Comparative Effectiveness of Adalimumab vs Tofacitinib in Patients With Rheumatoid Arthritis in Australia.

Importance: There is a need for observational studies to supplement evidence from clinical trials, and the target trial emulation (TTE) framework can help avoid biases that can be introduced when treatments are compared crudely using observational data by applying design principles for randomized clinical trials. Adalimumab (ADA) and tofacitinib (TOF) were shown to be equivalent in patients with rheumatoid arthritis (RA) in a randomized clinical trial, but to our knowledge, these drugs have not been compared head-to-head using routinely collected clinical data and the TTE framework. Objective: To emulate a randomized clinical trial comparing ADA vs TOF in patients with RA who were new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Design, Setting, and Participants: This comparative effectiveness study emulating a randomized clinical trial of ADA vs TOF included Australian adults aged 18 years or older with RA in the Optimising Patient Outcomes in Australian Rheumatology (OPAL) data set. Patients were included if they initiated ADA or TOF between October 1, 2015, and April 1, 2021; were new b/tsDMARD users; and had at least 1 component of the disease activity score in 28 joints using C-reactive protein (DAS28-CRP) recorded at baseline or during follow-up. Intervention: Treatment with either ADA (40 mg every 14 days) or TOF (10 mg daily). Main Outcomes and Measures: The main outcome was the estimated average treatment effect, defined as the difference in mean DAS28-CRP among patients receiving TOF compared with those receiving ADA at 3 and 9 months after initiating treatment. Missing DAS28-CRP data were multiply imputed. Stable balancing weights were used to account for nonrandomized treatment assignment. Results: A total of 842 patients were identified, including 569 treated with ADA (387 [68.0%] female; median age, 56 years [IQR, 47-66 years]) and 273 treated with TOF (201 [73.6%] female; median age, 59 years [IQR, 51-68 years]). After applying stable balancing weights, mean DAS28-CRP in the ADA group was 5.3 (95% CI, 5.2-5.4) at baseline, 2.6 (95% CI, 2.5-2.7) at 3 months, and 2.3 (95% CI, 2.2-2.4) at 9 months; in the TOF group, it was 5.3 (95% CI, 5.2-5.4) at baseline, 2.4 (95% CI, 2.2-2.5) at 3 months, and 2.3 (95% CI, 2.1-2.4) at 9 months. The estimated average treatment effect was -0.2 (95% CI, -0.4 to -0.03; P = .02) at 3 months and -0.03 (95% CI, -0.2 to 0.1; P = .60) at 9 months. Conclusions and Relevance: In this study, there was a modest but statistically significant reduction in DAS28-CRP at 3 months for patients receiving TOF compared with those receiving ADA and no difference between treatment groups at 9 months. Three months of treatment with either drug led to clinically relevant average reductions in mean DAS28-CRP, consistent with remission.

At the limits of "capability": The sexual and reproductive health of women migrant workers in Malaysia.

Despite the centrality of sexual and reproductive health (SRH) to UN Sustainable Development Goals (SDGs), women migrant workers in Malaysia face an environment inimical to their SRH needs. Drawing on qualitative case study material, we present the first empirical application of the capability approach (CA) to explore the reproductive health needs of women migrant workers in a developing country, offering an original analysis of the capability for SRH of these women. Specifically, we explore the resources available to them; their opportunities and freedoms ("capabilities"); and factors that mediate transformation of resources into capability sets ("conversion factors"). While SRH information and health care are notionally available, women migrant workers face multiple challenges in converting resources into functionings, constraining the achievement of capability for SRH. Challenges include language barriers, personal beliefs, power relations between workers and employers and the consequences of current migration policy. We consider the scale of the challenges facing these women in securing SRH rights, the difficulties of operationalising the CA within such a setting, and the implications of our findings for the adequacy of the CA in supporting marginalised populations.

Comparison of cone bioassay estimates at two laboratories with different Anopheles mosquitoes for quality assurance of pyrethroid insecticide-treated nets.

BACKGROUND: Quality assurance (QA) of insecticide-treated nets (ITNs) delivered to malaria-endemic countries is conducted by measuring physiochemical parameters, but not bioefficacy against malaria mosquitoes. This study explored utility of cone bioassays for pre-delivery QA of pyrethroid ITNs to test the assumption that cone bioassays are consistent across locations, mosquito strains, and laboratories. METHODS: Double-blinded bioassays were conducted on twenty unused pyrethroid ITNs of 4 brands (100 nets, 5 subsamples per net) that had been delivered for mass distribution in Papua New Guinea (PNG) having passed predelivery inspections. Cone bioassays were performed on the same net pieces following World Health Organization (WHO) guidelines at the PNG Institute of Medical Research (PNGIMR) using pyrethroid susceptible Anopheles farauti sensu stricto (s.s.) and at Ifakara Health Institute (IHI), Tanzania using pyrethroid susceptible Anopheles gambiae s.s. Additionally, WHO tunnel tests were conducted at IHI on ITNs that did not meet cone bioefficacy thresholds. Results from IHI and PNGIMR were compared using Spearman's Rank correlation, Bland-Altman (BA) analysis and analysis of agreement. Literature review on the use of cone bioassays for unused pyrethroid ITNs testing was conducted. RESULTS: In cone bioassays, 13/20 nets (65%) at IHI and 8/20 (40%) at PNGIMR met WHO bioefficacy criteria. All nets met WHO bioefficacy criteria on combined cone/tunnel tests at IHI. Results from IHI and PNGIMR correlated on 60-min knockdown (KD60) (rs = 0.6,p = 0.002,n = 20) and 24-h mortality (M24) (rs = 0.9,p < 0.0001,n = 20) but BA showed systematic bias between the results. Of the 5 nets with discrepant result between IHI and PNGIMR, three had confidence intervals overlapping the 80% mortality threshold, with averages within 1-3% of the threshold. Including these as a pass, the agreement between the results to predict ITN failure was good with kappa = 0.79 (0.53-1.00) and 90% accuracy. CONCLUSIONS: Based on these study findings, the WHO cone bioassay is a reproducible bioassay for ITNs with > 80% M24, and for all ITNs provided inherent stochastic variation and systematic bias are accounted for. The literature review confirms that WHO cone bioassay bioefficacy criteria have been previously achieved by all pyrethroid ITNs (unwashed), without the need for additional tunnel tests. The 80% M24 threshold remains the most reliable indicator of pyrethroid ITN quality using pyrethroid susceptible mosquitoes. In the absence of alternative tests, cone bioassays could be used as part of pre-delivery QA.

Stratification of malaria incidence in Papua New Guinea (2011-2019): Contribution towards a sub-national control policy.

Malaria risk in Papua New Guinea (PNG) is highly heterogeneous, between and within geographical regions, which is operationally challenging for control. To enhance targeting of malaria interventions in PNG, we investigated risk factors and stratified malaria incidence at the level of health facility catchment areas. Catchment areas and populations of 808 health facilities were delineated using a travel-time accessibility approach and linked to reported malaria cases (2011-2019). Zonal statistics tools were used to calculate average altitude and air temperature in catchment areas before they were spatially joined with incidence rates. In addition, empirical Bayesian kriging (EBK) was employed to interpolate incidence risk strata across PNG. Malaria annual incidence rates are, on average, 186.3 per 1000 population in catchment areas up to 600 m, dropped to 98.8 at (800-1400) m, and to 24.1 cases above 1400 m altitude. In areas above the two altitudinal thresholds 600m and 1400m, the average annual temperature drops below 22°C and 17°C, respectively. EBK models show very low- to low-risk strata (<100 cases per 1000) in the Highlands, National Capital District and Bougainville. In contrast, patches of high-risk (>200 per 1000) strata are modelled mainly in Momase and Islands Regions. Besides, strata with moderate risk (100-200) predominate throughout the coastal areas. While 35.7% of the PNG population (estimated 3.33 million in 2019) lives in places at high or moderate risk of malaria, 52.2% (estimated 4.88 million) resides in very low-risk areas. In five provinces, relatively large proportions of populations (> 50%) inhabit high-risk areas: New Ireland, East and West New Britain, Sandaun and Milne Bay. Incidence maps show a contrast in malaria risk between coastal and inland areas influenced by altitude. However, the risk is highly variable in low-lying areas. Malaria interventions should be guided by sub-national risk levels in PNG.

Insights into the potential of rheological measurements in development of dry powder inhalation formulations.

Study of flow is a key to development of dry powder inhalation formulations. Various static (bulk) and dynamic rheological measurements are used to study different aspects of powder flow and packing. Among rheological measurements, the permeability and the fluidization energy are, conceptually, most relevant to dispersion of dry powder inhalation formulations. The aim of the current study was to test the robustness and the range of applications of the two measurements, among other rheological measurements. To this end, we prepared and studied a series of ternary, carrier-based dry powder inhalation formulations. The formulations were mixtures of coarse-fine excipient (α-lactose monohydrate) blends, with different fine excipient concentrations (0.0-15.0 % w/w), and a spray-dried drug (fluticasone propionate) material. The excipient blends were characterized in terms of morphology, size, crystallinity, and rheological properties. The formulations were evaluated in vitro using a low resistance inhalation device, the Cyclohaler®, and a high resistance inhalation device, the Handihaler®. The study design aimed to complement literature data. Bulk rheological measurements, specifically the bulk density, the compressibility, and the permeability, exhibited satisfactory precision and could demonstrate changes in powder composition and structure. They hold a potential for use as critical material attributes to aid monitoring and optimization of carrier-based dry powder inhalation formulations in quality-by-design systems. On the other hand, dynamic rheological measurements, specifically the basic flowability energy, the specific energy, and the fluidization energy, generally exhibited high variability, which obscured interpretation of the measurements and implied heterogeneous powder structures. The fluidization energy could, nevertheless, convey structural changes taking place during powder fluidization.

A novel electronic patient-reported outcome delivery system to implement health-related quality of life measures in routine clinical care: An analysis of 5 years of experience.

Objective: To develop a simple and secure technological solution to incorporate electronic patient-reported outcomes (ePROs) into routine clinical care. Methods: A novel ePRO questionnaire delivery system was developed by Software for Specialists (S4S) in partnership with OPAL Rheumatology Australia. Validated questionnaires were sent from the electronic medical record (EMR) (Audit4) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), lupus or giant cell arteritis (GCA) and delivered to the patient's email address or completed in the clinic waiting room using a smart device (in-practice). Completed questionnaires were encrypted and returned to the patient's Audit4. Deidentified clinical data was extracted and aggregated across all sites. Data collected between April 2016-Dec 2020 were analysed descriptively. Results: Between April 2016 to Dec 2020, 221,352 Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), Patient Health Questionnaire-2 (PHQ-2) and/or HealthCare Resource Utilization (HCRU) questionnaires were sent from 39 of 42 contributing clinics (93%). 85% of questionnaires were delivered via email and 15% in-practice. Overall, 85% of patients completed at least one questionnaire, and of all questionnaires sent, 73% were completed. Females were more likely to engage with the questionnaires than males (87% vs. 81%), and older patients were slightly more likely to complete all questionnaires delivered. Conclusions: The novel Audit4 ePRO delivery system is an effective tool for incorporating PROs into routine clinical care. The data generated provides a unique opportunity to understand the full burden of disease for patients in the real-world setting and the impact of interventions.

Decreased bioefficacy of long-lasting insecticidal nets and the resurgence of malaria in Papua New Guinea.

Papua New Guinea (PNG) has the highest malaria transmission outside of Africa. Long-lasting insecticidal nets (LLINs) are believed to have helped to reduce average malaria prevalence in PNG from 16% in 2008 to 1% in 2014. Since 2015 malaria in PNG has resurged significantly. Here, we present observations documenting decreased bioefficacy of unused LLINs with manufacturing dates between 2013 and 2019 collected from villages and LLIN distributors in PNG. Specifically, we show that of n = 167 tested LLINs manufactured after 2013, only 17% are fulfilling the required World Health Organisation bioefficacy standards of ≥ 80% 24 h mortality or ≥ 95% 60 min knockdown in bioassays with pyrethroid susceptible Anopheles farauti mosquitoes. In contrast, all (100%, n = 25) LLINs with manufacturing dates prior to 2013 are meeting these bioefficacy standards. These results suggest that decreased bioefficacy of LLINs is contributing to the malaria resurgence in PNG and increased scrutiny of LLIN quality is warranted.

Mathematical modelling of the impact of expanding levels of malaria control interventions on Plasmodium vivax.

Plasmodium vivax poses unique challenges for malaria control and elimination, notably the potential for relapses to maintain transmission in the face of drug-based treatment and vector control strategies. We developed an individual-based mathematical model of P. vivax transmission calibrated to epidemiological data from Papua New Guinea (PNG). In many settings in PNG, increasing bed net coverage is predicted to reduce transmission to less than 0.1% prevalence by light microscopy, however there is substantial risk of rebounds in transmission if interventions are removed prematurely. In several high transmission settings, model simulations predict that combinations of existing interventions are not sufficient to interrupt P. vivax transmission. This analysis highlights the potential options for the future of P. vivax control: maintaining existing public health gains by keeping transmission suppressed through indefinite distribution of interventions; or continued development of strategies based on existing and new interventions to push for further reduction and towards elimination.

Low density, good flowability cyclodextrin-raffinose binary carrier for dry powder inhaler: anti-hygroscopicity and aerosolization performance enhancement.

BACKGROUND: The hygroscopicity of raffinose carrier for dry powder inhaler (DPI) was the main obstacle for its further application. Hygroscopicity-induced agglomeration would cause deterioration of aerosolization performance of raffinose, undermining the delivery efficiency. METHODS: Cyclodextrin-raffinose binary carriers (CRBCs) were produced by spray-drying so as to surmount the above issue. Physicochemical attributes and formation mechanism of CRBCs were explored in detail. The flow property of CRBCs was examined by FT4 Powder Rheometer. Hygroscopicity of CRBCs was elucidated by dynamic vapor sorption study. Aerosolization performance was evaluated by in vitro deposition profile and in vivo pharmacokinetic profile of CRBC based DPI formulations. RESULTS: The optimal formulation of CRBC (R4) was proven to possess anti-hygroscopicity and aerosolization performance enhancement properties. Concisely, the moisture uptake of R4 was c.a. 5% which was far lower than spray-dried raffinose (R0, c.a. 65%). R4 exhibited a high fine particle fraction value of 70.56 ± 0.61% and it was 3.75-fold against R0. The pulmonary and plasmatic bioavailability of R4 were significantly higher than R0 (p < 0.05). CONCLUSION: CRBC with anti-hygroscopicity and aerosolization performance enhancement properties was a promising approach for pulmonary drug delivery, which could provide new possibilities to the application of hygroscopic carriers for DPI.

The Effects of Relative Humidity on the Flowability and Dispersion Performance of Lactose Mixtures.

The flowability and dispersion behavior are two important physicochemical properties of pharmaceutical formulations for dry powder inhalers (DPIs). They are usually affected by the environmental conditions, such as temperature and relative humidity (RH). However, very few studies have been focused on the relationship between the two properties and their dependence on RH during storage. In this research, model pharmaceutical formulations were prepared using mixtures of coarse and fine lactose. The fractions of fines in the mixtures were 0%, 5%, 10%, and 20%, respectively. These blends were stored at four different RH levels, 0%, 30%, 58%, and 85%, for 48 h. The FT4 Powder Rheometer was used to evaluate the powder flowability, and the Malvern Spraytec® laser diffraction system was employed to assess the powder dispersion performance. The results indicated that both the flow and dispersion properties of lactose blends deteriorate after being stored at 85% RH, but improved after being conditioned at 58% RH. The fine particle fractions (FPFs) of the blends with 5% and 10% fine fractions and the as-received coarse lactose decreased when they were conditioned at 30% RH. For the blend with 20% fine fraction, a high RH during storage (i.e., 85% RH) affected the dispersion property, but had a limited influence on its flowability, while, for the coarse lactose powder, the different RH conditions affected its flowability, but not the dispersion results. A strong correlation between the powder flowability and its dispersion performance was found.

Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer.

Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulation's resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing.

Enacting corporate governance of healthcare safety and quality: a dramaturgy of hospital boards in England.

The governance of patient safety is a challenging concern for all health systems. Yet, while the role of executive boards receives increased scrutiny, the area remains theoretically and methodologically underdeveloped. Specifically, we lack a detailed understanding of the performative aspects at play: what board members say and do to discharge their accountabilities for patient safety. This article draws on qualitative data from overt non-participant observation of four NHS hospital Foundation Trust boards in England. Applying a dramaturgical framework to explore scripting, setting, staging and performance, we found important differences between case study sites in the performative dimensions of processing and interpretation of infection control data. We detail the practices associated with these differences--the legitimation of current performance, the querying of data classification, and the naming and shaming of executives--to consider their implications.

The Application of Modern Powder Characterisation Methods in Product and Process Development of Solid Dosage Forms.

The pharmaceutical industry still produces the vast majority of their products, from powdered ingredients, in the form of solid doses. Despite their ubiquity, powders are difficult materials to characterise and understand, as evidenced by the frequent problems encountered during manufacture. The reason for this is their complex rheological behaviour coupled with numerous environmental variations, such as humidity. Equally, the range of processes used to manipulate powders subject them to extremes of stress from high compaction loads seen in compactors to the dispersed state seen in fluidised bed dryers. Thus, it is evident that ensuring that the powders characteristics are compatible with the way they are to be processed is a clear prerequisite for today's Quality by Design driven manufacturing. Modern, computer controlled instrumental techniques, including the dynamic, bulk and shear property measurements have enabled direct measurements of a powders response to aeration, consolidation and flow rate - all at low stresses - as well as quantifying shear and bulk properties (such as density, compressibility and permeability). In order to demonstrate how fully characterising a powder can be used in the design, operation and troubleshooting of processes, this paper will present examples of common pharmaceutical unit operations and the different powder characteristics that most influence the performance of each.

Hospital board oversight of quality and safety: a stakeholder analysis exploring the role of trust and intelligence.

BACKGROUND: Hospital boards, those executive members charged with developing appropriate organisational strategies and cultures, have an important role to play in safeguarding the care provided by their organisation. However, recent concerns have been raised over boards' ability to enact their duty to ensure the quality and safety of care. This paper offers critical reflection on the relationship between hospital board oversight and patient safety. In doing so it highlights new perspectives and suggestions for developing this area of study. METHODS: The article draws on 10 interviews with key informants and policy actors who form part of the 'issue network' interested in the promotion of patient safety in the English National Health Service. RESULTS: The interviews surfaced a series of narratives regarding hospital board oversight of patient safety. These elaborated on the role of trust and intelligence in highlighting the potential dangers and limitations of approaches to hospital board oversight which have been narrowly focused on a risk-based view of organisational performance. In response, a need to engage with the development of trust based organisational relationships is identified, in which effective board oversight is built on 'trust' characterised by styles of leadership and behaviours that are attentive to the needs and concerns of both staff and patients. Effective board oversight also requires the gathering and triangulating of 'intelligence' generated from both national and local information sources. CONCLUSIONS: We call for a re-imagination of hospital board oversight in the light of these different perspectives and articulate an emerging research agenda in this area.

Overseeing oversight: governance of quality and safety by hospital boards in the English NHS.

OBJECTIVES: To contribute towards an understanding of hospital board composition and to explore board oversight of patient safety and health care quality in the English NHS. METHODS: We reviewed the theory related to hospital board governance and undertook two national surveys about board management in NHS acute and specialist hospital trusts in England. The first survey was issued to 150 trusts in 2011/2012 and was completed online via a dedicated web tool. A total 145 replies were received (97% response rate). The second online survey was undertaken in 2012/2013 and targeted individual board members, using a previously validated standard instrument on board members' attitudes and competencies (the Board Self-Assessment Questionnaire). A total of 334 responses were received from 165 executive and 169 non-executive board members, providing at least one response from 95 of the 144 NHS trusts then in existence (66% response rate). RESULTS: Over 90% of the English NHS trust boards had 10-15 members. We found no significant difference in board size between trusts of different types (e.g. Foundation Trusts versus non-Foundation Trusts and Teaching Hospital Trusts versus non-Teaching Hospital Trusts). Clinical representation on boards was limited: around 62% had three or fewer members with clinical backgrounds. For about two-thirds of the trusts (63%), board members with a clinical background comprised less than 30% of the members. Boards were using a wide range and mix of quantitative performance metrics and soft intelligence (e.g. walk-arounds, patient stories) to monitor their organisations with regard to patient safety. The Board Self-Assessment Questionnaire data showed generally high or very high levels of agreement with desirable statements of practice in each of its six dimensions. Aggregate levels of agreement within each dimension ranged from 73% (for the dimension addressing interpersonal issues) to 85% (on the political). CONCLUSIONS: English NHS boards largely hold a wide range of attitudes and behaviours that might be expected to benefit patient safety and quality. However, there is significant scope for improvement as regards formal training for board members on quality and safety, routine morbidity reporting at boards and attention to the interpersonal dynamics within boards. Directors with clinical backgrounds remain a minority on most boards despite policies to increase their representation. A better understanding of board composition, actions and attitudes should help refine policy recommendations around boards.

Hospital board oversight of quality and patient safety: a narrative review and synthesis of recent empirical research.

CONTEXT: Recurring problems with patient safety have led to a growing interest in helping hospitals' governing bodies provide more effective oversight of the quality and safety of their services. National directives and initiatives emphasize the importance of action by boards, but the empirical basis for informing effective hospital board oversight has yet to receive full and careful review. METHODS: This article presents a narrative review of empirical research to inform the debate about hospital boards' oversight of quality and patient safety. A systematic and comprehensive search identified 122 papers for detailed review. Much of the empirical work appeared in the last ten years, is from the United States, and employs cross-sectional survey methods. FINDINGS: Recent empirical studies linking board composition and processes with patient outcomes have found clear differences between high- and low-performing hospitals, highlighting the importance of strong and committed leadership that prioritizes quality and safety and sets clear and measurable goals for improvement. Effective oversight is also associated with well-informed and skilled board members. External factors (such as regulatory regimes and the publication of performance data) might also have a role in influencing boards, but detailed empirical work on these is scant. CONCLUSIONS: Health policy debates recognize the important role of hospital boards in overseeing patient quality and safety, and a growing body of empirical research has sought to elucidate that role. This review finds a number of areas of guidance that have some empirical support, but it also exposes the relatively inchoate nature of the field. Greater theoretical and methodological development is required if we are to secure more evidence-informed governance systems and practices that can contribute to safer care.

Comparing the content of leadership theories and managers' shared perceptions of effective leadership: a Q-method study of trainee managers in the English NHS.

Health service managers face potential conflicts between corporate and professional agendas, a tension sharpened for trainees by their junior status and relative inexperience. While academic leadership theory forms an integral part of contemporary management development programmes, relatively little is known of trainees' patterned subjectivities in relation to leadership theories. The objective of this study was to explore such subjectivities within a cohort of trainees on the National Health Service Graduate Management Training Scheme (NHS GMTS), a 'fast-track' programme which prepares graduate entrants for director-level health service management posts. A Q-method design was used and four shared subjectivities were identified: leadership as collaborative social process ('relational'); leadership as integrity ('moral'); leadership as effective support of subordinates ('team'); and leadership as construction of a credible leadership persona ('identity'). While the factors broadly map onto competencies indicated within the NHS Leadership Qualities Framework which underpin assessments of performance for this student group, it is important not to overstate the governance effect of the assessment regime. Rather, factors reflect tensions between required competencies, namely the mobilisation of diverse interest groups, the ethical base of decisions and the identity work required to convince others of leadership status. Indeed, factor 2 ('moral') effectively defines leadership as the embodiment of public service ethos.

Structures and processes for priority-setting by health-care funders: a national survey of primary care trusts in England.

Although explicit priority-setting is advocated in the health services literature and supported by the policies of many governments, relatively little is known about the extent and ways in which this is carried out at local decision-making levels. Our objective was to undertake a survey of local resource allocaters in the English National Health Services in order to map and explore current priority-setting activity. A national survey was sent to Directors of Commissioning in English Primary Care Trusts (PCTs). The survey was designed to provide a picture of the types of priority-setting activities and techniques that are in place and offer some assessment of their perceived effectiveness. There is variation in the scale, aims and methods of priority-setting functions across PCTs. A perceived strength of priority-setting processes is in relation to the use of particular tools and/or development of formal processes that are felt to increase transparency. Perceived weaknesses tended to lie in the inability to sufficiently engage with a range of stakeholders. Although a number of formal priority-setting processes have been developed, there are a series of remaining challenges such as ensuring priority-setting goes beyond the margins and is embedded in budget management, and the development of disinvestment as well as investment strategies. Furthermore, if we are genuinely interested in a more explicit approach to priority-setting, then fostering a more inclusive and transparent process will be required.

Priority-setting and rationing in healthcare: evidence from the English experience.

In a context of ever increasing demand, the recent economic downturn has placed further pressure on decision-makers to effectively target healthcare resources. Over recent years there has been a push to develop more explicit evidence-based priority-setting processes, which aim to be transparent and inclusive in their approach and a number of analytical tools and sources of evidence have been developed and utilised at national and local levels. This paper reports findings from a qualitative research study which investigated local priority-setting activity across five English Primary Care Trusts, between March and November 2012. Findings demonstrate the dual aims of local decision-making processes: to improve the overall effectiveness of priority-setting (i.e. reaching 'correct' resource allocation decisions); and to increase the acceptability of priority-setting processes for those involved in both decision-making and implementation. Respondents considered priority-setting processes to be compartmentalised and peripheral to resource planning and allocation. Further progress was required with regard to disinvestment and service redesign with respondents noting difficulty in implementing decisions. While local priority-setters had begun to develop more explicit processes, public awareness and input remained limited. The leadership behaviours required to navigate the political complexities of working within and across organisations with differing incentives systems and cultures remained similarly underdeveloped.

SaTScan on a Cloud: On-Demand Large Scale Spatial Analysis of Epidemics.

By using cloud computing it is possible to provide on- demand resources for epidemic analysis using computer intensive applications like SaTScan. Using 15 virtual machines (VM) on the Nimbus cloud we were able to reduce the total execution time for the same ensemble run from 8896 seconds in a single machine to 842 seconds in the cloud. Using the caBIG tools and our iterative software development methodology the time required to complete the implementation of the SaTScan cloud system took approximately 200 man-hours, which represents an effort that can be secured within the resources available at State Health Departments. The approach proposed here is technically advantageous and practically possible.