Improving regional lung cancer optimal care pathway compliance through a rapid-access respiratory clinic.

BACKGROUND: Lung cancer is the leading cause of cancer-related morbidity and mortality in Australia and delays in diagnosis and management increase the potential for disease progression. Incidence and mortality from lung cancer in our region, Gippsland, are higher than the national average, yet there is no known standard referral pathway for diagnosis in the region. AIM: To identify the current standard of care for lung cancer diagnosis and the impact a rapid access clinic, led by a respiratory physician, has on optimal care pathway (OCP) compliance. METHODS: A retrospective audit of patients with lung cancer managed through our regional hospital between January and December 2018 (Standard Care group), and a prospective audit of a new rapid access, respiratory-physician led, lung lesion assessment clinic over the same period, were conducted. The primary outcomes were compliance with the OCP target for time from initial computed tomography scan identification of a lung lesion to tissue diagnosis and treatment commencement (target 42 days) when malignancy was confirmed. RESULTS: There were 25 cases audited in the Standard Care group and 21 cases seen through the Rapid Access Clinic. The Standard Care group met the target for treatment commencement in 33.3% of cases whereas the Rapid Access Clinic group achieved this in 77%. CONCLUSIONS: Our project highlights the disjointed and delayed lung cancer care in our region and the improvements a dedicated rapid access clinic can have on diagnosis and treatment commencement timeframes.

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.

Grass-Endophyte Interactions and Their Associated Alkaloids as a Potential Management Strategy for Plant Parasitic Nematodes.

Claviceptaceous endophytic fungi in the genus Epichloë mostly form a symbiotic relationship with cool-season grasses. Epichloë spp. are capable of producing bioactive alkaloids such as peramines, lolines, ergot alkaloids, and indole-diterpenes, which protect the host plant from herbivory by animals, insects, and nematodes. The host also benefits from enhanced tolerance to abiotic stresses, such as salt, drought, waterlogging, cold, heavy metals, and low nitrogen stress. The bioactive alkaloids produced can have both direct and indirect effects towards plant parasitic nematodes. Direct interaction with nematodes' motile stages can cause paralysis (nematostatic effect) or death (nematicidal effect). Indirectly, the metabolites may induce host immunity which inhibits feeding and subsequent nematode development. This review highlights the different mechanisms through which this interaction and the metabolites produced have been explored in the suppression of plant parasitic nematodes and also how the specific interactions between different grass genotypes and endophyte strains result in variable suppression of different nematode species. An understanding of the different grass-endophyte interactions and their successes and failures in suppressing various nematode species is essential to enable the proper selection of grass-endophyte combinations to identify the alkaloids produced, concentrations required, and determine which nematodes are sensitive to which specific alkaloids.

Supporting international medical graduates in rural Australia: a mixed methods evaluation.

INTRODUCTION: In Australia, international medical graduates (IMGs) make a substantial contribution to rural medical workforces. They often face significant communication, language, professional and cultural barriers, in addition to the other challenges of rural clinical practice. The Gippsland Inspiring Professional Standards among International Experts (GIPSIE) program was designed to provide educational support to IMGs across a large geographical region using innovative educational methods to ultimately build capacity in the provision of rural medical education. GIPSIE offered 5 sessions over 3 months. Simulation-based training was a prominent theme and addressed clinical knowledge, attitudes and skills and included a range of activities (eg procedural skills training with benchtop models, management of the acutely ill patient with SimMan, patient assessment skills with simulated patients). Diverse clinical communication skills were explored (eg teamwork, handover, telephone, critical information). Audiovisual review of performance was enabled through the use of iPod nano devices. GIPSIE was underpinned by a website offering diverse learning resources. Content experts were invited to lead sessions that integrated knowledge and skills reflecting local practice. METHODS: IMGs were recruited from hospitals (n = 15) and general practices (n = 2) across the region. It was aimed to evaluate the impact of GIPSIE on the clinical practice of IMG participants. Evaluation measures included pre- and post-program 15 item multisource feedback (MSF), post-program questionnaires and, in order to address retention, telephone interviews exploring participants' responses 3 months after the program finished. RESULTS: Fifteen participants completed GIPSIE and rated the program highly, especially the simulation-based activities with feedback and later audiovisual review on iPods and the GIPSIE website. Suggestions were made to improve several aspects of the program. Participants reported increased knowledge, skills and professionalism after the program. Although overall MSF scores showed no statistically significant changes, there were positive directional changes for the items 'technical skills appropriate to current practice', 'willingness and effectiveness when teaching/training colleagues' and 'communication with carers and family'. These developments were also supported in free-text comments. Learning was reported to be sustained 3 months after the program. CONCLUSIONS: GIPSIE was highly valued by participants who reported improvements in clinical knowledge and skills. A range of professional issues were raised and addressed. GIPSIE seemed to provide a platform for further development. Although new to many participants, simulation was embraced as an educational method. The relationship between regional clinicians and the medical school was pivotal to success. A feature of the study was tracking improvements in clinical practice as a consequence of participating in the GIPSIE program. Future work needs to focus on further promoting the transfer of learning to the workplace. However the sustainability of these programs requires significant commitment.

A new method to validate and compare varietal resistance and yield tolerance of sugar beet (Beta vulgaris) against the beet cyst nematode, Heterodera schachtii Schmidt.

BACKGROUND: Beet cyst nematode, Heterodera schachtii Schmidt is a global threat to sugar beet crops, and is found in every major sugar beet growing region. Annual losses due to this nematode can be severe, being estimated at €90 m in Europe alone in the 1990s. Fortunately tolerant, resistant and partially resistant varieties have since been introduced which help to limit yield loss and are now widely being deployed in infested fields. However, understanding yield performance of these varieties has been difficult, especially when variety testing programmes usually require uninfested fields. RESULTS: For the first time, and in a standardised manner, we can now assess simultaneously the resistance of different varieties to BCN and their actual yield tolerance, by comparing them to varieties grown in uninfested micro-plots alongside those which are infested. This method provides new insights on variety yield performance and nematode reproduction over an entire growing season. In addition, the investigations are also been able to detect significant physiological differences in the development and growth of the tolerant varieties' canopies and leaf chlorophyll levels. CONCLUSIONS: Our findings are of direct benefit to sugar beet growers challenged by BCN. The standardised testing provides new information on predicted variety performance. We found that these tests are justified, as not all tolerant varieties respond in the same manner to nematode infestation. Therefore, these assessments will become a vital part of variety testing for sugar beet growers, allowing for tailored deployment of variety types and more informed decision making on-farm, helping to maximise yields whilst minimising nematode damage. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Evaluating resistant brassica trap crops to manage Heterodera schachtii (Schmidt) infestations in eastern England.

BACKGROUND: The beet cyst nematode (BCN), Heterodera schachtii Schmidt, is a plant parasitic nematode that causes severe yield losses in sugar beet. Resistant brassicas (radish and mustard) have been bred to be planted after harvest of the main crop, for example a cereal, and encourage BCN juvenile hatching. The resistant plants stimulate juvenile hatching but are not suitable hosts. Juveniles are unable to complete their lifecycle and thus populations are lowered. This research aimed to investigate the effectiveness of a range of brassicas in terms of BCN control when grown in infested fields in eastern England. RESULTS: Experiments used four different radish cultivars, which differed in their resistance to BCN, and one resistant mustard variety. Field experiments were sown in early September in 2016 and 2017. Significant reductions in BCN populations were found only following resistant mustard and the radish with the greatest resistance level. CONCLUSIONS: Further research is needed to understand how best to utilize brassicas and whether they are economically viable when alternative management options for BCN are available. Time of planting may be crucial to fully achieve their BCN-reducing potential. © 2018 Society of Chemical Industry.

SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia.

BACKGROUND: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS: The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS: In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

BACKGROUND: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Implementation of a multi-level evaluation strategy: a case study on a program for international medical graduates.

Evaluation of educational interventions is often focused on immediate and/or short-term metrics associated with knowledge and/or skills acquisition. We developed an educational intervention to support international medical graduates working in rural Victoria. We wanted an evaluation strategy that included participants' reactions and considered transfer of learning to the workplace and retention of learning. However, with participants in distributed locations and limited program resources, this was likely to prove challenging. Elsewhere, we have reported the outcomes of this evaluation. In this educational development report, we describe our evaluation strategy as a case study, its underpinning theoretical framework, the strategy, and its benefits and challenges. The strategy sought to address issues of program structure, process, and outcomes. We used a modified version of Kirkpatrick's model as a framework to map our evaluation of participants' experiences, acquisition of knowledge and skills, and their application in the workplace. The predominant benefit was that most of the evaluation instruments allowed for personalization of the program. The baseline instruments provided a broad view of participants' expectations, needs, and current perspective on their role. Immediate evaluation instruments allowed ongoing tailoring of the program to meet learning needs. Intermediate evaluations facilitated insight on the transfer of learning. The principal challenge related to the resource intensive nature of the evaluation strategy. A dedicated program administrator was required to manage data collection. Although resource-intensive, we recommend baseline, immediate, and intermediate data collection points, with multi-source feedback being especially illuminating. We believe our experiences may be valuable to faculty involved in program evaluations.

Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity.

Normal skeletal muscle development requires the proper orchestration of genetic programs by myogenic regulatory factors (MRFs). The actions of the MRF protein MyoD are enhanced by the transcriptional coactivators p300 and the p300/CBP-associated factor (PCAF). We previously described C2 skeletal myoblasts lacking expression of insulin-like growth factor-II (IGF-II) that underwent progressive apoptotic death when incubated in differentiation-promoting medium. Viability of these cells was sustained by addition of IGF analogs or unrelated peptide growth factors. We now show that p300 or PCAF maintains myoblast viability as effectively as added growth factors through mechanisms requiring the acetyltransferase activity of PCAF but not of p300. The actions of p300 to promote cell survival were not secondary to increased expression of known MyoD targets, as evidenced by results of gene microarray experiments, but rather appeared to be mediated by induction of other genes, including fibroblast growth factor-1 (FGF-1). Conditioned culture medium from cells expressing p300 increased myoblast viability, and this was blocked by pharmacological inhibition of FGF receptors. Our results define a role for p300 in promoting cell survival, which is independent of its acetyltransferase activity and acts at least in part through FGF-1.