640](BIOMED CENTRAL LTD, 2008-11-25)BACKGROUND: Vertebroplasty is a promising but as yet unproven treatment for painful osteoporotic vertebral fractures. It involves radiographic-guided injection of various types of bone cement directly into the vertebral fracture site. Uncontrolled studies and two controlled quasi-experimental before-after studies comparing volunteers who were offered treatment to those who refused it, have suggested an early benefit including rapid pain relief and improved function. Conversely, several uncontrolled studies and one of the controlled before-after studies have also suggested that vertebroplasty may increase the risk of subsequent vertebral fractures, particularly in vertebrae adjacent to treated levels or if cement leakage into the adjacent disc has occurred. As yet, there are no completed randomised controlled trials of vertebroplasty for osteoporotic vertebral fractures. The aims of this participant and outcome assessor-blinded randomised placebo-controlled trial are to i) determine the short-term efficacy and safety (3 months) of vertebroplasty for alleviating pain and improving function for painful osteoporotic vertebral fractures; and ii) determine its medium to longer-term efficacy and safety, particularly the risk of further fracture over 2 years. DESIGN: A double-blind randomised controlled trial of 200 participants with one or two recent painful osteoporotic vertebral fractures. Participants will be stratified by duration of symptoms (< and >or= 6 weeks), gender and treating radiologist and randomly allocated to either the treatment or placebo. Outcomes will be assessed at baseline, 1 week, 1, 3, 6, 12 and 24 months. Outcome measures include overall, night and rest pain on 10 cm visual analogue scales, quality of life measured by the Assessment of Quality of Life, Osteoporosis Quality of Life and EQ-5D questionnaires; participant perceived recovery on a 7-point ordinal scale ranging from 'a great deal worse' to 'a great deal better'; disability measured by the Roland-Morris Disability Questionnaire; timed 'Up and Go' test; and adverse effects. The presence of new fractures will be assessed by radiographs of the thoracic and lumbar spine performed at 12 and 24 months. DISCUSSION: The results of this trial will be of major international importance and findings will be immediately translatable into clinical practice.
-
ItemMagnitude and meaningfulness of change in SF-36 scores in four types of orthopedic surgery(BMC, 2008-07-31)BACKGROUND: The Medical Outcomes General Health Survey (SF-36) is a widely used health status measure; however, limited evidence is available for its performance in orthopedic settings. The aim of this study was to examine the magnitude and meaningfulness of change and sensitivity of SF-36 subscales following orthopedic surgery. METHODS: Longitudinal data on outcomes of total hip replacement (THR, n = 255), total knee replacement (TKR, n = 103), arthroscopic partial meniscectomy (APM, n = 74) and anterior cruciate ligament reconstruction (ACL, n = 62) were used to estimate the effect sizes (ES, magnitude of change) and minimal detectable change (sensitivity) at the group and individual level. To provide context for interpreting the magnitude of changes in SF-36 scores, we also compared patients' scores with age and sex-matched population norms. The studies were conducted in Sweden. Follow-up was five years in THR and TKR studies, two years in ACL, and three months in APM. RESULTS: On average, large effect sizes (ES> or =0.80) were found after orthopedic surgery in SF-36 subscales measuring physical aspects (physical functioning, role physical, and bodily pain). Small (0.20-0.49) to moderate (0.50-0.79) effect sizes were found in subscales measuring mental and social aspects (role emotional, vitality, social functioning, and mental health). General health scores remained relatively unchanged during the follow-up. Despite improvements, post-surgery mean scores of patients were still below the age and sex matched population norms on physical subscales. Patients' scores on mental and social subscales approached population norms following the surgery. At the individual level, scores of a large proportion of patients were affected by floor or ceiling effects on several subscales and the sensitivity to individual change was very low. CONCLUSION: Large to moderate meaningful changes in group scores were observed in all SF-36 subscales except General Health across the intervention groups. Therefore, in orthopedic settings, the SF-36 can be used to show changes for groups in physical, mental, and social dimensions and in comparison with population norms. However, SF-36 subscales have low sensitivity to individual change and so we caution against using SF-36 to monitor the health status of individual patients undergoing orthopedic surgery.
-
ItemParsimonious and efficient assessment of health-related quality of life in osteoarthritis research: validation of the Assessment of Quality of Life (AQoL) instrument(BMC, 2006-03-23)BACKGROUND: The Assessment of Quality of Life (AQoL) utility instrument was psychometrically developed for the general population. This study aimed to explore its potential as an osteoarthritis (OA) outcome measure. METHODS: WOMAC, Lequesne index, SF-36, Visual analogue scales and the AQoL were administered to 222 people with OA. The ability of each questionnaire to detect differences between groups was based on (i) self-rated health (SRH) and, (ii) differences between people on an orthopedic waiting list (WL) vs people with OA in the community (C). Comparisons included effect size, relative efficiency and receiver operator characteristic curves. RESULTS: All instruments detected differences between groups; however no one instrument exhibited superior efficiency. The AQoL demonstrated strong psychometric properties. CONCLUSION: The AQoL has equivalent performance to comparator questionnaires commonly used in OA research and would be a useful adjunct to well-established disease specific scales. The AQoL has important advantages; brevity (12 items), facilitates comparisons between disease groups, and delivers a utility score that can be used in health economic evaluations.
-
ItemEffects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial(BMC, 2007-09-24)BACKGROUND: Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. METHODS/DESIGN: Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. DISCUSSION: Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. TRIAL REGISTRATION: ACTR12605000503628; NCT00415259.
-
ItemAnalysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource(BMC, 2006)INTRODUCTION: The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comprehensive resource of epidemiological and clinical data with biospecimens from individuals at high risk of breast and/or ovarian cancer, and from their close relatives. METHODS: Epidemiological, family history and lifestyle data, as well as biospecimens, are collected from multiple-case breast cancer families ascertained through family cancer clinics in Australia and New Zealand. We used the Tyrer-Cuzick algorithms to assess the prospective risk of breast cancer in women in the kConFab cohort who were unaffected with breast cancer at the time of enrolment in the study. RESULTS: Of kConFab's first 822 families, 518 families had multiple cases of female breast cancer alone, 239 had cases of female breast and ovarian cancer, 37 had cases of female and male breast cancer, and 14 had both ovarian cancer as well as male and female breast cancer. Data are currently held for 11,422 people and germline DNAs for 7,389. Among the 812 families with at least one germline sample collected, the mean number of germline DNA samples collected per family is nine. Of the 747 families that have undergone some form of mutation screening, 229 (31%) carry a pathogenic or splice-site mutation in BRCA1 or BRCA2. Germline DNAs and data are stored from 773 proven carriers of BRCA1 or BRCA1 mutations. kConFab's fresh tissue bank includes 253 specimens of breast or ovarian tissue--both normal and malignant--including 126 from carriers of BRCA1 or BRCA2 mutations. CONCLUSION: These kConFab resources are available to researchers anywhere in the world, who may apply to kConFab for biospecimens and data for use in ethically approved, peer-reviewed projects. A high calculated risk from the Tyrer-Cuzick algorithms correlated closely with the subsequent occurrence of breast cancer in BRCA1 and BRCA2 mutation positive families, but this was less evident in families in which no pathogenic BRCA1 or BRCA2 mutation has been detected.
-
ItemNo Preview AvailableSeverely compromised quality of life in women and those of lower socioeconomic status waiting for joint replacement surgery(WILEY-LISS, 2005-10-15)OBJECTIVE: To determine health-related quality of life (HRQOL), psychological distress, physical function, and self efficacy in persons waiting for lower-limb joint replacement surgery. METHODS: A total of 214 patients on a waiting list for unilateral primary total knee or hip replacement at a large Australian public teaching hospital completed questionnaires after entry to the list. HRQOL and psychological distress were compared with available population norms. RESULTS: Average HRQOL was extremely poor (mean +/- SD 0.39 +/- 0.24) and much lower (>2 SD) than the population norm. Near death-equivalent HRQOL or worse than death-equivalent HRQOL were reported by 15% of participants. High or very high psychological distress was up to 5 times more prevalent in the waiting list sample (relative risk 5.4 for participants ages 75 years and older; 95% confidence interval 3.3, 9.0). Women had significantly lower HRQOL, self efficacy, and physical function scores than men. After adjusting for age and sex, significant socioeconomic disparities were also found. Participants who received the lowest income had the poorest HRQOL; those with the least education or the lowest income had the highest psychological distress. Low self efficacy was moderately associated with poor HRQOL (r = 0.49, P < 0.001) and more strongly associated with high psychological distress (r = -0.55, P < 0.001). CONCLUSION: Patients waiting for joint replacement have very poor HRQOL and high psychological distress, especially women and those from lower socioeconomic backgrounds. Lengthy waiting lists mean patients can experience extended and potentially avoidable morbidity. Interventions to address psychological distress and self efficacy could reduce this burden and should target women and lower socioeconomic groups.
-
ItemNo Preview AvailableIntegrating data to facilitate clinical research: a case study.(Portico, 2005)The integration of routine clinical administrative activities into ongoing rigorous clinical research poses challenges for both clinicians and researchers. This case study describes the development of a responsive database system used to facilitate comprehensive longitudinal research into the outcomes of patients waiting for hip and knee replacement surgery in a large public teaching hospital. The initial research procedure was paper-based, with manual patient matching and data entry. This process was time-consuming and associated with substantial risk of error and omissions, necessitating the design of a better system. An integrated database system was designed to receive daily electronic updates of the orthopaedic waiting-list and scheduled clinic and surgery dates. Using readily available software (Microsoft Access), new patients were identified through specifying inclusion and exclusion criteria which allowed rapid and complete recruitment at time of entry to the waiting-list. The integrated system specified the appropriate timing of multiple follow-up assessments, provided prompt information on recruitment for reporting purposes and integrated multiple linked research projects within one database. Seamless exporting of data to statistical programs for analysis was also enabled. This simple integrated approach facilitated efficient execution of a longitudinal study from recruitment to statistical analysis while maximising confidentiality and minimising resources required. This case study describes the development and design of a simple system which could be easily adapted for database management in hospital or clinic-based settings according to local requirements.
-
ItemNo Preview AvailableEvaluating quality of life in hip and knee replacement: Psychometric properties of the world health organization quality of life short version instrument(WILEY-LISS, 2006-08-15)OBJECTIVE: To evaluate the psychometric properties of the World Health Organization Quality of Life short version instrument (WHOQOL-BREF), and to determine its responsiveness in assessing early outcome after total hip or knee replacement surgery. METHODS: At baseline (entry to an orthopedic waiting list), 279 participants completed the WHOQOL-BREF instrument, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Assessment of Quality of Life (AQOL) instrument, Kessler Psychological Distress (K10) scale, and the modified Health Assessment Questionnaire (MHAQ). A total of 74 patients completed reassessments 3 months after surgery. RESULTS: The WHOQOL-BREF demonstrated acceptable internal consistency for all domains (Cronbach's alpha = 0.76-0.84) and moderate concurrent validity for the physical and psychological domains (r = 0.67 for physical versus AQOL; r = -0.71 for psychological versus K10). Minimal ceiling or floor effects were identified at baseline or 3 months, except for the social relationships domain. The disease-specific WOMAC subscales were most responsive to change (relative efficiency [RE] 0.66-1.00). Apart from social relationships, all WHOQOL-BREF scores improved significantly after surgery. The physical domain was more responsive than the AQOL (RE 0.50 versus 0.42) and was similar to the MHAQ (RE 0.55 for MHAQ). The responsiveness of the psychological domain was similar to that of the K10 scale (RE 0.11 versus 0.08). CONCLUSION: The WHOQOL-BREF has good psychometric properties for use in persons with severe joint disease, and by providing complementary information, it offers clinicians and researchers an additional tool for comprehensively assessing quality of life in this patient group.
-
ItemCan a disease-specific education program augment self-management skills and improve Health-Related Quality of Life in people with hip or knee osteoarthritis?(BMC, 2006-11-30)BACKGROUND: Patient education and self-management programs are offered in many countries to people with chronic conditions such as osteoarthritis (OA). The most well-known is the disease-specific Stanford Arthritis Self-Management Program (ASMP). While Australian and international clinical guidelines promote the concept of self-management for OA, there is currently little evidence to support the use of the ASMP. Several meta-analyses have reported that arthritis self-management programs had minimal or no effect on reducing pain and disability. However, previous studies have had methodological shortcomings including the use of outcome measures which do not accurately reflect program goals. Additionally, limited cost-effectiveness analyses have been undertaken and the cost-utility of the program has not been explored. METHODS/DESIGN: This study is a randomised controlled trial to determine the efficacy (in terms of Health-Related Quality of Life and self-management skills) and cost-utility of a 6-week group-based Stanford ASMP for people with hip or knee OA. Six hundred participants referred to an orthopaedic surgeon or rheumatologist for hip or knee OA will be recruited from outpatient clinics at 2 public hospitals and community-based private practices within 2 private hospital settings in Victoria, Australia. Participants must be 18 years or over, fluent in English and able to attend ASMP sessions. Exclusion criteria include cognitive dysfunction, previous participation in self-management programs and placement on a waiting list for joint replacement surgery or scheduled joint replacement.Eligible, consenting participants will be randomised to an intervention group (who receive the ASMP and an arthritis self-management book) or a control group (who receive the book only). Follow-up will be at 6 weeks, 3 months and 12 months using standardised self-report measures. The primary outcome is Health-Related Quality of Life at 12 months, measured using the Assessment of Quality of Life instrument. Secondary outcome measures include the Health Education Impact Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index (pain subscale and total scores), Kessler Psychological Distress Scale and the Hip and Knee Multi-Attribute Priority Tool. Cost-utility analyses will be undertaken using administrative records and self-report data. A subgroup of 100 participants will undergo qualitative interviews to explore the broader potential impacts of the ASMP. DISCUSSION: Using an innovative design combining both quantitative and qualitative components, this project will provide high quality data to facilitate evidence-based recommendations regarding the ASMP.