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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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The duration and cost of cancer clinical trials could be reduced if a surrogate endpoint were used in place of survival. We did a meta-analysis to assess the extent to which two surrogates, tumour response and time to progression, are predictive of mortality in metastatic colorectal cancer and non-small-cell lung cancer. METHODS: Summary data (median time to progression, proportion of patients responding to treatment, and median overall survival) from randomised trials of first-line treatment in colorectal cancer (146 trials) and lung cancer (191 trials) were identified. Data were extracted and analysed by linear regression. We used prediction bands for trials with 250, 500, and 750 patients to identify the surrogate threshold effect that would predict a significant difference in survival. FINDINGS: Response to treatment and time to progression correlated with improvement in survival for both lung cancer (p<0.0001 and p=0.0003, respectively) and colorectal cancer (p<0.0001 for both). To predict a significant survival gain in colorectal cancer trials, an improvement of 20% in the number of patients responding to treatment was required in trials with 750 patients, increasing to 26% in trials with 500 patients and 38% in trials with 250 patients. In lung cancer trials, the same prediction required differences in response of 18% for 750 patients, 21% for 500 patients, and 30% for 250 patients. For time to progression for both cancer types, the incremental gain needed to predict a survival improvement was a median of 1.8 months for trials with 750 patients, 2.2 months for 500 patients, and 3.3 months for 250 patients. INTERPRETATION: Irrespective of trial size, large differences in tumour response rate are needed to predict a significant survival benefit. If surrogates are chosen as the primary endpoint in a clinical trial, time to progression is the preferred measure because more modest and achievable differences are needed for a significant survival benefit. Trials in metastatic lung cancer and colorectal cancer should measure survival as their primary outcome unless the surrogate outcome difference is anticipated to exceed the threshold effect size. [ABSTRACT FROM AUTHOR]

Objectives: To survey interns regarding their opinion of medical school learning needs for a range of core skills. Methods: A random sample of interns practising in New South Wales, Australia, who graduated from the state's three medical schools were surveyed two-thirds of the way through their first hospital year. They were asked whether there was a need for further medical school education for each of 226 core skills. Skills were grouped into five themes: management of clinical conditions; clinical investigations; clinical procedures; core practice; and professional development. Results: Frequency distributions weighted for age, gender and medical school background were calculated for each item. The 20 most frequently identified needs related to examinations of the eye and ear, nose and throat; managing uncooperative patients and difficult patient interactions; prescribing; writing not for resuscitation orders and death certificates. Also included were procedural needs related to ear, nose and throat; plastering and wound management; and needs for more education in the management of clinical conditions related predominantly to ''acute'' cases such as anaphylaxis and diabetic ketoacidosis. Conclusion: Interns were able to discriminate between their needs for different skills and identified many core skills for which they perceived there was a need for more medical school education. The implications for medical education are discussed. [ABSTRACT FROM AUTHOR]

Cerebrovascular dysfunction is a hallmark feature of Alzheimer's disease (AD). One of the greatest risk factors for AD is the apolipoprotein E4 (E4) allele. The APOE4 genotype has been shown to negatively impact vascular amyloid clearance, however, its direct influence on the molecular integrity of the cerebrovasculature compared to other APOE variants (APOE2 and APOE3) has been largely unexplored. To address this, we employed a 10-plex tandem isobaric mass tag approach in combination with an ultra-high pressure liquid chromatography MS/MS (Q-Exactive) method, to interrogate unbiased proteomic changes in cerebrovessels from AD and healthy control brains with different APOE genotypes. We first interrogated changes between healthy control cases to identify underlying genotype specific effects in cerebrovessels. EIF2 signaling, regulation of eIF4 and 70S6K signaling and mTOR signaling were the top significantly altered pathways in E4/E4 compared to E3/E3 cases. Oxidative phosphorylation, EIF2 signaling and mitochondrial dysfunction were the top significant pathways in E2E2 vs E3/E3cases. We also identified AD-dependent changes and their interactions with APOE genotype and found the highest number of significant proteins from this interaction was observed in the E3/E4 (192) and E4/E4 (189) cases. As above, EIF2, mTOR signaling and eIF4 and 70S6K signaling were the top three significantly altered pathways in E4 allele carriers (i.e. E3/E4 and E4/E4 genotypes). Of all the cerebrovascular cell-type specific markers identified in our proteomic analyses, endothelial cell, astrocyte, and smooth muscle cell specific protein markers were significantly altered in E3/E4 cases, while endothelial cells and astrocyte specific protein markers were altered in E4/E4 cases. These proteomic changes provide novel insights into the longstanding link between APOE4 and cerebrovascular dysfunction, implicating a role for impaired autophagy, ER stress, and mitochondrial bioenergetics. These APOE4 dependent changes we identified could provide novel cerebrovascular targets for developing disease modifying strategies to mitigate the effects of APOE4 genotype on AD pathogenesis.

Background: Matrix metallopeptidase 9 (MMP9) has been implicated in a variety of neurological disorders, including Alzheimer's disease (AD), where MMP9 levels are elevated in the brain and cerebrovasculature. Previously our group demonstrated apolipoprotein E4 (apoE4) was less efficient in regulating MMP9 activity in the brain than other apoE isoforms, and that MMP9 inhibition facilitated beta-amyloid (Aβ) elimination across the blood-brain barrier (BBB) METHODS: In the current studies, we evaluated the impact of MMP9 modulation on Aβ disposition and neurobehavior in AD using two approaches, (1) pharmacological inhibition of MMP9 with SB-3CT in apoE4 x AD (E4FAD) mice, and (2) gene deletion of MMP9 in AD mice (MMP9KO/5xFAD) RESULTS: Treatment with the MMP9 inhibitor SB-3CT in E4FAD mice led to reduced anxiety compared to placebo using the elevated plus maze. Deletion of the MMP9 gene in 5xFAD mice also reduced anxiety using the open field test, in addition to improving sociability and social recognition memory, particularly in male mice, as assessed through the three-chamber task, indicating certain behavioral alterations in AD may be mediated by MMP9. However, neither pharmacological inhibition of MMP9 or gene deletion of MMP9 affected spatial learning or memory in the AD animals, as determined through the radial arm water maze. Moreover, the effect of MMP9 modulation on AD neurobehavior was not due to changes in Aβ disposition, as both brain and plasma Aβ levels were unchanged in the SB-3CT-treated E4FAD animals and MMP9KO/AD mice compared to their respective controls., Conclusions: In total, while MMP9 inhibition did improve specific neurobehavioral deficits associated with AD, such as anxiety and social recognition memory, modulation of MMP9 did not alter spatial learning and memory or Aβ tissue levels in AD animals. While targeting MMP9 may represent a therapeutic strategy to mitigate aspects of neurobehavioral decline in AD, further work is necessary to understand the nature of the relationship between MMP9 activity and neurological dysfunction.

Cerebrovascular dysfunction and cerebral amyloid angiopathy (CAA) are hallmark features of Alzheimer's disease (AD). Molecular damage to cerebrovessels in AD may result in alterations in vascular clearance mechanisms leading to amyloid deposition around blood vessels and diminished neurovascular-coupling. The sequelae of molecular events leading to these early pathogenic changes remains elusive. To address this, we conducted a comprehensive in-depth molecular characterization of the proteomic changes in enriched cerebrovessel fractions isolated from the inferior frontal gyrus of autopsy AD cases with low (85.5 ± 2.9 yrs) vs. high (81 ± 4.4 yrs) CAA score, aged-matched control (87.4 ± 1.5 yrs) and young healthy control (47 ± 3.3 yrs) cases. We employed a 10-plex tandem isobaric mass tag approach in combination with our ultra-high pressure liquid chromatography MS/MS (Q-Exactive) method. Enriched cerebrovascular fractions showed very high expression levels of proteins specific to endothelial cells, mural cells (pericytes and smooth muscle cells), and astrocytes. We observed 150 significantly regulated proteins in young vs. aged control cerebrovessels. The top pathways significantly modulated with aging included chemokine, reelin, HIF1α and synaptogenesis signaling pathways. There were 213 proteins significantly regulated in aged-matched control vs. high CAA cerebrovessels. The top three pathways significantly altered from this comparison were oxidative phosphorylation, Sirtuin signaling pathway and TCA cycle II. Comparison between low vs. high CAA cerebrovessels identified 84 significantly regulated proteins. Top three pathways significantly altered between low vs. high CAA cerebrovessels included TCA Cycle II, Oxidative phosphorylation and mitochondrial dysfunction. Notably, high CAA cases included more advanced AD pathology thus cerebrovascular effects may be driven by the severity of amyloid and Tangle pathology. These descriptive proteomic changes provide novel insights to explain the age-related and AD-related cerebrovascular changes contributing to AD pathogenesis. Particularly, disturbances in energy bioenergetics and mitochondrial biology rank among the top AD pathways altered in cerebrovessels. Targeting these failed mechanisms in endothelia and mural cells may provide novel disease modifying targets for developing therapeutic strategies against cerebrovascular deterioration and promoting cerebral perfusion in AD. Our future work will focus on interrogating and validating these novel targets and pathways and their functional significance., Competing Interests: JR was employed by company Boehringer Ingelheim Pharmaceuticals, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ojo, Reed, Crynen, Vallabhaneni, Evans, Shackleton, Eisenbaum, Ringland, Edsell, Mullan, Crawford and Bachmeier.)

A pathological characteristic of repetitive traumatic brain injury (TBI) is the deposition of hyperphosphorylated and aggregated tau species in the brain and increased levels of extracellular monomeric tau are believed to play a role in the pathogenesis of neurodegenerative tauopathies. The pathways by which extracellular tau is eliminated from the brain, however, remains elusive. The purpose of this study was to examine tau uptake by cerebrovascular cells and the effect of TBI on these processes. We found monomeric tau interacts with brain vascular mural cells (pericytes and smooth muscle cells) to a greater extent than other cerebrovascular cells, indicating mural cells may contribute to the elimination of extracellular tau, as previously described for other solutes such as beta-amyloid. Consistent with other neurodegenerative disorders, we observed a progressive decline in cerebrovascular mural cell markers up to 12 months post-injury in a mouse model of repetitive mild TBI (r-mTBI) and human TBI brain specimens, when compared to control. These changes appear to reflect mural cell degeneration and not cellular loss as no difference in the mural cell population was observed between r-mTBI and r-sham animals as determined through flow cytometry. Moreover, freshly isolated r-mTBI cerebrovessels showed reduced tau uptake at 6 and 12 months post-injury compared to r-sham animals, which may be the result of diminished cerebrovascular endocytosis, as caveolin-1 levels were significantly decreased in mouse r-mTBI and human TBI cerebrovessels compared to their respective controls. Further emphasizing the interaction between mural cells and tau, similar reductions in mural cell markers, tau uptake, and caveolin-1 were observed in cerebrovessels from transgenic mural cell-depleted animals. In conclusion, our studies indicate repeated injuries to the brain causes chronic mural cell degeneration, reducing the caveolar-mediated uptake of tau by these cells. Alterations in tau uptake by vascular mural cells may contribute to tau deposition in the brain following head trauma and could represent a novel therapeutic target for TBI or other neurodegenerative disorders., (Published by Elsevier Inc.)

Apolipoprotein E (APOE) has been shown to influence amyloid-β (Aβ) clearance from the brain in an isoform-specific manner. Our prior work showed that Aβ transit across the blood-brain-barrier was reduced by apoE4, compared to other apoE isoforms, due to elevated lipoprotein receptor shedding in brain endothelia. Recently, we demonstrated that matrix metallopeptidase 9 (MMP-9) induces lipoprotein receptor proteolysis in an apoE isoform-dependent manner, which impacts Aβ elimination from the brain. The current studies interrogated the relationship between apoE and MMP-9 and found that apoE impacted proMMP-9 cellular secretion from brain endothelia (apoE2 < apoE3 = apoE4). In a cell-free assay, apoE dose-dependently reduced MMP-9 activity, with apoE4 showing a significantly weaker ability to inhibit MMP-9 function than apoE2 or apoE3. Finally, we observed elevated MMP-9 expression and activity in the cerebrovasculature of both human and animal AD brain specimens with an APOE4 genotype. Collectively, these findings suggest a role for apoE in regulating MMP-9 disposition and may describe the effect of apoE4 on Aβ pathology in the AD brain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Lipoprotein receptor transport across the blood-brain barrier (BBB) mediates beta-amyloid (Aβ) accumulation in the brain and may be a contributing factor in Alzheimer's disease (AD) pathogenesis. Lipoprotein receptors are susceptible to proteolytic shedding at the cell surface, which precludes the endocytic transport of ligands. A ligand that closely interacts with the lipoprotein receptors is apolipoprotein E (apoE), which exists as three isoforms (apoE2, apoE3, apoE4). Our prior work showed an inverse relationship between lipoprotein receptor shedding and Aβ transport across the BBB, which was apoE-isoform dependent. To interrogate this further, the current studies investigated an enzyme implicated in lipoprotein receptor shedding, matrix metalloproteinase 9 (MMP9). Treatment with MMP9 dose-dependently elevated lipoprotein receptor shedding in brain endothelial cells and freshly isolated mouse cerebrovessels. Furthermore, treatment with a MMP9 inhibitor (SB-3CT) mitigated Aβ-induced lipoprotein receptor shedding in brain endothelial cells and the brains of apoE4 animals. In terms of BBB transit, SB-3CT treatment increased the transport of Aβ across an in vitro model of the BBB. In vivo, administration of SB-3CT to apoE4 animals significantly enhanced Aβ clearance from the brain to the periphery following intracranial administration of Aβ. The current studies show that MMP9 impacts lipoprotein receptor shedding and Aβ transit across the BBB, in an apoE  isoform-specific manner. In total, MMP9 inhibition can facilitate Aβ clearance across the BBB, which could be an effective approach to lowering Aβ levels in the brain and mitigating the AD phenotype, particularly in subjects carrying the apoE4 allele.

Objective: Pulmonary function abnormalities and hospital re-admissions in survivors of neonatal lung disease remain highly prevalent. The respiratory outcomes study (RESPOS) aimed to investigate the respiratory and associated atopy outcomes in preterm infants <30 weeks gestational age (GA) and/or birth-weight (BWt) <1000 g at primary school age, and to compare these outcomes between infants with and without chronic lung disease (CLD)., Methods: In the RESPOS 92 parents of preterm infants admitted to the Neonatal unit in Canberra Hospital between 1/1/2001 and 31/12/2003 were sent a questionnaire regarding their respiratory, atopy management and follow-up., Results: Fifty-three parents responded, including 28 preterm infants who had CLD and 25 who had no CLD. The gestational age was significantly lower in the CLD group compared to the non-CLD group [26.9 (26.3-27.5) CLD and 28.6 (28.3-29.0) non-CLD] [weeks [95% confidence interval (CI)]], as was the birth weight [973 (877.4-1068.8) CLD versus 1221 (1135.0-1307.0) non-CLD] [g (CI)]. CLD infants compared to non-CLD infants were significantly more likely to have been: given surfactant, ventilated and on oxygen at 28 days and 36 weeks. These neonates were also more likely to have: been discharged from the neonatal unit on oxygen, exhibit a history of PDA or sepsis and to have a current paediatrician. However, despite these differences, there was no significant difference in the proportion of asthma or atopic disease between the two groups., Conclusions: The RESPOS could not demonstrate respiratory and/or atopy differences between the CLD and the non-CLD groups at primary school age.

Aims: We examined potential risk of serotonin toxicity in Australian veterans by quantifying the concomitant use of serotonergic medicine combinations from claims data collected by the Department of Veterans' Affairs (DVA)., Methods: This was a retrospective cohort study of 273 228 Australian veterans, war widows, widowers and dependents aged >or=55 years and holding full treatment entitlement for the period July 2000 to June 2004 or until death. The main outcome measure was potential concomitant use, estimated as the number of cohort members with an overlap in days of supply for serotonergic medicine combinations over the 4 year period for all medicine combinations and potentially life threatening combinations., Results: From July 2000 to June 2004, 115 969 (42%) cohort members were dispensed at least one serotonergic medicine. 20 658 (8%) had at least one episode of potential concomitant use. We identified 1811 (0.7%) cohort members with at least one overlapping period of potentially life-threatening serotonergic medicine combinations, 937 of whom had the combinations dispensed within the recommended washout period. Three hundred and seventeen of these individuals were dispensed potentially life-threatening medicine combinations on the same day. The most common combinations were moclobemide with a selective serotonin reuptake inhibitor or tramadol., Conclusions: The individuals potentially at risk of mild to moderate serotonin toxicity were considerable and potentially life threatening combinations were not infrequent. While we were unable to determine how many individuals experienced serotonin toxicity this study indicates, for the first time, the potential size of the problem in a subgroup of elderly Australians. Clinicians and patients need to be vigilant regarding inadvertent concomitant use, especially that of moclobemide with a selective serotonin reuptake inhibitor or tramadol.

Purpose: Identification of biologically and clinically distinct breast cancer subtypes could improve prognostic assessment of primary tumors. The characteristics of "molecular" breast cancer subtypes suggest that routinely assessed histopathologic features in combination with limited biomarkers may provide an informative classification for routine use., Experimental Design: Hierarchical cluster analysis based on components of histopathologic grade (tubule formation, nuclear pleomorphism, and mitotic score), expression of ER, cytokeratin 5/6, and HER2 amplification identified four breast cancer subgroups in a cohort of 270 cases. Cluster subgroup membership was compared with observed and Adjuvant! Online predicted 10-year survival. Survival characteristics were confirmed in an independent cohort of 300 cases assigned to cluster subgroups using a decision tree model., Results: Four distinct breast cancer cluster subgroups (A-D) were identified that were analogous to molecular tumor types and showed a significant association with survival in both the original and validation cohorts (P < 0.001). There was a striking difference between survival for patients in cluster subgroups A and B with ER(+) breast cancer (P < 0.001). Outcome for all tumor types was well estimated by Adjuvant! Online, with the exception of cluster B ER(+) cancers where Adjuvant! Online was too optimistic., Conclusions: Breast cancer subclassification based on readily accessible pathologic features could improve prognostic assessment of ER(+) breast cancer.

Objective and Background: Reattendance rates at hospitals and emergency departments (ED) can provide a valuable marker of the quality and effectiveness of clinical care. Linked hospital and ED data from New South Wales and Victoria, Australia, were used to examine reattendances for asthma., Methods: Hospital and ED data were linked to identify individuals who reattended hospital or ED for asthma within 28 days of an initial attendance. The sociodemographic characteristics that predicted reattendance were examined using logistic regression., Results: There were 139,043 attendances for asthma between July 2000 and June 2003 attributed to 95,042 people. Overall, 7.1% of people reattended for asthma within 28 days. There was a significantly higher risk of reattendance among females (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.03-1.14), people who lived in areas of greater socioeconomic disadvantage (OR 1.20, 95% CI 1.12-1.29) and Indigenous people (OR 1.15, 95% CI 1.00-1.32). Reattendance rates differed among age groups (P < 0.001), with the lowest rate being in 5- to 14-year-olds., Conclusion: The availability of linked hospital and ED data has provided a rare opportunity to investigate predictors of reattendance for asthma. Surveillance of trends in reattendances for asthma can be used to monitor the effectiveness of interventions to improve asthma control across the continuum of care, particularly in higher-risk groups such as Indigenous people, young children and those with greater socioeconomic disadvantage.

Objective: To investigate whether the variables in the National Hospital Morbidity Database (NHMD) provide sufficient information to validly link hospital admission records for the same person so that persons admitted and re-admissions for a specified disease can be enumerated., Methods: Records of hospital admissions where asthma was the principal diagnosis were extracted from the New South Wales Inpatient Statistics Collection for the period July 2000 to June 2003 and linked using several strategies. The optimal' strategy applied probabilistic record linkage, using many demographic and administrative variables. A range of restricted strategies, using only those variables that were available with the NHMD (sex, date of birth, and either postcode or statistical local area of residence) and linking them deterministically, were evaluated and their validity for quantifying readmission for asthma within 28 days was assessed relative to the optimal strategy., Results: The optimal and restricted linkage strategies obtained similar estimates of readmissions. Approximately 95% of readmissions within 28 days identified using the optimal strategy were also identified using the restricted strategies., Conclusions: Linking hospital records where asthma was the principal diagnosis using only those variables available in the NHMD enabled reliable identification of hospital readmissions tor asthma., Implications: This methodology may have useful applications for monitoring the rate of readmissions for asthma and other chronic diseases nationally.

Background: Human herpesvirus 8 (HHV-8) is a common sexually transmitted agent among homosexual men, but there are few Australian data. We aimed to describe the prevalence and risk factors for seropositivity to HHV-8 in Australian homosexual men., Methods: We conducted a prospective cohort study of 179 homosexual men in Sydney Australia in 1992-1998. Detailed data on sexual behaviour was collected annually, and HHV-8 status was determined at the end of the study by an algorithm based on results of an immunofluorescence assay and an enzyme-linked immunoassay to the K8.1 protein of HHV-8. HHV-8 DNA was detected in buffy coats using a nested qualitative PCR., Results: Data on sexual behaviour in at least three interviews and HHV-8 status were available in 174 (97%) of 179 men who agreed to participate. Of these, 31 (18%) were HHV-8 seropositive, and HHV-8 DNA was detected in 5 (16%) of these. The prevalence of HHV-8 infection was much higher in HIV positive (52%) than HIV negative (11%) men (OR 8.60, 95% CI 3.55-20.86). HHV-8 infection was related to more frequent reporting of unprotected receptive anal sex (OR for most frequent versus least frequent category 3.03, 95% CI 1.01-9.03, P trend 0.02), insertive oro-anal sex (OR for most frequent v. least frequent category 3.02, 95% CI 1.15-7.93, P trend 0.02) and receptive oro-anal sex (OR for most frequent v. least frequent category 3.09, 95% CI 1.11-8.60, P trend 0.05) with casual partners., Conclusions: These data are consistent with sexual transmission of HHV-8, but the precise mode of HHV-8 transmission remains unclear. Studies to elucidate the precise mode of sexual transmission of HHV-8 need to focus on potential salivary transmission, and should collect data on the HHV-8 infection and excretion status of the sexual partner.

Objective: To determine if long-term improvement in HIV lipoatrophy can be attained by substitution of thymidine analogues zidovudine (ZDV) or stavudine (d4T) with abacavir (ABC)., Design: Long-term follow-up (104 weeks) of a randomized, open-label study., Setting: Seventeen ambulatory HIV clinics in Australia and London., Subjects: Patients with HIV lipodystrophy were randomized to switch from a thymidine analogue to ABC, while continuing all other antiretroviral therapy (ABC arm) (n = 42) or continue current therapy (ZDV/d4T arm) (n = 43)., Intervention: At week 24, all control patients could switch to ABC. Of the original 111 patients randomized, 85 had long-term follow-up data, with 77 having imaging data available at 104 weeks., Main Outcome Measure: The primary endpoint was time-weighted change in limb fat mass, measured by dual-energy X-ray absorptiometry (DEXA)., Results: At week 104, the mean increase in limb fat for the ABC and ZDV/d4T group was 1.26 +/- 2.02 kg and 0.49 +/- 1.38 kg, respectively. The time-weighted change for limb fat was significantly different between the two arms (0.43 kg; P = 0.008). On-treatment analysis demonstrated a trend for increased limb fat in patients in the ABC arm. Visceral fat accumulation, buffalo hump, self-assessed lipodystrophy or the lipodystrophy case definition score (LCDS) did not improve., Conclusions: In patients with moderate-to-severe lipodystrophy, significant improvements in subcutaneous fat continued over 104 weeks after switching from a thymidine analogue to ABC. Nevertheless, the lipodystrophy syndrome was still evident, indicating additional strategies need evaluating.

Objective: To investigate the association between oral health status and social, economic and demographic factors in community-dwelling older people in New South Wales (NSW)., Methods: Binary and multinomial logistic regression analyses were used to examine the associations between measures of oral health status (edentulous/dentate, and the frequency of toothache or mouth or denture problems in the previous 12 months) and demographic and socio-economic factors using data from the NSW Older People's Health Survey 1999., Results: After adjusting for other factors, being edentulous was associated with being older, having no private dental insurance, being female, leaving school at less than 15 years of age, not being financially comfortable, not being a homeowner, living in a rural area, and being unable to travel alone. Among both dentate and edentulous people, increasing age and being able to travel independently were associated with decreased reporting of toothache, mouth or denture problems; while not being financially comfortable was associated with increased reporting of toothache or mouth or denture problems. The frequency of mouth or denture problems was not found to be independently associated with having private dental insurance nor with holding a health concession card., Conclusions: Among older people in NSW, oral health is associated with a range of demographic and socio-economic factors. The results suggest that better oral health among older people is associated with a capacity to pay out-of-pocket dental expenses rather than with private dental insurance or having access to public-funded dental care.

Aim: The primary aim of the study was to compare the practice outcomes of doctors who graduated from a non-traditional, problem-based medical school (University of Newcastle) with those of graduates from a traditional programme (University of Sydney), matched randomly on the background characteristics of graduation year, age, gender, and rural primary and secondary school education. Our secondary aim was to differentiate admission from curricular influences by comparing the outcomes of Newcastle and Sydney graduates who entered medical school under similar admission criteria ('traditional academic' entry)., Design: Nested case-control analysis in a retrospective cohort study., Methods: A validated mail-out survey was distributed to all Newcastle and Sydney graduates registered to practise in the state of New South Wales, Australia., Outcome Measures: Current main occupation (clinician or other), clinical career choice (family medicine and psychiatry or other specialties), practice location (urban or rural) and employment sector (public or private)., Results: A total of 513 Newcastle respondents (68% of the original, eligible Newcastle sample) were each matched randomly with a Sydney respondent according to the four background characteristics. Medical school background was not related to main occupation; over 90% of all graduates were employed in clinician positions. A greater proportion of Newcastle than Sydney graduates were either training or qualified in family medicine or psychiatry rather than in other specialties. The school of graduation was not related to practice environment; fewer than 20% of all graduates were working in rural locations and around 25% were employed in the public sector. There were no differences in outcome between Newcastle and Sydney graduates who had entered medical school under similar academic criteria., Conclusion: Our study suggests that initial selection procedures of medical school candidates with particular background characteristics and attributes may influence practice outcomes. Further research is required to confirm these findings.