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Abstract Background Fiji, a Pacific Island nation of 884,887 (2017 census), has experienced a prolonged epidemiological transition. This study examines trends in mortality and life expectancy (LE) in Fiji by sex and ethnicity over 1996–2017, with comparisons to published estimates. Methods Trends in infant mortality rates (IMR), under-5 mortality (U5M), adult mortality (probability of dying), LE (at birth) and directly age-standardised death rates (DASRs) by sex and ethnicity, are calculated (with 95% confidence limits) using unit death records from the Fiji Ministry of Health and Medical Services. The LE gap between populations, or within populations over time, is examined using decomposition by age. Period trends are assessed for statistical significance using linear regression. Results Over 1996–98 to 2014–17: IMR and U5M for i-Taukei and Fijians of Indian descent declined; U5M decline for i-Taukei (24.6 to 20.1/1000 live births) was significant (p = 0.016). Mortality (15–59 years) for i-Taukei males was unchanged at 27% but declined for Indians 33 to 30% (p = 0.101). Mortality for i-Taukei females increased 22 to 24% (p = 0.011) but declined for Indians 20 to 18% (p = 0.240). DASRs 1996–2017 were lower for i-Taukei (9.3 to 8.2/1000 population) than Indian males (10.6 to 9.8/1000). DASRs declined for i-Taukei (both sexes, p 0.05). Over 22 years, LE at birth increased by 1 year or less (p = 0.030 in male i-Taukei). In 2014–17, LE (years) for males was: i-Taukei 64.9, Indians 63.5; and females: i-Taukei 67.0 and Indians 68.2. Mortality changes in most 5-year age groups increased or decreased the LE gap less than 10 weeks over 22 years. Compared to international agency reports, 2014–17 empirical LE estimates (males 64.7, females 67.8) were lower, as was IMR. Conclusions Based on empirical data, LE in Fiji has minimally improved over 1996–2017, and is lower than some international agencies report. Adult mortality was higher in Indian than i-Taukei men, and higher in i-Taukei than Indian women. Exclusion of stillbirths resulted in IMRs lower than previously reported. Differing mortality trends in subgroups highlight the need to collect census and health data by ethnicity and sex, to monitor health outcomes and inform resource allocation.

Translational RelevanceEvaluation of targeted therapies is urgently needed for the majority of patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC) who progress after immunochemotherapy. Erlotinib, a targeted inhibitor of epidermal growth factor receptor pathway, lacks FDA approval in HNSCC due to inadequate tumor response. This study identifies two potential avenues to improve tumor response to erlotinib among patients with HNSCC. For the first time, this study shows that an increased erlotinib dose of 300 mg in smokers is well-tolerated and produces similar plasma drug concentration as the regular dose of 150 mg in non-smokers, with increased study-specific defined tumor response. The study also highlights the opportunity for improved patient selection for erlotinib treatment by demonstrating that early in-treatment [18]FDG PET/CT is a potential predictor of tumor response, with robust statistical correlations between metabolic changes on early in-treatment PET (4-7 days through treatment) and anatomic response measured by end-of-treatment CT.PurposePatients with advanced HNSCC failing immunochemotherapy have no standard treatment options. Accelerating the investigation of targeted drug therapies is imperative. Treatment with erlotinib produced low response rates in HNSCC. This study investigates the possibility of improved treatment response through patient smoking status-based erlotinib dose optimization, and through early in-treatment [18]FDG PET evaluation to differentiate responders from non-responders.Experimental designIn this window-of-opportunity study, patients with operable HNSCC received neoadjuvant erlotinib with dose determined by smoking status: 150 mg (E150) for non-smokers and 300 mg (E300) for active smokers. Plasma erlotinib levels were measured using mass spectrometry. Patients underwent PET/CT before treatment, between days 4-7 of treatment, and before surgery (post-treatment). Response was measured by diagnostic CT and was defined as decrease in maximum tumor diameter by ≥ 20% (responders), 10-19% (minimum-responders), and < 10% (non-responders).ResultsNineteen patients completed treatment, ten of whom were smokers. There were eleven responders, five minimum-responders, and three non-responders. Tumor response and plasma erlotinib levels were similar between the E150 and E300 patient groups. The percentage change on early PET/CT and post-treatment PET/CT compared to pre-treatment PET/CT were significantly correlated with the radiologic response on post-treatment CTs: R=0.63, p=0.0041 and R=0.71, p=0.00094, respectively.ConclusionThis pilot study suggests that early in-treatment PET/CT can predict response to erlotinib, and treatment with erlotinib dose adjusted according to smoking status is well-tolerated and may improve treatment response in HNSCC. These findings could help optimize erlotinib treatment in HNSCC and should be further investigated.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT00601913, identifier NCT00601913.

Abstract Background Virtual Learning Collaboratives (VLC), learning communities focused on a common purpose, are used frequently in healthcare settings to implement best practices. Yet, there is limited research testing the effectiveness of this approach compared to other implementation strategies. This study evaluates the effectiveness of a VLC compared to Technical Assistance (TA) among community oncology practices implementing ENABLE (Educate, Nurture, Advise, Before Life Ends), an evidence-based, early palliative care telehealth, psycho-educational intervention for patients with newly diagnosed advanced cancer and their caregivers. Methods Using Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) and Proctor’s Implementation Outcomes Frameworks, this two-arm hybrid type-III cluster-randomized controlled trial (RCT) will compare two implementation strategies, VLC versus TA, among the 48 National Cancer Institute Community Oncology Research Program (NCORP) practice clusters that have not historically provided palliative care to all patients with advanced cancer. Three cohorts of practice clusters will be randomized to the study arms. Each practice cluster will recruit 15–27 patients and a family caregiver to participate in ENABLE. The primary study outcome is ENABLE uptake (patient level), i.e., the proportion of eligible patients who complete the ENABLE program (receive a palliative care assessment and complete the six ENABLE sessions over 12 weeks). The secondary outcome is overall program implementation (practice cluster level), as measured by the General Organizational Index at baseline, 6, and 12 months. Exploratory aims assess patient and caregiver mood and quality of life outcomes at baseline, 12, and 24 weeks. Practice cluster randomization will seek to keep the proportion of rural practices, practice sizes, and minority patients seen within each practice balanced across the two study arms. Discussion This study will advance the field of implementation science by evaluating VLC effectiveness, a commonly used but understudied, implementation strategy. The study will advance the field of palliative care by building the capacity and infrastructure to implement an early palliative care program in community oncology practices. Trial registration Clinicaltrials.gov . NCT04062552; Pre-results. Registered: August 20, 2019. https://clinicaltrials.gov/ct2/show/NCT04062552?term=NCT04062552&draw=2&rank=1

Abstract Background Tonga is a South Pacific Island country with a population of 100,651 (2016 Census). This study examines Tongan infant mortality rates (IMR), under-five mortality rates (U5MR), adult mortality and life expectancy (LE) at birth from 2010 to 2018 using a recent collation of empirical mortality data over the past decade for comparison with other previously published mortality estimates. Methods Routinely collected mortality data for 2010–2018 from the Ministry of Health, national (Vaiola) hospital, community nursing reports, and the Civil Registry, were consolidated by deterministic and probabilistic linkage of individual death records. Completeness of empirical mortality reporting was assessed by capture-recapture analysis. The reconciled data were aggregated into triennia to reduce stochastic variation, and used to estimate IMR and U5MR (per 1000 live births), adult mortality (15–59, 15–34, 35–59, and 15–64 years), and LE at birth, employing the hypothetical cohort method (with statistical testing). Mortality trends and differences were assessed by Poisson regression. Mortality findings were compared with published national and international agency estimates. Results Over the three triennia in 2010–2018, levels varied minimally for IMR (12–14) and U5MR (15–19) per 1000 births (both ns, p > 0.05), and also for male LE at birth of 64–65 years, and female LE at birth 69–70 years. Cumulated risks of adult mortality were significantly higher in men than women; period mortality increases in 15–59-year women from 18 to 21% were significant (p 95%. International agencies reported generally comparable estimates of IMR and U5MR, with varying uncertainty intervals; but they reported significantly lower adult mortality and higher LE than the empirical estimates from this study. Conclusions Life expectancy in Tonga over 2010–2018 has remained relatively low and static, with low IMR and U5MR, indicating the substantial impact from premature adult mortality. This analysis of empirical data (> 95% complete) indicates lower LE and higher premature adult mortality than previously reported by international agencies using indirect and modelled methods. Continued integration of mortality recording and data systems in Tonga is important for improving the completeness and accuracy of mortality estimation for local health monitoring and planning.

Future Force Design (FFD) is a strategic planning activity that decides the programming of defence capability options. This is a complex problem faced by the Australian Department of Defence (DoD) and requires the simultaneous selection and scheduling of projects. Specifically, this is a NP-hard problem known as the Project Portfolio Selection and Scheduling Problem (PPSSP). While the PPSSP is a complex problem itself, its complexity is further increased when coupled with the additional characteristics that arise in the context of defence-oriented planning, such as long planning periods and complex operational constraints. As a result, many previous studies examined only a small number of projects over a short planning period and are largely unsuitable for the scale required in the defence sector. To address this issue, two primary contributions are made in this paper. Firstly, this study describes a complex practical PPSSP, inspired by the FFD process, and develops a corresponding mathematical model. Problem instances are derived from real-world, publicly-available defence data. Secondly, to address instances of the problem, two existing meta-heuristics are considered and a hybrid, multi-population approach is proposed. Results are compared against those attained by a commercial exact solver and indicate that there is no statistically significant difference in performance between the proposed multi-population approach and the exact solver. A key benefit of the proposed meta-heuristic approach is that its run time is not significantly influenced by the complexity of the problem instance. Additionally, many interesting practical insights regarding the solution of selection and scheduling problems are uncovered.