Building the capacity of rural allied health generalists through online postgraduate education: a qualitative evaluation

Introduction: Workforce development is a key strategy for building the capacity and capability of a workforce. Accordingly, rural and remote practising allied health professionals require relevant and accessible continuing professional development to enhance their knowledge and skills and improve consumer health outcomes. This study explored the impact of an online postgraduate allied health rural generalist education program, from the perspective of allied health professionals participating in the program and their supervisors and managers. Methods: A qualitative, exploratory descriptive study design was employed using semistructured interviews. This study formed the qualitative component of a larger convergent mixed-methods evaluation study aimed at evaluating the reach, quality and impact of an online rural generalist education program for allied health professionals in Australia. Allied health professionals from seven professions enrolled in an online postgraduate rural generalist education program, the rural generalist program (RGP). Their designated work-based supervisors and their managers who were responsible for the operational management of the study sites were invited to participate in the study. All participants were employed in rural and remote health services in 10 sites across four Australian states. Study participants’ experience and perceptions of the impact of the RGP on themselves, the healthcare service and the broader community were explored using semistructured interviews. Data were thematically analysed site by site, then across sites using Braun and Clarke’s (2012) systematic six-phase approach. Provisional codes were generated and iteratively compared, contrasted and collapsed into secondary, more advanced codes until final themes and subthemes were developed. Results: Semistructured interviews were conducted with 23 allied health professionals enrolled in the RGP and their 27 work-based supervisors and managers across the 10 study sites. Three final themes were identified that describe the impact of the RGP: building capability as rural generalist allied health professionals; recruiting and building a rural workforce; enhancing healthcare services and consumer outcomes. Conclusion: Allied health professionals working in rural and remote locations valued the RGP because it provided accessible postgraduate education that aligned with their professional and clinical needs. Integrated into a supportive, well-structured development pathway, the experience potentiated learning and facilitated safe clinical practice that met the needs of consumers and organisations. The findings demonstrate that effective work-integrated learning strategies can enhance the development of essential capabilities for rural practice and support early-career allied health professionals’ transition to rural and remote practice. These experiences can engage allied health professionals in a way that engenders a desire to remain working in rural and remote contexts

Symptomatic benefit of momelotinib in patients with myelofibrosis: Results from the SIMPLIFY phase III studies

Momelotinib; Myelofibrosis; Patient-reported outcomesMomelotinib; Mielofibrosi; Resultats informats pel pacientMomelotinib; Mielofibrosis; Resultados informados por el pacienteBackground Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy. Methods Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to complement the interpretation of the landmark symptom results in the completed phase III SIMPLIFY studies of momelotinib in MF. MMRM compared mean change in TSS from baseline with Week 24 using data from all patient visits. Generalized estimating equations were used to estimate item-level odds ratios using multiple predictive imputations for missing data. Results Momelotinib and ruxolitinib groups reported similar overall symptom improvements, with a TSS difference of <1.5 points between groups for each post-baseline visit in SIMPLIFY-1. In SIMPLIFY-2, the improvement in TSS observed in momelotinib-treated patients was consistent with that observed in SIMPLIFY-1, whereas progressive TSS deterioration was observed with control. Item-level scores were heterogeneous in both studies. A similar and greater proportion of momelotinib-treated patients were categorized as “improved” or “stable” compared with control in SIMPLIFY-1 and SIMPLIFY-2, respectively. Odds ratios for between-group comparison ranged from 0.75 to 1.21 in SIMPLIFY-1, demonstrating similarity in likelihood of symptom improvement. In SIMPLIFY-2, the likelihood of symptom improvement in each item was higher in the momelotinib arm. Conclusions These findings suggest that momelotinib provides clinically relevant symptom benefits in the JAK inhibitor-naïve and JAK inhibitor-exposed settings.SIMPLIFY-1 and SIMPLIFY-2 were sponsored by Gilead Sciences. This analysis was sponsored by Sierra Oncology, a GSK company

Saharan dust plume charging observed over the UK

A plume of Saharan dust and Iberian smoke was carried across the southern UK on 16th October 2017, entrained into an Atlantic cyclone which had originated as Hurricane Ophelia. The dust plume aloft was widely noticed as it was sufficiently dense to redden the visual appearance of the sun. Time series of backscatter from ceilometers at Reading and Chilbolton show two plumes: one carried upwards to 2.5 km, and another below 800m into the boundary layer, with a clear slot between. Steady descent of particles at about 50 cms−1 continued throughout the morning, and coarse mode particles reached the surface. Plumes containing dust are frequently observed to be strongly charged,often through frictional effects. This plume passed over atmospheric electric field sensors at Bristol, Chilbolton and Reading. Consistent measurements at these three sites indicated negative plume charge. The lower edge plume charge density was (−8.0±3.3) nCm−2, which is several times greater than that typical for stratiform water clouds, implying an active in situ charge generation mechanism such as turbulent triboelectrification. A meteorological radiosonde measuring temperature and humidity was launched into the plume at 1412 UTC, specially instrumented with charge and turbulence sensors. This detected charge in the boundary layer and in the upper plume region, and strong turbulent mixing was observed throughout the atmosphere’s lowest 4 km. The clear slot region, through which particles sedimented, was anomalously dry compared with modelled values, with water clouds forming intermittently in the air beneath. Electrical aspects of dust should be included in numerical models, particularly the charge-related effects on cloud microphysical properties, to accurately represent particle behaviour and transport

MARIMO cells harbor a CALR mutation but are not dependent on JAK2/STAT5 signaling.

Work in the Green lab is supported by Leukemia and Lymphoma Research, Cancer Research UK, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre, and the Leukemia and Lymphoma Society of America. WW is supported by the Austrian Science Foundation (J 3578-B21). JN is supported by a Kay Kendall Leukaemia Clinical Fellowship.This is the final published version. It first appeared at http://www.nature.com/leu/journal/vaop/ncurrent/full/leu2014285a.html

Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts \u3c50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ( much or very much improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia

Changes in quality of life and disease-related symptoms in patients with polycythemia vera receiving ruxolitinib or standard therapy

Objectives Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant. Methods In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC). Results Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores. Conclusions Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant

Longitudinal cytokine profiling identifies GRO-α and EGF as potential biomarkers of disease progression in Essential Thrombocythemia

Myeloproliferative neoplasms (MPNs) are characterized by deregulation of mature blood cell production and increased risk of myelofibrosis (MF) and leukemic transformation. Numerous driver mutations have been identified but substantial disease heterogeneity remains unexplained, implying the involvement of additional as yet unidentified factors. The inflammatory microenvironment has recently attracted attention as a crucial factor in MPN biology, in particular whether inflammatory cytokines and chemokines contribute to disease establishment or progression. Here we present a large-scale study of serum cytokine profiles in more than 400 MPN patients and identify an essential thrombocythemia (ET)-specific inflammatory cytokine signature consisting of Eotaxin, GRO-α, and EGF. Levels of 2 of these markers (GRO-α and EGF) in ET patients were associated with disease transformation in initial sample collection (GRO-α) or longitudinal sampling (EGF). In ET patients with extensive genomic profiling data (n = 183) cytokine levels added significant prognostic value for predicting transformation from ET to MF. Furthermore, CD56+CD14+ pro-inflammatory monocytes were identified as a novel source of increased GRO-α levels. These data implicate the immune cell microenvironment as a significant player in ET disease evolution and illustrate the utility of cytokines as potential biomarkers for reaching beyond genomic classification for disease stratification and monitoring.The serum cytokine studies were supported by a research grant from the Rosetrees Trust. NFØ was supported by grants from the Danish Lundbeck Foundation and Danish Cancer Society, J.G. was supported by fellowships from Bloodwise and the Kay Kendall Leukaemia Fund; and M.S.S. is the recipient of a Biotechnology and Biological Sciences Research Council Industrial Collaborative Awards in Science and Engineering PhD Studentship. Work in the R.C.S. laboratory was supported by grants from the Stiftung Blutspendezentrum SRK beider Basel, the Swiss National Science Foundation (31003A-147016/1 and 31003A_166613), and the Swiss Cancer League (KLS-2950-02-2012 and KFS-3655-02-2015). A.K. was supported by the Else Kröner-Fresenius Foundation. Work in the A.R.G. laboratory is supported by the Wellcome Trust, Bloodwise, Cancer Research UK, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America. Work in the D.G.K. laboratory is supported by a Bloodwise Bennett Fellowship (15008), a European Hematology Association Non-Clinical Advanced Research Fellowship, and an ERC Starting Grant (ERC-2016-STG–715371). D.G.K. and A.R.G. are supported by a core support grant from the Wellcome Trust and Medical Research Council to the Wellcome MRC Cambridge Stem Cell Institute, the National Institute for Health Research Cambridge Biomedical Research Centre, and the CRUK Cambridge Cancer Centre

Photo-identification confirms that humpback whales (Megaptera novaeangliae) from eastern Australia migrate past New Zealand but indicates low levels of interchange with breeding grounds of Oceania

Recent photo-identification and genetic studies have identified at least five discrete breeding populations in Australia and Oceania: western Australia (D), eastern Australia (E (i)), New Caledonia (E (ii)), Tonga (E (iii)), French Polynesia and the Cook Islands (F). Also evident are low levels of intermingling among breeding populations consistent with the degree of genetic differentiation. Photo-identification has confirmed linkages between Area V feeding areas and eastern Australia breeding grounds and one genotype match has been reported between Area V feeding areas and Oceania breeding grounds. Recent abundance estimates show strong increases in the eastern Australian population, and some recovery in the New Caledonia and Tonga populations, but with little evidence of recovery at other known Oceania breeding grounds or New Zealand. Studies to date have provided no conclusive evidence of the migratory destination of humpback whales passing through New Zealand waters en route between Antarctic feeding areas and tropical breeding grounds. Photo-identification comparisons were undertaken between humpback whale fluke catalogues from eastern Australia (EA, 1315), Oceania east (OE, 513), Oceania west (OW, 166) and New Zealand (NZ, 13). Five matches were found between OE/OW, four matches between OW/EA and three matches between NZ/EA. The data are used to investigate and discuss the migratory destination and breeding ground migratory terchange of humpback whales travelling through New Zealand waters. The data confirm that humpback whales with site fidelity to eastern Australia migrate past New Zealand including through the Cook Strait and Foveaux Strait