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Objectives: Many oncology health professionals (HPs) report communicating with carers as complex; and receive limited carer-relevant training. We developed an online HP education program for supporting and managing carer involvement (eTRIO). We aimed to assess whether HPs' self-efficacy in carer communication, knowledge, and decision-making preferences improve following eTRIO. Satisfaction and implementation potential were assessed., Methods: This type 1 hybrid effectiveness-implementation study used a pre-post single arm intervention design. HPs completed baseline measures, the eTRIO online module, and measures at 1- and 12-weeks post-intervention. Measures included: self-efficacy in carer communication (13-items), applied knowledge (7-items), preference for carer involvement in decisions (1-item). Fifteen of participants completed feedback interviews which underwent thematic analysis. User analytics were collected and analysed., Results: Fifty-six HPs completed baseline measures, 42 completed post- and follow-up measures. At baseline mean self-efficacy score was 88. HPs showed a statistically significant increase in self-efficacy post-intervention (mean = 105.8, CI [12.99, 20.47]), maintained at 12-weeks (mean = 101.1, CI [8.00, 15.72]). There were no changes in knowledge or decision-making preferences. Program engagement and satisfaction were high, 86.7% participants rated eTRIO as very/extremely helpful., Conclusions and Practice Implications: eTRIO provided HPs with confidence to effectively engage with carers and manage complex situations such as family dominance. These gains are noteworthy, as conflict with families/carers contributes to HP burnout., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Breast reconstruction (BR) improves women's health-related quality of life (HRQOL) following mastectomy for breast cancer, yet factors contributing to improved HRQOL remain unclear. This study aimed to explore the overall impact of mastectomy with or without BR on participants' perceptions of HRQOL over time in a cohort of women with high-risk breast cancer; to examine differences in mean HRQOL scores between immediate BR, delayed BR and no BR groups; to assess the influence of patient characteristics potentially associated with HRQOL scores; and to determine the feasibility of long-term collection of patient-reported outcome measures in clinical settings., Methods: A prospective, longitudinal study of 100 women with high-risk breast cancer who underwent mastectomy with or without breast reconstruction and were likely to require post-mastectomy radiotherapy. Four validated patient-reported questionnaires, comprising 21 outcome measures relating to HRQOL, administered at baseline and up to 4 years post-mastectomy. Demographic, clinical and surgical data extracted from patient medical records., Results: Consistently significant declines in perceptions of future health and arm symptoms, consistently significant improvements in treatment side effects, breast symptoms and fatigue, as well as significant improvements, compared to baseline, in social functioning and financial difficulties at 48 months. No significant differences in mean HRQOL scores between women given a choice of reconstructive options., Conclusion: Similar trajectories of HRQOL scores were found in women with high-risk breast cancer who were offered a choice of BR. Informed choice may be an independent contributing factor in long-term maintenance of most HRQOL indicators at their pre-mastectomy levels., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: International guidelines recommend combining a CDK4/6 inhibitor and endocrine therapy (ET) as first line treatment for hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). Results from MONALEESA-2 demonstrate superior progression free survival (PFS) and overall survival (OS) with ribociclib (CDK4/6 inhibitor) and ET compared to ET alone. Real world outcomes have yet to be reported., Materials and Methods: KARMA is a non-interventional registry of Australian patients receiving first-line treatment with ribociclib and aromatase inhibitor (AI), obtained via a Medicine Access Program (MAP) for HR+, HER2- MBC. Outcomes were compared with the ribociclib/letrozole cohort in MONALEESA-2., Results: Data from 160 patients at 17 sites was analysed. Median follow-up is 36.5 months. Compared to MONALEESA-2, patients were numerically younger (54.3 vs. 62 years), with higher rates of bone-only metastases (31% vs. 21%). A total of 63 of 160 (39%) patients remain on treatment. A total of 56% of patients had at least 1 dose reduction, with neutropenia (68%) and abnormal liver enzymes (17%) the most common reasons. A total of 17 of 160 (11%) discontinued treatment due to toxicity, with no treatment related deaths. Median PFS was not reached (95% CI 29.9- NR), with PFS at 12 months and 18 months being 76% and 67% respectively versus 25.3 months, 73% and 63% in MONALEESA-2., Conclusion: The ribociclib and AI combination was well tolerated in this real-world setting. The KARMA registry cohort achieved a superior PFS (>36.5 months) to MONALEESA-2, potentially due to more favourable baseline disease characteristics. Less frequent assessment scheduling in this non trial setting may also contribute., Competing Interests: Disclosure Vanessa Wong has received speaker honoraria from Amgen and Janssen, and her affiliated institution is the recipient of research grant funding from Pierre-Fabre, Amgen, Roche, MSD, AstraZeneca and Merck. Richard de Boer is on the Australian advisory board for Eli Lilly, Novartis and Pfizer, received speaker honoraria from Novartis and Eli Lilly, and research funding from Novartis and Pfizer. Katharine Cuff has received speaker honoraria from Novartis, is on the advisory board for Novartis, Pfizer and Ipsen, and is part of Amgen education support. Sheau Wen Lok's breast research team has received funding from Novartis, AstraZeneca, Roche and Amgen., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Insomnia and fatigue symptoms are common in breast cancer. Active cancer treatment, such as chemotherapy, appears to be particularly disruptive to sleep. Yet, sleep complaints often go unrecognised and under treated within routine cancer care. The abbreviated delivery of cognitive behavioral therapy for Insomnia (CBTI) and bright light therapy (BLT) may offer accessible and cost-effective sleep treatments in women receiving chemotherapy for breast cancer., Methods: The Sleep, Cancer and Rest (SleepCaRe) Trial is a 6-month multicentre, randomized, controlled, 2 × 2 factorial, superiority, parallel group trial. Women receiving cytotoxic chemotherapy for breast cancer at tertiary Australian hospitals will be randomly assigned 1:1:1:1 to one of four, non-pharmacological sleep interventions: (a) Sleep Hygiene and Education (SHE); (b) CBTI; (c) BLT; (d) CBT-I + BLT combined and simultaneously delivered. Each sleep intervention is delivered over 6 weeks, and will comprise an introductory session, a mid-point phone call, and regular emails. The primary (insomnia, fatigue) and secondary (health-related quality of life, rest activity rhythms, sleep-related impairment) outcomes will be assessed via online questionnaires at five time-points: baseline (t0, prior to intervention), mid-point intervention (t2, Week 4), post-intervention (t3, Week 7), 3-months (t4, Week 18), and 6-months follow-up (t5, Week 30)., Conclusions: This study will report novel data concerning the comparative and combined efficacy of CBT-I and BLT during chemotherapy. Findings will contribute to the development of evidence-based early sleep and fatigue intervention during chemotherapy for breast cancer. Clinical trial information Registered with the Australian New Zealand Clinical Trials Registry (http://anzctr.org.au/), Registration Number: ACTRN12620001133921., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented., Patients and Methods: The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed., Results: The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'., Conclusions: In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile., Competing Interests: Disclosure HSR reports grants from Pfizer, Novartis, Eli Lilly and Company, Genentech/Roche, Macrogenics, Merck, Boehringer Ingelheim, Polyphor, OBI, Odonate, Daiichi, Astra Zeneca, Seattle Genetics, Immunomedics, Sermonix; personal fees from Mylan, Puma, Samsung outside the submitted work. JO reports personal fees from AbbVie Inc., Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Eli Lilly and Company, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche/Genentech, Samsung Bioepis, Sanofi, Seagen, Seattle Genentech, Syndax Pharmaceuticals, Taiho Oncology, Takeda, Synthon outside the submitted work. FB reports personal fees for honoraria and advisory role for Roche, Pfizer, Eli Lilly and Company, and Novartis outside the submitted work. MT reports research grants from JBCRG association, Astellas, AFI technologies, Shionogi, and GL Science; research grants and personal fees from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, Daiichi-Sankyo, AstraZeneca, Shimadzu, Yakult, and Nippon Kyaku; other fees from Kyowa-Kirin and Daiichi-Sankyo; personal and other fees from Eli Lilly and Company, Konica Minolta, Bristol Myers Squibb, Athenex Oncology, Bertis Terumo, and Kansai Medical Net; personal fees for honoraria from MSD, Exact Science, and Novartis; and serves as a board of director for JBCRG association, Organisation for Oncology and Translational Research, and Kyoto Breast Cancer Research Network, outside the submitted work. IB reports grants and research support to institution: AstraZeneca, Roche and Eli Lilly and Company; personal fees for honoraria and advisory role from AstraZeneca, Roche, Novartis, Eisai, Celgene, Pfizer, Eli Lilly and Company, Pierre Fabre and Bristol-Myers Squibb, Veracyte outside the submitted work. MG reports personal fees from MSD, Novartis, GenDrug, and Amgen, outside the submitted work. TY reports grant and other fees from Chugai, Taiho, Nippon Kayaku, Kyowa Kirin; other fees from Eisai, Novartis Pharma, Astra Zeneca, Eli Lilly and Company, Daiichi Sankyo, and Pfizer Japan outside the submitted work. FZ reports personal fees for honoraria, fees for lectures and advisory role for Astra Zeneca, Daiichi, Eli Lilly and Company, Merck, Novartis, Pfizer, and Roche outside the submitted work. MC reports personal fees from Eli Lilly and Company, Novartis, and GT1; other fees from AstraZeneca, Sanofi, Servier, AbbVie, Accord, Pfizer, Seagen, and Daichii Sankyo, outside of the submitted work. BSA, AS, MH, JB, AZ, RW are full-time employees of Eli Lilly and Company and/or Eli Lilly and Company shareholders. SRDJ reports personal fees from AstraZeneca, Eli Lilly and Company, Novartis, Pfizer, Puma Biotechnology, Eisai, and Roche/Genentech; personal fees and other from AstraZeneca, Eli Lilly and Company, Novartis, Pfizer, Puma Biotechnology, and Roche/Genentech, outside the submitted work. MR reports personal fees from Pfizer, Novartis, Eli Lilly and Company, Roche Pharma AG, AstraZeneca, Daiichi Sankyo, Hexal, Novartis, SOMATEX, Seagen, and Pfizer; other fees from Pfizer, Celgene, and Novartis, outside the submitted work. SMT reports grants and personal fees from Eli Lilly and Company during the conduct of the study; grants and personal fees from AstraZeneca, Eli Lilly and Company, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Sanofi, Odonate, Immunomedics/Gilead; grants from Cyclacel; personal fees from Puma, Celldex, Seattle Genetics, Silverback Therapeutics, G1 Therapeutics, Athenex, OncoPep, Kyowa Kirin Pharmaceuticals, Daiichi Sankyo, CytomX, Samsung Bioepsis Inc., Certara, Mersana Therapeutics, OncoSec, Ellipses Pharma, 4D Pharma, Chugai Pharma, Infinity Therapeutics, BeyondSpring Pharmaceuticals outside the submitted work. All other authors have declared no conflicts of interest. Data sharing Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union or after primary publication acceptance, whichever is later. No expiration date for data requests is set once the data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data-sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the online instructions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Going-to-sleep in the supine position in later pregnancy (≥28 weeks) has been identified as a risk factor for stillbirth. Internationally, public awareness campaigns have been undertaken encouraging women to sleep on their side during late pregnancy., Aim: This study aimed to identify sleep practices, attitudes and knowledge in pregnant women, to inform an Australian safe sleeping campaign., Methods: A web-based survey of pregnant women ≥28 weeks' gestation conducted from November 2017 to January 2018. The survey was adapted from international sleep surveys and disseminated via pregnancy websites and social media platforms., Findings: Three hundred and fifty-two women participated. Five (1.6%) reported going to sleep in the supine position. Most (87.8%) had received information on the importance of side-sleeping in pregnancy. Information was received from a variety of sources including maternity care providers (186; 66.2%) and the internet (177; 63.0%). Women were more likely to report going to sleep on their side if they had received advice to do so (OR 2.3; 95% CI 1.0-5.1). Thirteen (10.8%) reported receiving unsafe advice, including changing their going-to-sleep position to the supine position., Discussion: This indicates high level awareness and practice of safe late-pregnancy going-to-sleep position in participants. Opportunities remain for improvement in the information provided, and understanding needs of specific groups including Aboriginal and Torres Strait Islander women., Conclusion: Findings suggest Australian women understand the importance of sleeping position in late pregnancy. Inconsistencies in information provided remain and may be addressed through public awareness campaigns targeting women and their care providers., (Copyright © 2021 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosure MSA reports receipt of consultation fees from Amgen, BMS, Celgene, Clinigen, Eisai, Genomic Health, GSK, Helsinn, Hospira, JnJ, Novartis, Merck, Merck Serono, Mundipharma, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro, Tevam Vifor, G1 Therapeutics and Lilly; receipt of honoraria for symposia lectures from Amgen, Bayer, Schering, Cephalon, Chugai, Eisai, Genomic Health, GSK, Helsinn, Hospira, Ipsen, JnJ Ortho Biotech, Kyowa Hakko Kirin, Merck, Merck Serono, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro, Taiho, Tevam Vifor, G1 Therapeutics and Lilly. CHB reports receipt of honoraria or consultation fees from Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, MSD, AstraZeneca and Bayer; receipt of grants/research support to the institution from AbbVie, Amgen, Astellas Pharma, AstraZeneca, BMS, Celgene, Covance, Lilly, Medivation, Merck Serono, MSD, Novartis, Pfizer, PharmaMar and Roche/Genentech. JB reports receipt of grants/research support grants to Karolinska Institute and University Hospital from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche, Sanofi-Aventis; no personal payments; payment from UpToDate to Asklepios Medicine HB for a chapter on breast cancer prediction. LB reports receipt of grants/research support from Celgene, Genomic Health and Novartis; receipt of honoraria or consultation fees from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre and Roche. FC reports receipt of honoraria or consultation fees from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GSK, MacroGenics, Medscape, MSD, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Seattle Genetics and Teva. JC reports acting as a consultant/advisor for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, MSD, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim and Kyowa Kirin; received honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD and Daiichi Sankyo; received research funding to the institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann-La Roche, Guardant Health, MSD, Pfizer, PIQUR Therapeutics, Puma C and Queen Mary University of London; holds stock, patents and intellectual property for MEDSIR; received travel, accommodation and expenses from Roche, Novartis, Eisai, Pfizer and Daiichi Sankyo. GC reports receipt of honoraria or consultation fees from Roche, Pfizer, Lilly, Novartis and SeaGen; participation in a sponsored speakers' bureau for SeaGen, Pfizer, Lilly and Novartis. NSES reports receipt of grants/research support to institution from Novartis; receipt of honoraria or consultation fees from Novartis, Roche, Pfizer, Lilly and AstraZeneca. ME reports acting in an advisory role for Novartis and Roche. AE reports receipt of grants/research support from AstraZeneca, Roche, Celltrion, Pfizer and Novartis. LF reports receipt of grants/research support from BMS, GSK, Myriad and Novartis; receipt of honoraria or consultation fees from BMS, AstraZeneca, Teva, Novartis, Eisai, Takeda, Pfizer, Lilly, Genomic Health and Myriad. PAF reports receipt of honoraria or consultation fees from AstraZeneca and Novartis; travel for lecture for Pfizer and Ipsen. KG reports receipt of grants/research support from AstraZeneca, Pfizer and BMS; receipt of honoraria or consultation fees from Pfizer, AstraZeneca, Novartis, Nanostring, Merck, Mylan, Genomic Health, Roche and BMS. JG reports receipt of grants/research support from Amgen, Eisai, Genomic Health, Novartis, Pfizer and Roche/Genentech; receipt of honoraria or consultation fees from Daiichi, Eisai, Genomic Health, Ipsen, MacroGenics, MSD, Mylan, Novartis, Onxeo, Pfizer and Roche/Genentech; participation in a sponsored speakers' bureau for Eisai, Genomic Health, Ipsen, Novartis, Pfizer and Roche/Genentech. NH reports receipt of honoraria or consultation fees from Amgen, AstraZeneca, Celgene, Daiichi Sakyo, Lilly, MSD, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal and Seattle Genetics. RK reports receipt of grants/research support from Pfizer Malaysia. BEK reports receipt of grants/research support to institution from Roche; receipt of honoraria for advisory boards and educational presentations as well as travel and meeting expenses from Roche; receipt of honoraria for advisory boards and educational presentations from Novartis. SBK reports receipt of grants/research support to institution from Novartis, Sanofi-Aventis, Kyowa Kirin Inc. and DongKook Pharm Co.; receipt of consultancy fees from Novartis, AstraZeneca, Lilly, Enzychem, Daehwa Pharmaceutical Co. Ltd, ISU ABXIS and Daiichi Sankyo. NUL reports receipt of grants/research support from Genentech and Seattle Genetics; receipt of honoraria or consultation fees from Seattle Genetics, Daiichi Sankyo and Puma. SAM reports receipt of honoraria from Pfizer and Lilly; SN reports receipt of grants/research support from Roche, Pfizer, BMS and Novartis; participation in a sponsored speakers' bureau for Roche, Pfizer, BMS, Merck and Novartis. LN reports receipt of honoraria from Sermonix Oncology Ad Board, Prime Oncology, Sarah Lawrence Lecture, Context advisory board, Oncology Pioneers Science Lecture Series, BCRF programmatic review meeting and CSHL external advisory board meeting. SO reports receipt of grants/research support from Chugai, Eisai, Taiho, Daiichi Sankyo; participation in a sponsored speakers' bureau for Chugai, AstraZeneca, Eisai, Taiho, Pfizer and Lilly. OP reports participation in a sponsored speakers' bureau for Takeda, Roche, Pfizer, Novartis and Lilly. SPS has participated in a speakers' bureau and received honoraria from Roche, AstraZeneca, Novartis, Pfizer, Nanostring and Teva; reports consultancy for Roche, AstraZeneca, Novartis and Pfizer. FPL reports receipt of grants/research support from Roche; receipt of honoraria or consultation fees from Roche, Puma, Pierre Fabre and AstraZeneca. AP reports personal financial interests and lecture fees for Roche, Pfizer, Novartis, Amgen, BMS and Daiichi Sankyo; participation in an advisory role/consultancy for Roche, Pfizer, Novartis, Amgen, BMS, Puma and Oncolytics Biotech; institutional financial interests include contracted research for Novartis, Nanostring, Roche and Boehringer; lecture fees from Nanostring technologies; clinical trials for Novartis, Roche, Boehringer, Daiichi Sankyo, Pfizer, Lilly and Amgen. HSR reports receipt of grants/research support from Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi Sankyo, Eisai, Seattle Genetics, MacroGenics and Immunomedics. ES reports receipt of honoraria or consultation fees from Amgen, AstraZeneca, Clinigen, Egis, Eli Lilly, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz and TLC Biopharmaceuticals; travel support from Amgen, AstraZeneca, Egis, Novartis, Pfizer and Roche; contracted research for Amgen, AstraZeneca, Boehringer, Eli Lilly, Merck, Novartis, Pfizer, Roche and Samsung; holds stock in Eli Lilly. EPW reports receipt of grants/research support from Merck and Genentech/Roche; receipt of honoraria or consultation fees from Carrick Therapeutics, Genentech/Roche, Genomic Health, GSK, Jounce, Leap, Lilly, Merck and Seattle Genetics; research fees to institute from Genentech/Roche and Merck; participation in a scientific advisory board for Leap. BX reports receipt of advisory fees from Novartis and Roche; fees for serving on a speakers' bureau from AstraZeneca, Pfizer, Roche and Eisai. FA, FB, BK, FEL, GWS, CT and TW have not reported any potential conflict of interest. GSB, MJC, LAC, AC, RH, XH, BVO and DAV have declared no significant conflict of interest.

Objective: To comprehensively describe patient-reported, functional and neurophysiological outcomes to elucidate the phenotypic profile of taxane-induced neuropathy., Methods: Taxane-treated patients (n = 47) completed cross-sectional bilateral clinical and sensory assessments and nerve conduction studies. Patients reported symptom severity via Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx13) questionnaire., Results: Symptoms of neuropathy were reported by 81% of patients. On clinical examination, 62% had 2 or more abnormalities, with 20% indicating significant symptomatic and objective neuropathy. Nerve conduction studies were consistent with a sensory predominant axonal neuropathy. However, features more typical of entrapment neuropathy were also present in > 50%, which were not associated with overall severity of chemotherapy-induced peripheral neuropathy (CIPN) or clinical risk factors., Conclusions: There is considerable variation in CIPN phenotypes associated with taxane-treatment. Understanding their clinical associations may assist in identification of patients at risk of severe neurotoxicity. This would enable treatment modification decisions but also limit early cessation of effective anti-cancer treatment in patients with less severe neurological sequelae., Significance: Understanding the CIPN phenotype may inform treatment decisions which could impact clinical and survival outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: 'Bundles of care' are being implemented to improve key practice gaps in perinatal care. As part of our development of a stillbirth prevention bundle, we consulted with Australian maternity care providers., Objective: To gain the insights of Australian maternity care providers to inform the development and implementation of a bundle of care for stillbirth prevention., Methods: A 2018 on-line survey of hospitals providing maternity services included 55 questions incorporating multiple choice, Likert items and open text. A senior clinician at each site completed the survey. The survey asked questions about practices related to fetal growth restriction, decreased fetal movements, smoking cessation, intrapartum fetal monitoring, maternal sleep position and perinatal mortality audit. The objectives were to assess which elements of care were most valued; best practice frequency; and, barriers and enablers to implementation., Results: 227 hospitals were invited with 83 (37%) responding. All proposed elements were perceived as important. Hospitals were least likely to follow best practice recommendations "all the time" for smoking cessation support (<50%), risk assessment for fetal growth restriction (<40%) and advice on sleep position (<20%). Time constraints, absence of clear guidelines and lack of continuity of carer were recognised as barriers to implementation across care practices., Conclusions: Areas for practice improvement were evident. All elements of care were valued, with increasing awareness of safe sleeping position perceived as less important. There is strong support from maternity care providers across Australia for a bundle of care to reduce stillbirth., (Copyright © 2019 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Objective: Family caregivers can, at times, add complexity to clinical encounters. Difficult family caregivers and dynamics may: derail consultation communication, reduce patient autonomy, and compromise effective clinical care. A paucity of practical strategies guiding effective clinician-family communication exists. This study aimed to develop and evaluate the first comprehensive, evidence-based guidelines (the TRIO guidelines) for oncology physicians and nurses to better manage several complex/challenging situations involving family members., Methods: TRIO Guidelines were based on a comprehensive review of literature, relevant guidelines, and feedback from an expert advisory group (n = 10). Draft guidelines underwent two rounds of evaluation via an online Delphi consensus process involving international experts (n = 35)., Results: Guidelines incorporate topic areas, strategies, and sub-strategies on managing challenging family involvement (7 topics). Example wording, behaviours and level of evidence are provided., Conclusion: Challenging triadic interactions require skillful navigation, and the TRIO Guidelines provide clear, specific, and evidence-based strategies for clinicians to utilise in these potentially stressful encounters. Training based on these guidelines may improve both patient care and clinician confidence., Practice Implications: Implementation of these guidelines into medical/nursing curricula and as a component of continuing professional development programs will likely be highly beneficial., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Family caregivers regularly attend medical consultations and are often involved in decision-making; however, there are few practical strategies to guide effective communication for the clinician-patient-family trio. We aimed to develop and evaluate the first comprehensive guidelines for oncology physicians and nurses, on how to positively and effectively involve family caregivers of adult patients in consultations and patient care (TRIO Guidelines-1) and how to manage challenging interactions with family caregivers (TRIO Guidelines-2)., Methods: The TRIO Guidelines were based on a comprehensive literature review and input from an expert advisory group (n = 10). They underwent two rounds of formal evaluation via an online Delphi consensus process involving international experts (n = 35), and a subset were piloted with 24 breast cancer clinicians in a workshop format., Results: TRIO Guidelines-1 incorporate strategies and sub-strategies on facilitating collaborative and effective family involvement (6 topics). Example wording, behaviours, and level of evidence are provided throughout. All 24 clinicians rated the guidelines as helpful after the pilot workshop., Conclusion: These guidelines will be a useful educational tool for clinicians and medical/nursing students., Practice Implications: By equipping clinicians with strategies to facilitate effective and collaborative family engagement, the TRIO Guidelines have the potential to transform communication in clinical practice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chemotherapy induced peripheral neuropathy (CIPN) is a significant toxicity of cancer treatment, with the potential to affect long-term function and quality of life in cancer survivors. There remains a lack of consensus around optimal assessment techniques. While current approaches to CIPN assessment are focused on clinical grading scales, it is becoming increasingly evident that a more comprehensive multimodal assessment package is necessary to accurately characterise the impact of CIPN as well as gauge the utility of neuroprotective mechanisms. Neurophysiological techniques provide objective biomarkers and may enable early detection of toxicity while patient reported outcomes are necessary to determine the significance of symptoms to individual patients. In addition to providing an objective assessment, clinical neurophysiological techniques provide important insights into the contributory pathophysiological mechanisms of CIPN with different chemotherapy agents. There is a paucity of implementation of these techniques in the clinical trial setting. The present Review aims to facilitate the use of neurophysiological studies as part of comprehensive assessment packages for the monitoring of CIPN by summarising current understanding of neurophysiological changes that underlie the development of neuropathy, clinical presentations and patient reported outcomes as well as advantages and limitations of current techniques for the neurophysiological assessment of CIPN., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy., Patients and Methods: This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety., Results: Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole., Conclusion: These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy., Clinical Trials Number: Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: Managing symptom clusters or multiple concurrent symptoms in patients with advanced cancer remains a clinical challenge. The optimal processes constituting effective management of symptom clusters remain uncertain., Objectives: To describe the attitudes and strategies of clinicians in managing multiple co-occurring symptoms in patients with advanced cancer., Methods: Semistructured interviews were conducted with 48 clinicians (palliative care physicians [n = 10], oncologists [n = 6], general practitioners [n = 6], nurses [n = 12], and allied health providers [n = 14]), purposively recruited from two acute hospitals, two palliative care centers, and four community general practices in Sydney, Australia. Transcripts were analyzed using thematic analysis and adapted grounded theory., Results: Six themes were identified: uncertainty in decision making (inadequacy of scientific evidence, relying on experiential knowledge, and pressure to optimize care); attunement to patient and family (sensitivity to multiple cues, prioritizing individual preferences, addressing psychosocial and physical interactions, and opening Pandora's box); deciphering cause to guide intervention (disaggregating symptoms and interactions, flexibility in assessment, and curtailing investigative intrusiveness); balancing complexities in medical management (trading off side effects, minimizing mismatched goals, and urgency in resolving severe symptoms); fostering hope and empowerment (allaying fear of the unknown, encouraging meaning making, championing patient empowerment, and truth telling); and depending on multidisciplinary expertise (maximizing knowledge exchange, sharing management responsibility, contending with hierarchical tensions, and isolation and discontinuity of care)., Conclusion: Management of symptom clusters, as both an art and a science, is currently fraught with uncertainty in decision making. Strengthening multidisciplinary collaboration, continuity of care, more pragmatic planning of clinical trials to address more than one symptom, and training in symptom cluster management are required., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Several complex treatment decisions may be offered to women with early stage breast cancer, about a range of treatments from different modalities including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids can facilitate shared decision-making and improve decision-related outcomes. We aimed to systematically identify, describe and appraise the literature on treatment decision aids for women with early breast cancer, synthesise the data and identify breast cancer decisions that lack a decision aid. A prospectively developed search strategy was applied to MEDLINE, the Cochrane databases, EMBASE, PsycINFO, Web of Science and abstract databases from major conferences. Data were extracted into a pre-piloted form. Quality and risk of bias were measured using Qualsyst criteria. Results were synthesised into narrative format. Thirty-three eligible articles were identified, evaluating 23 individual treatment decision aids, comprising 13 randomised controlled trial reports, seven non-randomised comparative studies, eight single-arm pre-post studies and five cross-sectional studies. The decisions addressed by these decision aids were: breast conserving surgery versus mastectomy (+/- reconstruction); use of chemotherapy and/or endocrine therapy; radiotherapy; and fertility preservation. Outcome measures were heterogeneous, precluding meta-analysis. Decisional conflict decreased, and knowledge and satisfaction increased, without any change in anxiety or depression, in most studies. No studies were identified that evaluated decision aids for neoadjuvant systemic therapy, or contralateral prophylactic mastectomy. Decision aids are available and improved decision-related outcomes for many breast cancer treatment decisions including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids for neoadjuvant systemic therapy and contralateral prophylactic mastectomy could not be found, and may be warranted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy., Methods: Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety., Results: 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer., Conclusion: Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Poor prognosis is difficult to impart, particularly across a cultural divide. This study compared prognostic communication with immigrants (with and without interpreters) versus native-born patients in audio-taped oncology consultations., Methods: Ten oncologists, 78 patients (31 Australian-born, 47 immigrants) and 115 family members participated. The first two consultations after diagnosis of incurable disease were audiotaped, transcribed and coded. 142 consultations were included in the analysis., Results: Fifty percent of doctor and 59% of patient prognostic speech units were not interpreted or interpreted non-equivalently when an interpreter was present. Immigrant status predicted few prognostic facts, and oncologist characteristics no prognostic facts, disclosed. Oncologists were significantly less likely to convey hope to immigrants (p=0.0004), and more likely to use medical jargon (p=0.009) than with Australian-born patients. Incurable disease status and a limited life span were commonly acknowledged, generally with no timeframe provided. Physical issues were discussed more commonly than emotional aspects., Conclusions: While culture did not appear to influence doctor speech, interpreters filtered or blocked much prognostic communication., Practice Implications: Initiatives to empower all patients to attain needed information, optimise communication when an interpreter is present and train cancer health professionals in culturally appropriate care, are urgently required., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Context: Cancer pain is a common, burdensome problem, which is not well managed despite evidence-based guidelines., Objectives: To develop insights for managing barriers and optimizing facilitators to adult cancer pain assessment and management within a comprehensive framework of patient care., Methods: We undertook a systematic review and synthesis of qualitative studies. Medline, PsycINFO, Embase, AMED, CINAHL, and Sociological Abstracts were searched from May 20 to 26, 2011. To be included, the articles had to be published in a peer-reviewed journal since 2000; written in English; and report original qualitative studies on the perspectives of patients, their significant others, or health care providers. Article quality was rated using the checklist of Kitto et al. Thematic synthesis followed a three-stage approach using Evidence for Policy and Practice Information and Co-ordinating Centre-Reviewer 4 software: 1) free line-by-line coding of "Results," 2) organization into "descriptive" themes, and 3) development of "analytical" themes informative to our objective. At Stage 3, a conceptual framework was selected from the peer-reviewed literature according to prima facie "fit" for descriptive themes., Results: Of 659 articles screened, 70 met the criteria, reporting 65 studies with 48 patient, 19 caregiver, and 21 health care provider samples. Authors rarely reported reflexivity or negative cases. Mead and Bower's model of patient-centered care accommodated 85% of the descriptive themes; 12% more related to the caregiver and service/system factors. Three themes could not be accommodated., Conclusion: Findings highlight the need to integrate patient/family education within improved communication, individualize care, use more nonpharmacological strategies, empower patients/families to self-manage pain, and reorganize multidisciplinary roles around patient-centered care and outcomes. These conclusions require validation via consensus and intervention trials., (Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Background: Prolonged fatigue after cancer treatment is common. The pathophysiology of such post-cancer fatigue (PCF) is unknown, although cross-sectional studies suggest increased pro-inflammatory cytokine production. This study investigated the association between cytokine levels and fatigue from the time of treatment to 12 months later., Patients and Methods: A representative nested case-control series was derived from a prospective cohort of women treated for early-stage breast cancer, including 13 PCF cases and 15 matched control subjects who recovered uneventfully. Serum levels and in vitro production of the cytokines interleukin (IL)-1α, IL-2, interferon (IFN)-γ, IL-4, IL-6, IL-10, IL-12, and tumour necrosis factor (TNF)-β were measured by multiplex immunoassay in longitudinally collected samples. In addition, serum levels of neopterin and the anti-inflammatory regulators, IL-1 receptor antagonist, sIL-6R, and sTNF-rII, were assayed by enzyme-linked immunosorbent assay. Flow cytometric analysis of activated leukocyte subsets was performed., Results: No significant differences in any of these parameters were found between cases and control subjects. Cytokine levels and symptoms showed no clear correlation pattern., Conclusion: The findings in this well-characterised subject group argue against the notion that PCF is mediated by peripheral inflammation.

Background: Many anticancer drugs are only available to Australian patients at a significant cost in the time preceding approval for government subsidy. Studies indicate that many oncologists find it difficult to discuss high-cost drugs (HCDs) with patients whom they believe are unable to afford treatment, thereby limiting treatment choices. We sought to identify the information needs and communication preferences of women with breast cancer regarding HCDs., Patients and Methods: An e-mail invitation was sent to 317 members of Breast Cancer Network Australia. Forty-seven subjects participated in telephone interviews on the basis of a structured questionnaire regarding personal experience with HCD discussions and information preferences., Results: Participants considered an out-of-pocket cost of $50/week to be a HCD. Only 28% had previously discussed HCD treatment with their oncologist; however, 96% of participants wanted to discuss an expensive drug as an option, even if they were unlikely able to afford it., Conclusions: Women with breast cancer have a strong desire to be active participants in their cancer treatment and wish to be fully informed of potential treatment options, including HCDs. Nondisclosure of information, including HCDs, can result in patient dissatisfaction.

This paper reviews the recent literature regarding the time-dependent computational fluid dynamics (CFD) analyses of blood flow through implanted coronary stents. The in vivo processes which result in arterial restenosis are identified. The definition and range of the computationally predicted variables which are believed to stimulate the restenosis processes are evaluated. The reviewed literature is subdivided into effect-based in which the effects of altering the flow model are investigated and design-based in which different geometric stent configurations are compared. Finally, conclusions are made regarding the body of work reviewed and recommendations are provided for future work in this field., (2010 Elsevier Ltd. All rights reserved.)

Objective: Preferences of women who had completed adjuvant chemotherapy for early breast cancer were compared with those of their partners by determining the smallest benefits they judged sufficient to make adjuvant chemotherapy worthwhile., Methods: Forty-six women and their partners were interviewed separately, 3-34 months after completing adjuvant chemotherapy. Preferences were elicited using four sets of validated, hypothetical trade-off scenarios about the possible benefits of adjuvant chemotherapy on survival times (5 and 15 years) and survival rates (65% and 85% at 5 years). Agreement within couples was assessed with the intraclass correlation coefficient (ICC). Associations between baseline characteristics, preferences, and agreement within couples were assessed with linear regression after normal score transformation., Results: The mean age of the women was 57 years and of their partners' was 60. Most couples were married (91%). Benefits of an extra 1 day or 0.1% were judged sufficient to make adjuvant chemotherapy worthwhile by 59-72% of women and 54-59% of partners. Agreement was exact in 35-41% of couples and approximate in 59-83%. Agreement was better for scenarios with a worse prognosis (ICC 0.67 and 0.35) than for scenarios with a better prognosis (ICC 0.13 and 0.05). Having dependent children was associated with partners requiring larger benefits but patients requiring smaller benefits to make adjuvant chemotherapy worthwhile (interaction P=0.001)., Conclusion: Patients' and partners' preferences for adjuvant chemotherapy differed and were influenced by considerations other than length and quality of life., Practice Implications: Clinicians who are aware of these differences can tailor discussions to ensure that all interested parties understand and agree on the goals and benefits of treatment.

Thalidomide is a racemate with potentially different pharmacokinetics and pharmacodynamics of the component (+)-(R)- and (-)-(S)-thalidomide enantiomers. As part of a project on the adjunctive effects of thalidomide and cytotoxic agents, a method for the chiral separation and quantitation of thalidomide was developed and validated. Thalidomide in relevant serum and tissue homogenate samples was stabilized by buffering with an equal volume of citrate-phosphate buffer (pH 2, 0.2M), and stored at -80 degrees C pending assay. The thalidomide enantiomers, extracted from the samples with diethyl ether, were well separated on a chiral HPLC column of vancomycin stationary phase and a mobile phase of 14% acetonitrile in 20 mM ammonium formate adjusted to pH 5.4; their concentrations were determined with phenacetin as internal standard at 220 nm detection. Over a thalidomide concentration range of 0.1-20 microg/ml, assay precision was 1-5% (CV) for both enantiomers, and calibration curves were linear with all correlation coefficients being >0.99. The estimated limit of quantification for both enantiomers was 0.05 microg/ml with 0.2-0.6 ml serum samples. Thalidomide in rat and human serum, acidified and stored as described above, was found to be chemically and chirally stable over 1 year. The method has been successfully applied to serum samples from human patients undergoing thalidomide treatment for mesothelioma, and to serum, blood and tissue samples from a laboratory rodent model using transplanted 9l gliosarcoma. Enantioselectivity in thalidomide pharmacokinetics has been found, thereby reinforcing the need for considering the relevance of chirality in thalidomide pharmacology.

Background: Studies of women who had adjuvant chemotherapy for early breast cancer 10-20 years ago showed that many judged small benefits sufficient to make it worthwhile. Indications, regimens and supportive care have changed. We sought the preferences of contemporary women who received similar chemotherapy., Patients and Methods: Ninety-seven consecutive consenting women who completed adjuvant chemotherapy for early breast cancer 3-34 months previously were interviewed. Preferences were elicited with a structured, scripted interview using the trade-off method. Women were presented with four hypothetical scenarios based on known life expectancies (5 and 15 years) and survival rates (65% and 85% at 5 years) without adjuvant chemotherapy., Results: Improvements of an additional year in life expectancy or 3% in survival rates were judged sufficient to make adjuvant chemotherapy worthwhile by 68-84% of women. Half the women judged 1 day or 0.1% sufficient to make adjuvant chemotherapy worthwhile. Recollections of better well-being during adjuvant chemotherapy, having dependants and having a friend or relative who died from cancer were independently associated with judging smaller benefits sufficient to make adjuvant chemotherapy worthwhile (all P < 0.05)., Conclusions: Preferences were highly variable, but the benefits judged sufficient to make adjuvant chemotherapy worthwhile were even smaller than those found in previous studies. Preferences were influenced by factors other than direct benefits and harms of chemotherapy.

Background: Raf is a proto-oncogene that is activated in response to growth factors or phorbol esters, and is thought to activate MAP kinase kinase-1 (MKK1) and hence the classical MAP kinase (MAPK) cascade., Results: The compound ZM 336372 is identified as a potent and specific inhibitor of Raf isoforms in vitro. Paradoxically, exposure of cells to ZM 336372 induces > 100-fold activation of c-Raf (measured in the absence of compound), but without triggering any activation of MKK1 or p42 MAPK/ERK2. The ZM 336372-induced activation of c-Raf occurs without any increase in the GTP-loading of Ras and is not prevented by inhibition of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase. ZM 336372 does not prevent growth factor or phorbol ester induced activation of MKK1 or p42 MAPK/ERK2, or reverse the phenotype of Ras- or Raf-transformed cell lines. The only other protein kinase inhibited by ZM 336372 out of 20 tested was SAPK2/p38. Although ZM 336372 is structurally unrelated to SB 203580, a potent inhibitor of SAPK2/p38, the mutation of Thr106-->Met made SAPK2/p38 insensitive to ZM 336372 as well as to SB 203580., Conclusions: Raf appears to suppress its own activation by a novel feedback loop, such that inhibition is always counterbalanced by reactivation. These observations imply that some agonists reported to trigger the cellular activation of c-Raf might actually be inhibitors of this enzyme, and that compounds which inhibit the kinase activity of Raf might not be useful as anticancer drugs. The binding sites for ZM 336372 and SB 203580 on Raf and SAPK2/p38 are likely to overlap.

The prevalence and correlates of psychological distress were examined in a sample of 171 female sex workers in Queensland. It was found that 28 per cent were above the GHQ-28 threshold for mild psychiatric morbidity, a rate that is not appreciably different from that of women in the general community. The sample included only eight street sex workers, all of whom reported significant distress. Logistic regression analyses showed that a history of injecting drug use, an early age at leaving home and wanting to leave the sex industry were independent predictors of poor mental health. Distressed sex workers reported fewer sexual health examinations and less consistent condom use with their clients than those who were not distressed.

Nonparticipants in epidemiological studies may differ in important respects from participants but the magnitude of this potential bias is rarely quantified. This study estimates the effect of nonparticipation on estimates of mental health problems following stillbirth, neonatal death or sudden infant death syndrome. Of 805 families approached, 512 (64 per cent) were recruited, of whom 77 per cent of mothers and 71 per cent of fathers completed four study interviews. Younger, unmarried, unemployed parents without private health insurance were less often recruited, and even if recruited, were less likely to complete the interview. By evaluating several possible scenarios, we estimated that had mothers lost to follow-up remained in the study, anxiety rates would have varied by no more than +/-4 per cent. Relative risks associated with bereaved-control comparisons would have differed little from the observed estimate of 2.33. Estimating the effects of initial nonresponse is more difficult but the adoption of a worst-case scenario produced a relative risk of 3.47. Despite systematic nonparticipation suggestive of social disadvantage, attrition-related bias may have had only a modest effect on anxiety and depression rate estimates. However, this may not be the case when sample loss is high, when associations between attrition and outcome are strong, and when attrition-related behaviour differs across comparison groups.

Human milk fat is well absorbed despite its large concentration of long-chain saturated fatty acids (LCSFA), particularly palmitic acid. The superior absorption has been ascribed in part to the uncommonly high proportion of the palmitic acid in the sn-2 position of the triglycerides, 70% in human milk triglycerides compared with 10-15% in the fats and oils commonly used in infant formula blends. Colipase-dependent pancreatic lipase selectively hydrolyzes the fatty acids at the sn-1 and 3 positions, yielding free fatty acids and the 2-monoglyceride, which are absorbable. Free palmitic acid, but not monopalmitin, can be lost as calcium soaps in the feces. The present study demonstrated that mixtures of coconut oil and palm olein are better absorbed by rats if the proportion of LCSFA in the sn-2 position is increased by the process of chemical randomization, in which the fatty acids of the native oils are redistributed equally to all three positions in the rearranged triglycerides. The fecal excretion of total fatty acids, essentially LCSFA, from the mixtures in which the oils were randomized together (corandomized) was 30 to 60% less than from the mixtures of native oils.

Galactosyltransferase (GT) was isolated from human malignant ascitic fluid, and the ion-exchange and lectin affinity chromatographic behaviour of the two isoforms, GTI and GTII, investigated. The effect of neuraminidase on the binding to DEAE-Sephacel and various lectins suggests that GTII, the so-called cancer-specific isoform, is a more sialylated form of GTI.

Cacodylate buffer, frequently used in the assay of galactosyltransferase, causes inhibition of enzyme purified from human pleural effusion. The inhibition is reflected by an increase in the Km (UDP-galactose) and a decrease in Vmax and cannot be reversed by the addition of 2-mercaptoethanol. It is suggested that alternative buffers be used for the study of the enzyme.

Galactosyltransferase was isolated from human malignant ascites by ammonium sulphate precipitation, alpha-lactalbumin affinity chromatography and by the removal of contaminating immunoglobulins with protein A chromatography. Two isoforms of galactosyltransferase were separated by DEAE chromatography, and partially characterised by gel filtration, non-denaturing polyacrylamide gel electrophoresis, concanavalin A binding and enzyme kinetics. The two forms isolated were compared with the isoenzymes previously described and the biochemical basis for the difference between the two forms discussed.