Short waits, happy patients and expert care, moving basic musculoskeletal care from the emergency department to a physiotherapist-led diversion pathway.

OBJECTIVE: Patients with musculoskeletal conditions (MSKCs) are highly prevalent in ED. This project explores the impact of the pilot phase of a 'diversion pathway', which directed patients with MSKCs from the ED waiting room to an outpatient clinic led by advanced-scope physiotherapists. METHODS: A prospective intervention study comparing care outcomes between patients in the 'diversion pathway' with usual ED care. The characteristics of patients considered eligible and non-eligible are described. RESULTS: Between May and December 2022, 1099 patients were diverted. For diverted patients, mean length of stay (LOS) in ED was reduced by 110 (95% confidence interval [CI]: 99-120) min and 4 h rule compliance improved by 19.3% compared to usual ED care. There were fewer patients who 'did not wait' (DNW) with the diversion pathway. The diverted group was young (median age 22 years and 41% paediatric), mostly low urgency, self-referred and arrived by private transport with minor limb trauma. The diversion pathway triage process appropriately identified 182 patients ineligible for diversion. 96.7% of patients reported satisfaction with care received from the diversion pathway. There was no change in ED representation rates for diverted patients. CONCLUSIONS: A new pathway resulted in reduced LOS, reduced DNW, high patient satisfaction and more people being discharged within 4 h for diverted patients compared to usual ED care. The pathway increased ED capacity, improved key ED performance metrics and safely expedited care delivery for patients.

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

BACKGROUND AND AIM: People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. METHODS: We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. RESULTS: Among 99 687 women aged ≥ 50 years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. CONCLUSIONS: Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Association between unstable diabetes mellitus and risk of pancreatic cancer.

BACKGROUND: Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS: We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS: Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.

Post-Stroke Lateropulsion: Resolution and Function After Discharge From Inpatient Rehabilitation - A Cohort Study.

Purpose: A person with post-stroke lateropulsion pushes their body toward their hemiparetic side and/or resists accepting weight onto their nonparetic side. Research findings regarding long-term persistence of lateropulsion and its association with function are lacking. This study reports associations between lateropulsion severity (Four Point Pusher Score - 4PPS) and functional outcome (Functional Independence Measure - FIM) at three months after discharge. Methods: This prospective cohort study included 41 consecutive admissions to a stroke rehabilitation unit. Lateropulsion severity and FIM were measured at admission, discharge and three-month follow-up. Lateropulsion status at discharge, stroke laterality, ongoing physiotherapy after discharge, and demographic variables (age and sex) were tested for association with FIM change over the follow-up period. Results: Complete data were available for 38 participants. Among these, 17 (44.7%) showed lateropulsion (4PPS ≥ 1) on admission, 9 (23.7%) showed persistent lateropulsion on discharge, and 7 (18.4%) showed persistent lateropulsion at three month follow-up. Improved functional status (FIM score) was seen at follow-up in those discharged with lateropulsion who had right-sided lesions but not in those with left-sided lesions. Conclusions: Lateropulsion can continue to resolve after discharge from inpatient rehabilitation. Larger cohort studies are needed to further explore associations between persistent lateropulsion and long-term outcomes.

Objectif: une personne présentant une latéropulsion après un accident vasculaire cérébral (AVC) pousse son corps du côté hémiplégique ou résiste à soutenir son poids du côté non parétique. Peu de recherches portent sur la persistance à long terme de la latéropulsion et son association avec la fonction. La présente étude rend compte des associations entre la gravité de la latéropulsion (score de Pusher en quatre points ­ 4PPS) et les résultats fonctionnels (mesure d'autonomie fonctionnelle ­ MAF) trois mois après le congé. Méthodologie: cette étude de cohorte prospective incluait 41 admissions consécutives dans une unité de réadaptation après un AVC. La gravité de la latéropulsion et la MAF ont été mesurées à l'admission, au congé et au suivi trois mois plus tard. Les chercheurs ont vérifié l'état de la latéropulsion au congé, la latéralité des AVC, la poursuite de la physiothérapie après le congé et les variables démographiques (âge et sexe) pour déterminer leur association avec les changements à la MAF pendant la période de suivi. Résultats: les chercheurs ont obtenu des données complètes au sujet de 38 participants. De ce nombre, 17 (44,7 %) présentaient une latéropulsion (4PPS ≥ 1) à l'admission, neuf (23,7 %), une latéropulsion persistante au congé, et sept (18,4 %) une latéropulsion persistante au suivi de trois mois. Les chercheurs ont observé une amélioration de l'état fonctionnel (score de MAF) au suivi chez les personnes qui présentaient une latéropulsion au congé et qui avaient des lésions du côté droit, mais pas chez celles dont les lésions se situaient du côté gauche. Conclusions: la latéropulsion peut continuer de s'atténuer après le congé de la réadaptation hospitalière. Il faudra tenir des vastes études de cohorte pour explorer davantage les associations entre la latéropulsion persistante et les résultats cliniques à long terme.

Association between antihypertensive medicine use and risk of ovarian cancer in women aged 50 years and older.

BACKGROUND: Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. METHODS: Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. RESULTS: We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). CONCLUSION: Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.

Accuracy of the Australian National Sub-Acute and Non-Acute Patient Classification in predicting rehabilitation length of stay for stroke survivors who are ≥65 years of age and have lateropulsion.

BACKGROUND: Lateropulsion is a common impairment after stroke. Regardless of stroke severity, functional recovery is slower in people with lateropulsion, resulting in requirement for longer rehabilitation duration. In Australia, inpatient rehabilitation funding is determined via the Australian National Sub-Acute and Non-Acute Patient Classification (AN-SNAP). AN-SNAP class is determined using age, diagnosis, weighted Functional Independence Measure (FIM) motor score, and FIM cognitive score. OBJECTIVES: To explore accuracy of the AN-SNAP to predict length of stay (LOS) for people with poststroke lateropulsion. METHODS: A retrospective database audit was undertaken. AN-SNAP predicted LOS for each participant was calculated based on 2019 calendar year national benchmarks. A multivariable linear regression model estimated mean differences in reported LOS and AN-SNAP predicted LOS after adjusting for lateropulsion severity (Four Point Pusher Score). A separate logistic regression model assessed whether FIM change during admission was associated with reported LOS exceeding AN-SNAP predicted LOS. RESULTS: Data were available from 1126 admissions. Reported LOS exceeding AN-SNAP predicted LOS was associated with greater lateropulsion severity on admission. Where AN-SNAP predicted LOS was longer, those with no lateropulsion on admission showed shorter reported than predicted LOS. Greater improvement in FIM during rehabilitation was associated with increased odds of reported LOS exceeding AN-SNAP predicted LOS (OR 1.02, 95%CI 1.01-1.03, p < .001). CONCLUSIONS: Inclusion of a measure of poststroke lateropulsion in the AN-SNAP classification model would result in more accurate LOS predictions to inform funding. Costs of longer rehabilitation LOS may be countered by optimized long-term physical function, reducing requirement for ongoing care.

Perioperative Beta-Blocker Supply and Survival in Women With Epithelial Ovarian Cancer and a History of Cardiovascular Conditions.

PURPOSE: Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study. MATERIALS AND METHODS: Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects. RESULTS: Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery. CONCLUSION: Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.

The association between diabetes mellitus of different durations and risk of pancreatic cancer: an Australian national data-linkage study in women.

AIMS: The bidirectional association between diabetes mellitus (DM) and pancreatic cancer (PC) is established; however, the strength of association between duration of DM and risk of PC needs further investigation. METHODS: We conducted a case-control study nested within a population-based cohort of Australian women established using record linkage. Women diagnosed with PC from July 2007 to December 2013, were matched to five controls based on age and state of residence. DM was defined according to prescription of anti-diabetic medication from administrative prescription data. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for area-level socioeconomic status, rurality of residence, weighted comorbidity score, and predicted probability of obesity. RESULTS: The analyses included 7,267 cases and 35,978 controls. The mean age at the time of DM diagnosis was 71 years whereas the mean age at the time of diagnosis of PC was 76 years. A history of DM of any duration was associated with a 2-fold increase in risk of PC (OR=2.12; 95%CI:1.96-2.29) compared to having no history of DM. The risk decreased with increasing duration of DM. The highest risk was in those who had recent-onset DM (OR=8.08; 95%CI:6.88-9.50 for <12 months of DM), but the risk remained elevated with ≥5 years of DM (OR=1.40; 95%CI:1.27-1.55). CONCLUSION: The markedly increased risk of PC in those with recent-onset DM emphasises the need for further research to distinguish patients for whom new-onset DM is a manifestation of PC from those with type-2 DM. The elevated risk associated with long-standing DM suggests that preventing DM may contribute to a reduction in the incidence of PC.

Brain cancer patients' levels of distress and supportive care needs over time.

PURPOSE: This study aimed to describe patient self-reported distress over time and how this was associated with wellbeing, and supportive care needs over a 6-month period from commencing chemoradiotherapy for high grade glioma (HGG). METHODS: In this prospective cohort study, participants completed surveys at three time points: before chemoradiotherapy, at 3 and 6 months. These included Distress Thermometer, Functional Assessment of Cancer/Brain Cancer Treatment-general (Fact-G/FACT-BR), Supportive Care Needs Scale (SF-34) and Brain Tumour Specific subscale. Patient survival time was also collected. Group-based trajectory modelling was performed. Multinominal logistic regression assessed variables associated with different distress trajectory groups. RESULTS: One hundred and sixteen participants completed assessments at baseline, 89 participants at 3 and 64 at 6 months. Four distress trajectory groups were identified; consistent low distress (18%), low to high distress (38%), high-to low distress (24%) and consistent high distress (19%). Younger participants tended to report decreased distress over time, whereas older participants reported consistently high distress. High distress trajectory participants had less education, lower physical wellbeing, more unmet needs, but higher functional wellbeing compared to the low to high distress trajectory. The number of unmet needs paralleled the patterns of distress over time. The highest unmet needs in people with HGG and high distress were disease specific changes in mental ability and physical side effects. CONCLUSION: This study demonstrates people with HGG experience ongoing distress and highlights a need for continuous distress and unmet needs screening and referrals.

Nitrogen-based Bisphosphonate Use and Ovarian Cancer Risk in Women Aged 50 Years and Older.

BACKGROUND: There are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype. METHODS: We conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia's universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes. CONCLUSION: Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.

Post-stroke lateropulsion and rehabilitation outcomes: a retrospective analysis.

PURPOSE: A person with post-stroke lateropulsion actively pushes themselves toward their hemiplegic side, or resists moving onto their non-hemiplegic side. This study aimed to determine the association of lateropulsion severity with: • Change in function (Functional Independence Measure - FIM) and lateropulsion severity (Four-Point Pusher Score - 4PPS) during inpatient rehabilitation; • Inpatient rehabilitation length of stay (LOS); • Discharge destination from inpatient rehabilitation. METHODS: Retrospective data for 1,087 participants (aged ≥65 years) admitted to a stroke rehabilitation unit (2005-2018) were analysed using multivariable regression models. RESULTS: Complete resolution of lateropulsion was seen in 69.4% of those with mild lateropulsion on admission (n = 160), 49.3% of those with moderate lateropulsion (n = 142), and 18.8% of those with severe lateropulsion (n = 181). Average FIM change was lower in those with severe lateropulsion on admission than those with no lateropulsion (p < 0.001). Higher admission 4PPS was associated with reduced FIM efficiency (p < 0.001), longer LOS (p < 0.001), (adjusted mean LOS: 35.6 days for those with severe lateropulsion versus 27.0 days for those without), and reduced likelihood of discharge home (p < 0.001). CONCLUSION: Post-stroke lateropulsion is associated with reduced functional improvement and likelihood of discharge home. However, given a longer rehabilitation duration, most stroke survivors with moderate to severe lateropulsion can achieve important functional improvement.Implications for RehabilitationWhile people with post-stroke lateropulsion can be difficult to treat and require more resources than those without lateropulsion, the majority of those affected, even in severe cases, can make meaningful recovery with appropriate rehabilitation.Although those with moderate to severe post-stroke lateropulsion may have poorer outcomes (longer LOS and reduced likelihood of discharge home) it is still important to advocate for access to rehabilitation for this patient group to give them the opportunity for optimal functional recovery.

Prescribing tailored home exercise program to older adults in the community using a tailored self-modeled video: A pre-post study.

Background: Community rehabilitation for older people after hospital discharge is necessary to regain functional ability and independence. However, poor adherence to exercise programs continues to hinder achieving positive health outcomes in older people. This study aimed to evaluate the effectiveness of prescribing a tailored video self-modeled DVD-HEP for 6 weeks, on functional mobility, physical activity, exercise self-efficacy, and health-related quality of life, in a sample of frail older adults. Materials and methods: A pre- and post-test intervention study design was conducted, with each participant acting as their own control. A convergent, parallel, mixed-methods approach involving quantitative, and qualitative data collection was used. Participants received an individualized assessment at baseline and subsequently were provided with a 30-min tailored 6-week self-modeled DVD-HEP that showed the physiotherapist instructing the participant. The physiotherapist phoned participants fortnightly to encourage engagement in the program and explore responses to it. Outcomes evaluated included functional mobility, balance, gait speed, and exercise self-efficacy. Results: Participants (n = 15) showed clinically meaningful improvements at follow-up compared to baseline in functional mobility (TUGMCID = 3.4-3.5 s, 3-MWTMCID = 0.1-0.2 m/s) and gait speed (3-MWTMCID = 0.1-0.2 m/s). There were also significant improvements in balance and self-efficacy for exercise and a 2.5- and a 1.3-fold increase in moderate and light physical activity participation at follow-up compared to baseline. The deductive themes were: (i) Enjoyment, self-efficacy, and wellbeing; (ii) Achieving life goals; (iii) Background music as a motivator to adherence; and (iv) Enhanced motor performance and learning: Task goal mastery, multimodal feedback, autonomy to self-regulate learning. The new inductive theme was (v) Preference for in-person support for exercise. Conclusion: Future studies are warranted to compare a tailored self-modeled video HEP to face-to-face programs and other digital health modalities to evaluate older adults' adherence levels and functional improvement.

Pretreatment With Mifepristone Compared With Misoprostol Alone for Delivery After Fetal Death Between 14 and 28 Weeks of Gestation: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of pretreatment with mifepristone before misoprostol, compared with misoprostol alone, for termination of pregnancy after a fetal death in the second trimester. METHODS: This prospective, double blind, placebo-controlled trial randomized women requiring a termination of pregnancy after fetal death between 14 and 28 weeks of gestation to placebo or 200 mg mifepristone orally 24-48 hours before the termination of pregnancy with misoprostol (400 micrograms every 6 hours vaginally for women at 24 weeks of gestation or less, and 200 micrograms every 4 hours vaginally for women at 24 weeks of gestation or more). Based on a median labor with misoprostol alone in the second trimester of 13 hours, a sample size of 116 women per group was planned to compare the primary outcome of time from administration of misoprostol to delivery. The trial was ceased after 66 women were enrolled secondary to prolonged time to achieve recruitment. RESULTS: From April 2013 to November 2016, 66 women were randomized (34 to placebo and 32 to mifepristone). There were no differences in the characteristics between the two groups. The median time for the primary outcome of administration of misoprostol to delivery in the placebo group was 10.5 hours, compared with 6.8 hours in the treatment group (hazard ratio 2.41 95% CI 1.39-4.17, P=.002). Women in the placebo group required more doses of misoprostol (3.4 vs 2.1, P=.002) and more misoprostol overall (1,181.8 micrograms, vs 767.7 micrograms, P=.003). There was no difference in maternal complications between the two groups. Women in the mifepristone group reported improved perception of the procedure. CONCLUSION: The sequential use of mifepristone and misoprostol for the termination of pregnancy after fetal deaths between 14 and 28 weeks of gestation reduces the time to delivery, compared with the use of misoprostol alone, with no worsening of maternal complications. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612000884808.

Starting a new anti-seizure medication in drug-resistant epilepsy: Add-on or substitute?

OBJECTIVES: Randomized studies in drug-resistant epilepsy (DRE) typically involve addition of a new anti-seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach. METHODS: Longitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time-to-event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution. RESULTS: A total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow-up was 3.2 years. Substitution was more likely if the new ASM was enzyme-inducing or in patients with a greater number of concurrent ASMs. ASM add-on was more likely if a γ-aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add-on and substitution groups. No difference between the add-on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months. SIGNIFICANCE: Adding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics.

Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) Resistance Mutation in Pre-treatment Non-small Cell Lung Carcinomas Harboring Activating EGFR Mutations and Correlation with Clinical Outcomes.

Increasing evidence points to the presence of low-level de novo T790M mutations in patients with non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations. We utilized digital PCR (dPCR), a highly sensitive gene mutation detection method, to detect pre-treatment T790M mutations in NSCLC tumor samples and correlated the T790M status with clinical features and patient outcomes. DNA extracted from pre-treatment NSCLC tumor tissue with known activating EGFR mutations, diagnosed between October 2010 and May 2017 at PathWest laboratory, was used to perform targeted dPCR for quantitative detection of T790M mutations. T790M was detected in 42 of 109 pre-treatment samples (38.5%). Median variant allele frequency was 0.14% (range 0.02-28.5%). Overall response rate to first generation EGFR tyrosine kinase inhibitors (TKI) was 67% regardless of T790M status. The median progression free survival was 10.7 (IQR 5.6-19.9) versus 6.7 (IQR 3.5-20.8) months in T790M negative and positive patients respectively. T790M positivity correlated with increased rate of early disease progression. It also correlated with increased mortality (HR 3.1 95%CI 1.2-8.1, p = 0.022) in patients who did not respond to TKI treatment. We detected a significant rate of low-level pre-treatment T790M mutations in NSCLC using highly sensitive dPCR. Low-level pre-treatment T790M did not impact treatment response rate or overall survival, but was associated with increased rate of early progression on TKI therapy.

Objective quantification of burn scar stiffness using shear-wave elastography: Initial evidence of validity.

Shear-wave elastography (SWE) is an ultrasound based technology that can provide reliable measurements (velocity) of scar stiffness. The aim of this research was to evaluate the concurrent validity of using both the measured velocity and the calculated difference in velocity between scars and matched controls, in addition to evaluating potential patient factors that may influence the interpretation of the measurements. METHODS: A cross-sectional study of 32 participants, with 48 burn scars and 48 matched contralateral control sites were evaluated with SWE, the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS) tactile sub-scores. RESULTS: Spearman's rho demonstrated high correlations (r > 0.7) between the measured scar velocity and both the POSAS and VSS pliability sub-scores, whereas moderate correlations (r > 0.6) were found with the calculated difference in velocity. Regression analysis indicated that the association of increased velocity in scars, varied by length of time after burn injury and gender. Body location and Fitzpatrick skin type also demonstrated significant associations with velocity, whereas age did not. CONCLUSION: SWE shows potential as a novel tool to quantify burn scar stiffness, however patient factors need to be considered when interpreting results. Further research is recommended on a larger variety of scars to support the findings.

A Novel, Reliable Protocol to Objectively Assess Scar Stiffness Using Shear Wave Elastography.

The aim of this research was to investigate the use of shear wave elastography as a novel tool to quantify and visualize scar stiffness after a burn. Increased scar stiffness is indicative of pathologic scarring which is associated with persistent pain, chronic itch and restricted range of movement. Fifty-five participants with a total of 96 scars and 69 contralateral normal skin sites were evaluated. A unique protocol was developed to enable imaging of the raised and uneven burn scars. Intra-rater and inter-rater reliability was excellent (intra-class correlation coefficient >0.97), and test-retest reliability was good (intra-class correlation coefficient >0.85). Shear wave elastography was able to differentiate between normal skin, pathologic scars and non-pathologic scars, with preliminary cutoff values identified. Significant correlations were found between shear wave velocity and subjective clinical scar assessment (r = 0.66). Shear wave elastography was able to provide unique information associated with pathologic scarring and shows promise as a clinical assessment and research tool.

Increased risk of blood transfusion in patients with diabetes mellitus sustaining non-major burn injury.

BACKGROUND: Due to the increased mortality and morbidity associated with blood transfusion, identifying modifiable predictors of transfusion are vital to prevent or minimise blood use. We hypothesised that burn patients with diabetes mellitus were more likely to be prescribed a transfusion. These patients tend to have increased age, number of comorbidities, infection risk and need for surgery which are all factors reported previously to be associated with blood use. OBJECTIVE: To determine whether patients with diabetes mellitus who have sustained a burn ≤20% total body surface area (TBSA) are at higher risk of receiving red blood cell transfusion compared to those without diabetes mellitus. METHOD: This was a retrospective cohort study including patients admitted to the major Burns Unit in Western Australia for management of a burn injury. Only the first hospital admission between May 2008 to February 2017 were included. RESULTS: Among 2101 patients with burn injuries ≤20% TBSA, 48 (2.3%) received packed red blood cells and 169 (8.0%) had diabetes. There were 13 (7.7%) diabetic patients that were transfused versus 35 (1.8%) non-diabetic patients. Patients with diabetes were 5.2 (p = 0.034) times more likely to receive packed red blood cells after adjusting for percentage TBSA, haemoglobin at admission or prior to transfusion, number of surgeries, total comorbid burden and incidence of infection. As percentage TBSA increases, the probability of packed red blood cell transfusion increases at a higher rate in DM patients. CONCLUSIONS: This study showed that diabetic patients with burn injuries ≤20% TBSA have a higher probability of receiving packed red blood cell transfusion compared to patients without diabetes. This effect was compounded in burns with higher percentage TBSA.

RANZCOG Fellows' adherence to guidelines following cytological prediction of cervical adenocarcinoma-in-situ: Cause for concern?

BACKGROUND: For Australian women with screen-detected adenocarcinoma-in-situ (AIS), an excisional biopsy is mandatory for further assessment, treatment, and to exclude the presence of cervical adenocarcinoma. The only exclusion to this rule is if the woman has a clinically evident invasive cervical malignancy. Excisional treatments should be tailored according to a patient's age and future obstetric needs. To date, practitioner compliance with this recommendation has not been investigated. AIMS: To investigate clinical management for patients with a cytological test result predicting AIS. Secondary aims were to report the most severe histological findings of excisional biopsy specimens following cytological prediction of AIS and investigate treatment outcomes for conservatively managed patients with biopsy-confirmed AIS. MATERIALS AND METHODS: A retrospective, population-based cohort study was conducted. Cases were ascertained from the Tasmanian and Western Australia Cervical Screening Registries. Cytology and histology results for women with an index cervical smear reporting AIS from 2001 to 2012 were reviewed. RESULTS: Three hundred and twenty-one women (age range 18-69 years) had an index smear reporting AIS. Cervical cancer was diagnosed in 62 (19.3%) patients within the study cohort. Twenty-one of 321 patients (6.7%) were not initially managed according to the 2005 NHMRC Guidelines for the management of asymptomatic women with screen-detected abnormalities, including two women diagnosed with an occult cancer following a total hysterectomy. CONCLUSIONS: A minority of women were not managed in accordance with guidelines. This is of concern given that nearly one in five women with a smear predicting AIS had a final diagnosis of cervical cancer.