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Background: NHS England's 'Enhanced Health in Care Homes' specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches vary widely: challenges include frailty identification, multidisciplinary team (MDT) capability/capacity and how the process is structured and delivered., Aim: To determine whether a proactive healthcare model could improve healthcare outcomes for care home residents., Design and Setting: Quality improvement project involving 429 residents in 40 care homes in a non-randomised crossover cohort design. The headline outcome was 2-year survival., Method: All care home residents had healthcare coordinated by the PCN's Older Peoples' Hub. A daily MDT managed the urgent healthcare needs of residents. Proactive healthcare, comprising information technology-assisted comprehensive geriatric assessment (i-CGA) and advanced care planning (ACP), were completed by residents, with prioritisation based on clinical needs.Time-dependent Cox regression analysis was used with patients divided into two groups:Control group: received routine and urgent (reactive) care only.Intervention group: additional proactive i-CGA and ACP., Results: By 2 years, control group survival was 8.6% (n=108), compared with 48.1% in the intervention group (n=321), p<0.001. This represented a 39.6% absolute risk reduction in mortality, 70.2% relative risk reduction and the number needed to treat of 2.5, with little changes when adjusting for confounding variables., Conclusion: A PCN with an MDT-hub offering additional proactive care (with an i-CGA and ACP) in addition to routine and urgent/reactive care may improve the 2-year survival in older people compared with urgent/reactive care alone., Competing Interests: Competing interests: The IT-assisted Comprehensive Geriatric Assessment (i-CGA) is owned by Target Health Solutions (THS, a company that enhances primary care IT). DA and JB are directors in THS., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Frailty interventions such as Comprehensive Geriatric Assessment (CGA) can provide significant benefits for older adults living with frailty. However, incorporating such proactive interventions into primary care remains a challenge. We developed an IT-assisted CGA (i-CGA) process, which includes advance care planning (ACP). We assessed if, in older care home residents, particularly those with severe frailty, i-CGA could improve access to advance care planning discussions and reduce unplanned hospitalisations., Method: As a quality improvement project we progressively incorporated our i-CGA process into routine primary care for older care home residents, and used a quasi-experimental approach to assess its interim impact. Residents were assessed for frailty by General Practitioners. Proactive i-CGAs were completed, including consideration of traditional CGA domains, deprescribing and ACP discussions. Interim analysis was conducted at 1 year: documented completion, preferences and adherence to ACPs, unplanned hospital admissions, and mortality rates were compared for i-CGA and control (usual care) groups, 1-year post-i-CGA or post-frailty diagnosis respectively. Documented ACP preferences and place of death were compared using the Chi-Square Test. Unplanned hospital admissions and bed days were analysed using the Mann-Whitney U test. Survival was estimated using Kaplan-Meier survival curves., Results: At one year, the i-CGA group comprised 196 residents (severe frailty 111, 57%); the control group 100 (severe frailty 56, 56%). ACP was documented in 100% of the i-CGA group, vs. 72% of control group, p < 0.0001. 85% (94/111) of severely frail i-CGA residents preferred not to be hospitalised if they became acutely unwell. For those with severe frailty, mean unplanned admissions in the control (usual care) group increased from 0.87 (95% confidence interval ± 0.25) per person year alive to 2.05 ± 1.37, while in the i-CGA group they fell from 0.86 ± 0.24 to 0.68 ± 0.37, p = 0.22. Preferred place of death was largely adhered to in both groups, where documented. Of those with severe frailty, 55% (62/111) of the i-CGA group died, vs. 77% (43/56) of the control group, p = 0.0013., Conclusions: Proactive, community-based i-CGA can improve documentation of care home residents' ACP preferences, and may reduce unplanned hospital admissions. In severely frail residents, a mortality reduction was seen in those who received an i-CGA., (© 2024. The Author(s).)

Aim: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme., Methods and Results: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n = 3, range = 1-3) compared with non-carriers (median n = 9, range = 1-7) (P = 0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n = 10, range = 3-8) than non-carriers (median n = 5, range = 3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P = 1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging., Conclusion: Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background: older people living with frailty benefit from targeted interventions which improve health and independence. However, it has been challenging within primary care to systematically identify patients living with frailty., Methods: primary care IT was re-programmed to create a 'Pathfields High Risk Cohort' (PHRC, patients felt likely to have undiagnosed frailty) and invite clinicians to opportunistically assess and diagnose frailty. Results were compared with NHS England's current approach to frailty identification using Electronic Frailty Index (eFI) to see which approach had the highest diagnostic yield., Results: the Pathfields Tool identified 1,348 patients in PHRC group, of whom 951 (70.5%) were clinically assessed and diagnosed:eFI (moderate and severe) identified 683 patients of whom 598 (87.6%) were clinically assessed and diagnosed:Extrapolated data would estimate frailty prevalence at 22.5% (1,024/4,552) (5.5% severe, 8.8% moderate, and 8.1% mild) in the practice population aged 65+., Conclusions: the Pathfields Tool identified more patients with clinically confirmed previously undiagnosed frailty than eFI 'moderate and severe frailty' alone.Sub-segmenting frailty by residential status could significantly improve the population health management of older people., (© Crown copyright 2020.)

Immune checkpoint inhibitor blockade has vastly changed treatment paradigms and improved outcomes of many solid organ malignancies. The achievements of the last decade have transformed the outcomes of several tumour types, most notably metastatic melanoma. There are, however, still large numbers of patients who receive checkpoint inhibitor therapy and do not respond. In addition to potential lack of efficacy, checkpoint inhibitors also come with a unique and sometimes devastating side-effect profile. There exists a strong need for biomarkers to accurately predict response, improve treatment selection and avoid exposing patients to toxicity where there is minimal likelihood of response. There is a wide range of methodologies investigating predictive biomarkers in this space; in this review, we address the major putative biomarkers of interest. These include conventional serum tests such as lymphocyte indices and lactate dehydrogenase, and more novel research markers such as interleukin-6 and T receptor clonality. We discuss tumorous factors that may be of interest in certain tumour types, and finally gene expression profiling. Significant research continues into many of these potential predictive biomarkers in response to the emergent need to better select patients who will benefit from treatment., Competing Interests: Competing interests: Other disclosures are listed on the ICMJE form for Dr Desai., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Aim: To examine the cancer-specific outcomes for patients who experience immune-related adverse events requiring immunosuppression beyond corticosteroids., Methods: We performed a retrospective case series of patients between January 1, 2009 and April 1, 2018, across three metropolitan hospitals in Adelaide, South Australia. Eligible patients were identified from pharmacy records. Patients with a solid organ malignancy had discontinued checkpoint inhibitor therapy due to toxicity, and required immunosuppression in addition to corticosteroids to treat any immune-related adverse event., Results: From 3860 patient dispensation records of immunosuppressive medications, 19 eligible patients were identified. Eight received a CTLA-4 inhibitor, four a PD-1 inhibitor, five combination immunotherapy, and two remained blinded. Sixteen patients had melanoma and three had non-small cell lung cancer. Median time to treatment failure was 8.7 months, and median overall survival was 9.4 months. Of those evaluable, the objective response rate was 35%, while 53% had progressive disease. Four patients died due to complications of their irAE, while six died from progressive disease., Conclusion: Patients who received immunosuppression for checkpoint inhibitor therapy toxicity had variable outcomes. This in part reflects a heterogeneous population, and the evolution of irAE management over time. Several patients continued to derive a benefit after cessation of therapy despite the use of immunosuppressive medications; conversely, four died as a direct consequence of their irAE. Physicians should promptly introduce immunosuppressive therapy in patients not responding to corticosteroids to mitigate the risk of life-threatening adverse events, given that current evidence does not clearly demonstrate a detriment to cancer-specific outcomes., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: It is increasingly recognized that older adults with cancer represent a diverse cohort of patients and that other comorbidities may have an equal impact on survival and quality of life as any diagnosis of malignancy. Competing risk has consequently emerged as an important concept in the design and reporting of geriatric oncology trials., Methods: We performed a systematic review of phase II and III oncology trials for systemic therapy in older patients with solid organ malignancy from the year 2000 until April 30, 2017. Forty-one trials including 7864 patients were identified for evaluation., Results: Only 15 trials (36.6%) employed disease-related end points to account for death from other causes, and only one study used statistical analysis that addressed competing risk. Seventeen studies (41.5%) of trials included some assessment of comorbidity or frailty. Twenty-one trials (51.2%) included any assessment of quality of life., Conclusions: This review demonstrates clear areas for improvement for future studies and highlights the need for careful consideration of trial design, data collection, and appropriate statistical methodology for reporting of competing risks in geriatric oncology trials.

The extravasation of cytotoxic agents into subcutaneous tissue is a serious complication of chemotherapy. Unfortunately, if such extravasation occurs into the pleural space, limited data is available to guide appropriate management. We present the first report in the literature of video-assisted thoracoscopy combined with a topoisomerase II inhibitor and iron chelator, dexrazoxane, in the successful management of this complication., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

This chapter describes a novel way of carrying out image analysis, reconstruction and processing tasks using cloud based service provided on the Australian National eResearch Collaboration Tools and Resources (NeCTAR) infrastructure. The toolbox allows users free access to a wide range of useful blocks of functionalities (imaging functions) that can be connected together in workflows allowing creation of even more complex algorithms that can be re-run on different data sets, shared with others or additionally adjusted. The functions given are in the area of cellular imaging, advanced X-ray image analysis, computed tomography and 3D medical imaging and visualisation. The service is currently available on the website www.cloudimaging.net.au .

Osteoarthritis is a chronic disease with a major impact on quality of life for a large proportion of the population. It is a disease for which to date there has been no disease-modifying therapy identified. As a result of its physiological role in articular cartilage, glucosamine sulphate has been postulated as a treatment for osteoarthritis. Claims have included symptomatic relief and even reduction in the rate of disease progression. Despite promising in vitro studies, however, the role of glucosamine sulphate in the management of osteoarthritis remains unclear. Studies addressing this issue have generated a wide range of conclusions, and these are discussed here. Methodological issues need to be addressed in order to gauge whether there is true benefit. On current evidence, it would appear that the benefits of dietary supplementation with glucosamine sulphate are limited to mild symptomatic relief, while a disease-modifying agent for this disease remains elusive., (© 2012 The Authors. International Journal of Evidence-Based Healthcare © 2012 The Joanna Briggs Institute.)