De novo and recurrent metastatic breast cancer - A systematic review of population-level changes in survival since 1995.

BACKGROUND: Advances in breast cancer (BC) care have reduced mortality, but their impact on survival once diagnosed with metastasis is less well described. This systematic review aimed to describe population-level survival since 1995 for de novo metastatic BC (dnMBC) and recurrent MBC (rMBC). METHODS: We searched MEDLINE 01/01/1995-12/04/2021 to identify population-based cohort studies of MBC reporting overall (OS) or BC-specific survival (BCSS) over time. We appraised risk-of-bias and summarised survival descriptively for MBC diagnoses in 5-year periods from 1995 until 2014; and for age, hormone receptor and HER2 subgroups. FINDINGS: We identified 20 eligible studies (14 dnMBC, 1 rMBC, 5 combined). Potential sources of bias in these studies were confounding and shorter follow-up for the latest diagnosis period.For dnMBC, 13 of 14 studies reported improved OS or BCSS since 1995. In 2005-2009, the median OS was 26 months (range 24-30), a median gain of 6 months since 1995-1999 (range 0-9, 4 studies). Median 5-year OS was 23% in 2005-2009, a median gain of 7% since 1995-1999 (range -2 to 14%, 4 studies). For women ≥70 years, the median and 5-year OS was unchanged (1 study) with no to modest difference in relative survival (range: -1·9% (p = 0.71) to +2·1% (p = 0.045), 3 studies). For rMBC, one study reported no change in survival between 1998 and 2006 and 2007-2013 (median OS 23 months). For combined MBC, 76-89% had rMBC. Three of four studies observed no change in median OS after 2000. Of these, one study reported median OS improved for women ≤60 years (1995-1999 19·1; 2000-2004 22·3 months) but not >60 years (12·7, 11·6 months). INTERPRETATION: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. FUNDING: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21-001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).

What proportion of patients with chronic noncancer pain are prescribed an opioid medicine? Systematic review and meta-regression of observational studies.

Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.

Health-related predictors of cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain. METHODS: A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared individuals with incident registry-notified CUP (n = 327; 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk. CONCLUSION: Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.

Demographic, social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. METHODS: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers. CONCLUSION: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.

Identifying incident cancer cases in dispensing claims: A validation study using Australia's Repatriation Pharmaceutical Benefits Scheme (PBS) data.

INTRODUCTION: Dispensing claims are used commonly as proxy measures in pharmacoepidemiological studies; however, their validity is often untested. OBJECTIVES: To assess the performance of a proxy for identifying cancer cases based on the dispensing of anticancer medicines and estimate the misclassification of cancer status and potential for bias researchers may encounter when using this proxy. METHODS: We conducted our validation study using Department of Veterans' Affairs (DVA) client data linked with the New South Wales (NSW) Cancer Registry and Repatriation Pharmaceutical Benefits Scheme data. We included DVA clients aged ≥65 years residing in NSW between July 2004 and December 2012. We matched clients with a cancer diagnosis to clients without a diagnosis based on demographic characteristics and available observation time. We used dispensing claims for anticancer medicines dispensed between July 2004 and December 2013 as a proxy to identify clients with cancer and calculated sensitivity, specificity, positive predictive values and negative predictive values compared with cancer registrations (gold standard), overall and by cancer site. We illustrated misclassification by the proxy in a cohort of people initiating opioid therapy. Using the proxy, we excluded people with cancer from the cohort, in an attempt to delineate people potentially using opioids for cancer rather than chronic non-cancer pain. RESULTS: We identified 15,679 new cancer diagnoses in 14,112 DVA clients from the cancer registry and 62,663 clients without a diagnosis. Sensitivity of the proxy based on dispensing claims was 30% for all cancers and around 20% for specific cancers (range: 10-67%). Specificity was above 90% for all cancers. The dispensing proxy correctly identified 26% of people with a cancer diagnosis who initiated opioid therapy and failed to identify 74% those with a cancer diagnosis; the proxy was most robust for clients with breast cancer where 61% were correctly identified by proxy. CONCLUSIONS: Using dispensing of anticancer medicines to identify people with a cancer diagnosis performed poorly. Excluding patients with evidence of anticancer medicine use from cohort studies may result removal of a disproportionate number of women with breast cancer. Researchers excluding or otherwise using anticancer medicine dispensing to identify people with cancer in pharmacoepidemiological studies should acknowledge the potential biases introduced to their findings. KEYWORDS: cancer, diagnosis, proxy, dispensing records, validation study.

Implementing a web-based oncology protocol system in Australia: evaluation of the first 3 years of operation.

BACKGROUND: EviQ is a web-based oncology protocol system launched across Australia in 2005 (http://www.eviq.org.au). We evaluated eviQ use at the point-of-care and determined the factors impacting on its uptake and routine use in the first three years of operation. METHODS: We conducted a suite of qualitative and quantitative studies with over 200 Australian oncology physicians, nurses and pharmacists working at treatment centres in diverse geographical locations. RESULTS: EviQ was part of routine care at many hospitals; however, the way in which it was used at the point-of-care varies according to clinician roles and hospital location. We identified a range of factors impacting on eviQ uptake and routine use. Infrastructure, such as availability of point-of-care computers, and formal policies endorsing eviQ are fundamental to increasing uptake. Furthermore, the level of clinical and computer experience of end-users, the attitudes and behaviour of clinicians, endorsement and promotion strategies, and level and type of eviQ education all need to be considered and managed to ensure that the system is being used to its full potential. CONCLUSION: Our findings show that the dissemination of web-based treatment protocols does not guarantee widespread use. Organisational, environmental and clinician-specific factors play a role in uptake and utilisation. The deployment of sufficient computer infrastructure, implementation of targeted training programmes and hospital policies and investment in marketing approaches are fundamental to uptake and continued use. This study highlights the value of ongoing monitoring and evaluation to ensure systems like eviQ achieve their primary purpose - reducing treatment variation and improving quality of care.

Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer.

BACKGROUND: Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. AIM: To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. METHODS: We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. RESULTS: Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. CONCLUSION: The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting.

Governance approval for multisite, non-interventional research: what can Harmonisation of Multi-Centre Ethical Review learn from the New South Wales experience?

BACKGROUND: In 2007, New South Wales Health mandated the separation of ethical and scientific review from research governance at all New South Wales public health sites based on their distinction in the National Health and Medical Research Council National Statement. This separation allowed for single-site ethical review of multicentre studies. AIMS: To investigate the time taken for governance approval of multicentre studies through the site-specific approval (SSA) process. METHODS: A retrospective audit of the SSA process for five non-interventional studies proposed by a university cancer research unit. RESULTS: The median total governance approval time for all submissions (n= 28) was 12 weeks (range 2.5-64); median time from starting the SSA to submission was 8 weeks (range 1-48) and median time for governance approval was 5 weeks (range 0.3-40). Approval times were shorter for public compared to private institutions. Reasons for delays in finalising submissions for approval were the absence of institutional governance officers, lack of clarity regarding signatories, the need to identify a principal investigator employed by the institution, and lack of recognition of ethical approval by private institutions. The need to develop legal agreements between the university and hospital was the main reason for lengthy delays in obtaining approval. CONCLUSIONS: The advantages of a harmonised single ethical review process were undermined by the coexistence of a fragmented, complex and lengthy governance approval process. This experience has implications for the success of the national Harmonisation of Multi-Centre Ethical Review (HoMER) model. A harmonised and fully supported national approach to research governance should be developed contemporaneously with HoMER.

The quality of web-based oncology guidelines and protocols: how do international sites stack up?

BACKGROUND: The Internet is a popular medium for disseminating information relevant to oncology practitioners. Despite the widespread use of web-based guidelines and protocols, the quality of these resources has not been evaluated. This study addresses this gap. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument was used to assess the quality of breast and sarcoma guidelines and protocols according to six independent domains. The oncology resources were selected from eight websites developed for healthcare settings in North America, the United Kingdom, Europe, and Australia. RESULTS: Mean quality scores across domains were highly variable for both guidelines (29-73%) and protocols (31-71%). Guidelines scored highly in terms of articulating their Scope and Purpose (72.6 ± 11.2%) but poorly with respect to Applicability in clinical practice (29.0 ± 17.3%). Protocols scored highly on Clarity of Presentation (70.6 ± 17.6%) but poorly in terms of the processes used to synthesise underlying evidence, develop, and update recommendations (30.8 ± 20.0%). CONCLUSION: Our evaluation provides a quick reference tool for clinicians about the strengths and limitations of oncology resources across several major websites. Further, it supports resource developers in terms of where to direct efforts to enhance guideline and protocol development processes or the communication of these processes to end-users.

Patterns of analgesic and anti-inflammatory medicine use by Australian veterans.

BACKGROUND: We examined analgesic and anti-inflammatory medicine use by Australian veterans before and after the introduction of selective Cox-2 inhibitors. METHODS: We studied cohorts of Gold Card-holding veterans using prescription data held by the Department of Veterans' Affairs for the period 1 July 1998 to 30 June 2004. Outcomes were volume dispensed, average daily quantity and cumulative incidence of use of paracetamol-containing and aspirin-containing medicines, non-selective and Cox-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and dextropropoxyphene. RESULTS: Overall, we found high levels of use of analgesic and anti-inflammatory medicines, which increased by 43% over the study period. Use of paracetamol-containing medicines was overtaken by NSAIDs in 1999/2000, corresponding to the introduction of the Cox-2-selective agents. Between 12 and 17% of Cox-2-selective medicine recipients were supplied amounts indicative of continuous use in relatively high doses and 51% of veterans received at least one relatively Cox-2-selective medicine (celecoxib, rofecoxib, meloxicam, diclofenac) by the end of the study period. Dextropropoxyphene use declined during the study and tramadol use increased 10-fold. CONCLUSION: This study shows very high levels of Cox-2 inhibitor use during the 6-year period. Cox-2-selective agents were more likely to be taken continuously and at higher doses than non-selective NSAIDs. This is relevant in view of the cardiovascular toxicity of this group of medicines. The study shows the value of using unit record dispensing data to assess drug use patterns. Linking dispensing records to hospital separation and mortality data will further enhance our ability to monitor drug safety.

Information sources used by New South Wales cancer clinicians: a qualitative study.

BACKGROUND: This study identified (i) information sources used by cancer clinicians to guide pharmacological treatments, (ii) utilization of, and opinions about, online information sources and (iii) clinicians' ability to access a specific cancer treatment protocol (escalated bleomycin, etiposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) for Hodgkin's Lymphoma). The work was carried out before activation of the Cancer Institute New South Wales Standard Cancer Treatment (CI-SCaT) programme. METHODS: We conducted semistructured interviews with a purposeful sample of senior and junior doctors, nurses and pharmacists treating adult cancer patients (n = 32) in eight New South Wales public hospitals. RESULTS: Information seeking processes are context specific and vary from clinician to clinician and ward to ward. Clinicians use human, electronic and printed information sources at, or close to, the point of patient care; however, experienced colleagues are preferred where information is needed quickly or in unfamiliar clinical situations. Barriers to using online cancer information are environmental (hardware, connection speeds, time), personal (poor computer literacy and lack of awareness of appropriate sites) and economic (costs of journal subscriptions). Just over half of participants were able to locate a specific cancer protocol and none of these protocols was fully consistent with CI-SCaT recommendations. CONCLUSION: There is no standardized approach to the pharmacological treatment of cancer patients in this sample of New South Wales clinicians. CI-SCaT will fill a gap with respect to standardizing oncology treatment. However, to ensure maximal CI-SCaT uptake, implementation plans should harness positive behavioural influences and attempt to modify the negative forces that act on hospital clinicians in their day-to-day work.

Graduate entry to medical school? Testing some assumptions.

BACKGROUND: Debate abounds regarding the most appropriate candidates to admit to medical school. This paper examines whether there is any advantage to admitting 'graduate' entrants over secondary school leavers on selected medical school and practice outcomes. AIM: To compare the medical school experiences, research and academic achievements and practice outcomes of graduates who entered 1 medical school in Australia directly from high school (secondary school entry) to those of graduates who entered with tertiary level education (tertiary entry). DESIGN AND METHODS: Cross-sectional study using a mail-out survey to graduates from the first 16 graduating years (1983-98 inclusive) of the University of Newcastle Medical School. RESULTS: Secondary school entrants were, on average, 8 years younger than tertiary entrants and were less likely to have received rural-based schooling. However, there were no differences with respect to gender or type of secondary school attended (public or private). Motivations for studying medicine did not generally differ according to entry type, except that more secondary students were motivated by parental expectations and more tertiary entrants were motivated by the need for professional independence and the desire to prevent disease. A greater proportion of tertiary entrants experienced stress at medical school. However, secondary students experienced more stress due to doubts about being a doctor, while tertiary entrants experienced more stress due to lack of leisure time, finances and balancing commitments. There were no significant differences between the groups in terms of academic performance (as measured by the award of medical school honours) or research outcomes (as measured by completion of a research degree during or after medical school training, publication of scientific papers or holding career posts in the research sciences). There were no differences in career positions held by clinicians, choice of general practice or another specialty as a career, practice location (rural or urban) or employment sector (public or private). CONCLUSION: There is no clear advantage, at least on the outcomes measured in this study, to limiting medical school entry to either those candidates from secondary school or those with tertiary backgrounds. Medical schools could reasonably broaden their selection criteria to include more graduate entry candidates in addition to secondary school leavers without compromising medical school and practice outcomes.

Which common clinical conditions should medical students be able to manage by graduation? A perspective from Australian interns.

The objectives of the study were to report the development of a core curriculum that details the clinical conditions medical students should be able to manage upon graduation; and to canvass the opinion of interns (first-year postgraduate doctors) regarding their perceptions of the level of skill required to manage each condition. Literature relating to core curriculum development and training of junior medical officers was reviewed and stakeholders in the education and training of medical students and junior doctors in the state of New South Wales, Australia (intern supervisors, academics, registrars, nurses and interns) were consulted. The final curriculum spanned 106 conditions, 77 'differentiated' and 29 'undifferentiated'. Four levels of skill at which conditions should potentially be managed were also identified: 'Theoretical knowledge only'; 'Recognize symptoms and signs without supervision'; Initiate preliminary investigations, management and/or treatment without supervision'; and 'Total investigation, management and/or treatment without supervision'. The list of conditions in the curriculum was converted to a survey format and a one-in-two random sample of interns (n = 193) practising in New South Wales who graduated from the state's three medical schools were surveyed regarding the level of skill required for managing each clinical condition at graduation. A total of 51.3% of interns responded to the survey. Interns felt they should be able to initiate preliminary investigation, management and/or treatment for most conditions in the curriculum, with more than half acknowledging this level of management for 53 of the differentiated and 28 of the undifferentiated conditions. It is concluded that developing core curricula in medical education can involve multiple stakeholders, including junior doctors as the consumers of educational experiences. The data gathered may be useful to medical schools revising their curricula.

The relationship between previous tertiary education and course performance in first year medical students at Newcastle University, Australia.

AIM: The purpose of this study was to identify the relationship between previous tertiary education background and the performance of first year medical students at Newcastle University, Australia. Specifically, we examined degree type (i.e. arts, science, allied health, nursing or other professional backgrounds), level of degree completion (fully or partially completed ), academic achievement ( grade point average) and whether or not students had postgraduate qualifications. The relationship between age and gender was also examined. METHOD: All students admitted to the medical course from 1990 to 1998 with previous tertiary education experience who entered via the "standard" entry pathway and sat the end of year examinations were eligible for the study (N=303). The outcome measures were the results of first assessment ("satisfactory" versus "not satisfactory") and final assessment of the first year ("satisfactory" versus "not satisfactory"). Logistic regression was used to examine the relationship between predictor variables and outcomes. RESULTS: In relation to first assessment results, students with a nursing and arts background were significantly more likely to receive a "not satisfactory" assessment (RR=3.9, 95% CI: 1.6- 7.7; RR=2.9, 95% CI: 1.2-6.8, respectively), as were females (RR=1.8, 95% CI: 1.1-3.5) and students with a grade point average of less than a distinction average (RR=2.8, 95% CI: 1.6-5.2). At final assessment, students with a nursing background and those with a less than distinction average were more likely to receive a "not satisfactory" result (RR=20.7, 95% CI: 3.5-123.9 and RR=4.0, 95% CI: 1.2-13.9, respectively); consequently, they were required to repeat first year. CONCLUSION: Our research suggests that there are some medical student groups who encounter more academic difficulties than others in first year. Identifying these students can assist medical schools to focus academic support appropriately.

How do Australian doctors with different pre-medical school backgrounds perform as interns?

AIM: To assess whether there is any advantage to be gained with respect to performance in the first year of postgraduate medical training (internship) by selecting medical school candidates with different educational backgrounds. Specifically, we were interested in comparing the performance ratings of interns who entered medical school with secondary (directly from high school) or tertiary (at least one year of a university degree) level educational backgrounds. FOCUS: We compared the performance ratings of interns according to the subjects or degree undertaken at a secondary or tertiary level, respectively. The effects of age and gender were also examined to determine their influence on performance ratings. METHOD: All graduates (N=235) from the University of Newcastle Medical School, Australia who commenced their intern year in the state of New South Wales from 1993 to 1996 inclusive were eligible for the study. The outcome measure was a score derived from a valid and reliable clinical supervisor rating scale. Independent variables were level of previous educational experience (secondary or tertiary entry), and subjects studied by secondary level entrants (predominantly science or equal proportions of humanities and science) and degree undertaken by tertiary level entrants (arts or science or allied health or nursing). RESULTS: The records of 173 (73% of eligible sample) were included in the analyses. There were no significant differences between the mean ratings of interns with respect to previous educational background, subjects studied at secondary school or degree undertaken. Age and gender did not significantly affect performance ratings.

Factors affecting progress of Australian and international students in a problem-based learning medical course.

CONTEXT: Research on the factors affecting progress in medical schools has typically focused on mainstream (non-Indigenous Australian, non-international) students in traditional, didactic programmes. These results may not be applicable to students, particularly those from culturally diverse backgrounds, undertaking problem-based learning courses. OBJECTIVE: This study used qualitative methodology to explore and compare factors affecting progress for mainstream Australian students (non-Indigenous Australian, non-international) and international students (full fee-paying students who had relocated countries to study) in a problem-based learning medical course. Intervention strategies were devised on the basis of the participants' experiences. METHODS: Six focus group discussions were conducted (three with mainstream Australian and three with international participants). Transcripts of these discussions were coded and analysed independently by two researchers and discussed until consensus was attained. RESULTS: Participants identified both positive and negative experiences related to the course structure, which were consistent with previous findings. The participants' experiences demonstrated a relationship between sense of 'belongingness' to the medical school community, participation in learning opportunities and progress through the course. CONCLUSIONS: The results suggest that interventions aimed at reducing barriers to progress need to promote students' confidence, motivation and subsequent participation in course learning opportunities. These results have application to other problem-based learning courses particularly those which face the challenge of providing an optimal learning environment for students from diverse backgrounds.

A binary adenoviral vector system for expressing high levels of the proapoptotic gene bax.

The bax gene plays a critical role in signaling apoptosis and expression through gene transfer may be valuable in the treatment of a variety of apoptosis-related diseases such as cancer. However, constructing an adenoviral vector expressing a bax gene driven by a constitutive promoter has been difficult, presumably because of the gene's high proapoptotic activity. Here we report a system that induces the expression of the bax gene safely by adenovirus-mediated gene cotransfer. Briefly, the system involves an adenoviral vector containing a human bax cDNA driven by a synthetic promoter consisting of five GAL4-binding sites and a TATA box (GT). This vector expresses a minimal background level of bax protein in cultured mammalian cells thus preventing apoptosis of packaging cells, however, expression of the bax gene can be induced substantially in vitro and in vivo by transferring it into target cells along with an adenoviral vector expressing the transactivator, fusion protein GAL4/VP16. Extensive apoptosis was observed after induction of the bax gene both in cultured human lung carcinoma cells and in the livers of Balb/c mice. Our results suggest that this GAL4 gene regulatory system provides an alternative approach to constructing viral vectors that express potentially toxic genes. Gene Therapy (2000) 7, 75-79.

Impact of written information on knowledge and preferences for cardiopulmonary resuscitation.

AIM: To investigate knowledge about and attitudes to cardiopulmonary resuscitation (CPR), and to determine whether written information about CPR alters knowledge and choices made. DESIGN: Questionnaire-based survey before and immediately after provision of written information describing CPR and its risks and benefits. SUBJECTS AND SETTING: All health professionals (803) and competent inpatients (260) in a tertiary care hospital (John Hunter Hospital, Newcastle, New South Wales, Australia) in June 1994. MAIN OUTCOME MEASURES: CPR knowledge scores and choice scores (number of hypothetical clinical scenarios in which CPR would be chosen) before and after provision of information about CPR. RESULTS: Response rates were 64% (health professionals) and 58% (patients). Patients had limited awareness of procedures involved in CPR, while both patients and health professionals overestimated its success rates. Mean knowledge scores increased after provision of information: for patients, from 6.4 out of 18 (95% confidence interval [CI], 6.0-6.9) to 10.4 (95% CI, 9.9-11.1); and for health professionals, from 11.9 (95% CI, 11.7-12.1) to 13.9 (95% CI, 13.7-14.2). In contrast, mean choice scores decreased after provision of information: for patients, from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8); and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). CONCLUSION: Our results imply that people understand and use prognostic information to make decisions about CPR. To make autonomous judgements, patients and health professionals need better education on CPR outcomes.