Dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia.

BRAF V600E is the key oncogenic driver mutation in hairy cell leukemia (HCL). We report the efficacy and safety of dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive HCL. This open-label, phase 2 study enrolled patients with BRAF V600E mutation-positive HCL refractory to first-line treatment with a purine analog or relapsed after ≥2 prior lines of treatment. Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed objective response rate (ORR) per criteria adapted from National Comprehensive Cancer Network-Consensus Resolution guidelines. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Fifty-five patients with BRAF V600E mutation-positive HCL were enrolled. The investigator-assessed ORR was 89.0% (95% confidence interval, 77.8%-95.9%); 65.5% of patients had a complete response (without minimal residual disease [MRD]: 9.1% [negative immunohistochemistry of bone marrow {BM} biopsy], 12.7% [negative BM aspirate flow cytometry {FC}], 16.4% [negative immunohistochemistry and/or FC results]; with MRD, 49.1%), and 23.6% had a partial response. The 24-month DOR was 97.7% with 24-month PFS and OS rates of 94.4% and 94.5%, respectively. The most common treatment-related adverse events were pyrexia (58.2%), chills (47.3%), and hyperglycemia (40.0%). Dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile consistent with previous observations in other indications and should be considered as a rituximab-free therapeutic option for patients with relapsed/refractory BRAF V600E mutation-positive HCL. This trial is registered at www.clinicaltrials.gov as #NCT02034110.

Remoteness, models of primary care and inequity: Medicare under-expenditure in the Northern Territory.

Objective To analyse Medicare expenditure by State/Territory, remoteness, and Indigenous demography to assess funding equality in meeting the health needs of remote Indigenous populations in the Northern Territory. Methods Analytic descriptions of Medicare online reports on services and benefits by key demographic variables linked with Australian Bureau of Statistics data on remoteness and Indigenous population proportion. The Northern Territory Indigenous and non-Indigenous populations were compared with the Australian average between the 2010/2011 and 2019/2020 fiscal years in terms of standardised rates of Medicare services and benefits. These were further analysed using ordinary least squares, simultaneous equations and multilevel models. Results In per capita terms, the Northern Territory receives around 30% less Medicare funds than the national average, even when additional Commonwealth funding for Aboriginal medical services is included. This funding shortfall amounts to approximately AU$80 million annually across both the Medicare Benefits Schedule and Pharmaceutical Benefits Scheme. The multilevel models indicate that providing healthcare for an Aboriginal and Torres Strait Islander person in a remote area involves a Medicare shortfall of AU$531-AU$1041 less Medicare Benefits Schedule benefits per annum compared with a non-Indigenous person in an urban area. Indigenous population proportion, together with remoteness, explained 51% of the funding variation. An age-sex based capitation funding model would correct about 87% of the Northern Territory primary care funding inequality. Conclusions The current Medicare funding scheme systematically disadvantages the Northern Territory. A needs-based funding model is required that does not penalise the Northern Territory population based on the remote primary health care service model.

Realising the potential of health needs assessments.

Population-level assessment and planning has traditionally been the role of public health departments but in establishing Primary Health Networks (PHNs), the Australian Government has instituted a new mechanism for identifying community needs and commissioning services to meet those needs. If PHNs are to achieve the vision of nimble organisations capable of identifying and addressing local health needs via integrated health and social services, several things need to occur. First, PHN funding schedules must become more flexible. Second, the Federal health department must maintain an open dialogue with PHNs, permit waivers in funding schedules to suit local conditions and be prepared to back innovations with seed investment. Third, health data exchange and linkage must be accelerated to better inform community needs assessments and commissioning. Finally, PHNs must be encouraged and supported to develop collaborations both within and outside the health sector in order to identify and address a broad set of health issues and determinants. By following these principles, PHNs may become leading change agents in the Australian healthcare system.

Impact of policy support on uptake of evidence-based continuous quality improvement activities and the quality of care for Indigenous Australians: a comparative case study.

OBJECTIVES: To examine the impact of state/territory policy support on (1) uptake of evidence-based continuous quality improvement (CQI) activities and (2) quality of care for Indigenous Australians. DESIGN: Mixed-method comparative case study methodology, drawing on quality-of-care audit data, documentary evidence of policies and strategies and the experience and insights of stakeholders involved in relevant CQI programmes. We use multilevel linear regression to analyse jurisdictional differences in quality of care. SETTING: Indigenous primary healthcare services across five states/territories of Australia. PARTICIPANTS: 175 Indigenous primary healthcare services. INTERVENTIONS: A range of national and state/territory policy and infrastructure initiatives to support CQI, including support for applied research. PRIMARY AND SECONDARY OUTCOME MEASURES: (i) Trends in the consistent uptake of evidence-based CQI tools available through a research-based CQI initiative (the Audit and Best Practice in Chronic Disease programme) and (ii) quality of care (as reflected in adherence to best practice guidelines). RESULTS: Progressive uptake of evidence-based CQI activities and steady improvements or maintenance of high-quality care occurred where there was long-term policy and infrastructure support for CQI. Where support was provided but not sustained there was a rapid rise and subsequent fall in relevant CQI activities. CONCLUSIONS: Health authorities should ensure consistent and sustained policy and infrastructure support for CQI to enable wide-scale and ongoing improvement in quality of care and, subsequently, health outcomes. It is not sufficient for improvement initiatives to rely on local service managers and clinicians, as their efforts are strongly mediated by higher system-level influences.

Managing declining yields from ageing tea plantations.

Strong growth in the demand for tea requires further increases in the productivity of plantations. Declining or stagnant yields are commonly observed in older plantations. Possible controlling factors for yield decline are reviewed including ageing of plants, chronic disease and sub-optimal soil conditions such as excess soil acidity and low soil organic matter. Management options for addressing these factors are evaluated, including replanting. A systematic approach to decision-making about replanting is presented. Practice for replanting is reviewed and it is concluded that evidence to support a general case for replanting is limited, unless based on the introduction of more productive clones and/or better plant spacing.