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1.  Using qualitative mixed methods to study small health care organizations while maximising trustworthiness and authenticity 
The primary health care sector delivers the majority of health care in western countries through small, community-based organizations. However, research into these healthcare organizations is limited by the time constraints and pressure facing them, and the concern by staff that research is peripheral to their work. We developed Q-RARA—Qualitative Rapid Appraisal, Rigorous Analysis—to study small, primary health care organizations in a way that is efficient, acceptable to participants and methodologically rigorous.
Q-RARA comprises a site visit, semi-structured interviews, structured and unstructured observations, photographs, floor plans, and social scanning data. Data were collected over the course of one day per site and the qualitative analysis was integrated and iterative.
We found Q-RARA to be acceptable to participants and effective in collecting data on organizational function in multiple sites without disrupting the practice, while maintaining a balance between speed and trustworthiness.
The Q-RARA approach is capable of providing a richly textured, rigorous understanding of the processes of the primary care practice while also allowing researchers to develop an organizational perspective. For these reasons the approach is recommended for use in small-scale organizations both within and outside the primary health care sector.
PMCID: PMC4245737  PMID: 25407663
Primary health care; Organizations; Qualitative research; Qualitative analysis; Mixed method research
2.  The Computerized Medical Record as a Tool for Clinical Governance in Australian Primary Care 
Computerized medical records (CMR) are used in most Australian general practices. Although CMRs have the capacity to amalgamate and provide data to the clinician about their standard of care, there is little research on the way in which they may be used to support clinical governance: the process of ensuring quality and accountability that incorporates the obligation that patients are treated according to best evidence.
The objective of this study was to explore the capability, capacity, and acceptability of CMRs to support clinical governance.
We conducted a realist review of the role of seven CMR systems in implementing clinical governance, developing a four-level maturity model for the CMR. We took Australian primary care as the context, CMR to be the mechanism, and looked at outcomes for individual patients, localities, and for the population in terms of known evidence-based surrogates or true outcome measures.
The lack of standardization of CMRs makes national and international benchmarking challenging. The use of the CMR was largely at level two of our maturity model, indicating a relatively simple system in which most of the process takes place outside of the CMR, and which has little capacity to support benchmarking, practice comparisons, and population-level activities. Although national standards for coding and projects for record access are proposed, they are not operationalized.
The current CMR systems can support clinical governance activities; however, unless the standardization and data quality issues are addressed, it will not be possible for current systems to work at higher levels.
PMCID: PMC3744386  PMID: 23939340
clinical governance; electronic health records; general practice; realist evaluation; quality assurance; health care
3.  Low Vitamin B12 Levels among Newly-Arrived Refugees from Bhutan, Iran and Afghanistan: A Multicentre Australian Study 
PLoS ONE  2013;8(2):e57998.
Vitamin B12 deficiency is prevalent in many countries of origin of refugees. Using a threshold of 5% above which a prevalence of low Vitamin B12 is indicative of a population health problem, we hypothesised that Vitamin B12 deficiency exceeds this threshold among newly-arrived refugees resettling in Australia, and is higher among women due to their increased risk of food insecurity. This paper reports Vitamin B12 levels in a large cohort of newly arrived refugees in five Australian states and territories.
In a cross-sectional descriptive study, we collected Vitamin B12, folate and haematological indices on all refugees (n = 916; response rate 94% of eligible population) who had been in Australia for less than one year, and attended one of the collaborating health services between July 2010 and July 2011.
16.5% of participants had Vitamin B12 deficiency (<150 pmol/L). One-third of participants from Iran and Bhutan, and one-quarter of participants from Afghanistan had Vitamin B12 deficiency. Contrary to our hypothesis, low Vitamin B12 levels were more prevalent in males than females. A higher prevalence of low Vitamin B12 was also reported in older age groups in some countries. The sensitivity of macrocytosis in detecting Vitamin B12 deficiency was only 4.6%.
Vitamin B12 deficiency is an important population health issue in newly-arrived refugees from many countries. All newly-arrived refugees should be tested for Vitamin B12 deficiency. Ongoing research should investigate causes, treatment, and ways to mitigate food insecurity, and the contribution of such measures to enhancing the health of the refugee communities.
PMCID: PMC3585239  PMID: 23469126
4.  Physical Basis of Metal-Binding Specificity in Escherichia coli NikR 
Journal of the American Chemical Society  2009;131(29):10220-10228.
In Escherichia coli and other bacteria, nickel uptake is regulated by the transcription factor NikR. Nickel binding at high-affinity sites in E. coli NikR (EcNikR) facilitates EcNikR binding to the nik operon, where it then suppresses transcription of genes encoding the nickel uptake transporter, NikABCDE. A structure of the EcNikR-DNA complex suggests that a second metal-binding site is also present when NikR binds to the nik operon. Moreover, this co-crystal structure raises the question of what metal occupies the second site under physiological conditions: K+, which is present in the crystal structure, or Ni2+, which has been proposed to bind to low- as well as high-affinity sites on EcNikR. To determine which ion is preferred at the second metal-binding site and the physical basis for any preference of one ion over another in both the second metal-binding site and the high-affinity sites, we conducted a series of detailed molecular simulations on the EcNikR structure. Simulations that place Ni2+ at high-affinity sites lead to stable trajectories with realistic ion–ligand distances and geometries, while simulations that place K+ at these sites lead to conformational changes in the protein that are likely unfavorable for ion binding. By contrast, simulations on the second metal site in the EcNikR-DNA complex lead to stable trajectories with realistic geometries regardless of whether K+ or Ni2+ occupies this site. Electrostatic binding free energy calculations, however, suggest that EcNikR binding to DNA is more favorable when the second metal-binding site contains K+. An analysis of the energetic contributions to the electrostatic binding free energy suggests that, while the interaction between EcNikR and DNA is more favorable when the second site contains Ni2+, the large desolvation penalty associated with moving Ni2+ from solution to the relatively buried second site offsets this favorable interaction term. Additional free energy simulations that account for both electrostatic and non-electrostatic effects argue that EcNikR binding to DNA is most favorable when the second site contains a monovalent ion the size of K+. Taken together, these data suggest that the EcNikR structure is most stable when Ni2+ occupies high-affinity sites and that EcNikR binding to DNA is more favorable when the second site contains K+.
PMCID: PMC3579654  PMID: 19621966
5.  A spatial analysis of the expanding roles of nurses in general practice 
BMC Nursing  2012;11:13.
Changes to the workforce and organisation of general practice are occurring rapidly in response to the Australian health care reform agenda, and the changing nature of the medical profession. In particular, the last five years has seen the rapid introduction and expansion of a nursing workforce in Australian general practices. This potentially creates pressures on current infrastructure in general practice.
This study used a mixed methods, ‘rapid appraisal’ approach involving observation, photographs, and interviews.
Nurses utilise space differently to GPs, and this is part of the diversity they bring to the general practice environment. At the same time their roles are partly shaped by the ways space is constructed in general practices.
The fluidity of nursing roles in general practice suggests that nurses require a versatile space in which to maximize their role and contribution to the general practice team.
PMCID: PMC3488547  PMID: 22870933
General practice; Private practice nursing; Physicians office; Spatial analysis; Skill mix
6.  Resilience among doctors who work in challenging areas: a qualitative study 
The British Journal of General Practice  2011;61(588):e404-e410.
Although physician burnout has received considerable attention, there is little research of doctors who thrive while working in challenging conditions.
To describe attitudes to work and job satisfaction among Australian primary care practitioners who have worked for more than 5 years in areas of social disadvantage.
Semi-structured interviews were conducted with 15 primary health care practitioners working in Aboriginal health, prisons, drug and alcohol medicine, or youth and refugee health. The interviews explored attitudes towards work and professional satisfaction, and strategies to promote resilience.
All doctors were motivated by the belief that helping a disadvantaged population is the ‘right thing’ to do. They were sustained by a deep appreciation and respect for the population they served, an intellectual engagement with the work itself, and the ability to control their own working hours (often by working part-time in the field of interest). In their clinical work, they recognised and celebrated small gains and were not overwhelmed by the larger context of social disadvantage.
If organisations want to increase the numbers of medical staff or increase the work commitment of staff in areas of social disadvantage, they should consider supporting doctors to work part-time, allowing experienced doctors to mentor them to model these patient-appreciative approaches, and reinforcing, for novice doctors, the personal and intellectual pleasures of working in these fields.
PMCID: PMC3123503  PMID: 21722448
burnout, professional; practitioner satisfaction; primary care; resilience, psychological; social disadvantage; vulnerable populations; work satisfaction
7.  The patient and the computer in the primary care consultation 
Studies of the doctor–patient relationship have focused on the elaboration of power and/or authority using a range of techniques to study the encounter between doctor and patient. The widespread adoption of computers by doctors brings a third party into the consultation. While there has been some research into the way doctors view and manage this new relationship, the behavior of patients in response to the computer is rarely studied. In this paper, the authors use Goffman's dramaturgy to explore patients' approaches to the doctor's computer in the consultation, and its influence on the patient–doctor relationship.
Observational study of Australian general practice. 141 consultations from 20 general practitioners were videotaped and analyzed using a hermeneutic framework.
Patients negotiated the relationship between themselves, the doctor, and the computer demonstrating two themes: dyadic (dealing primarily with the doctor) or triadic (dealing with both computer and doctor). Patients used three signaling behaviors in relation to the computer on the doctor's desk (screen watching, screen ignoring, and screen excluding) to influence the behavior of the doctor. Patients were able to draw the doctor to the computer, and used the computer to challenge doctor's statements.
This study demonstrates that in consultations where doctors use computers, the computer can legitimately be regarded as part of a triadic relationship. Routine use of computers in the consultation changes the doctor–patient relationship, and is altering the distribution of power and authority between doctor and patient.
PMCID: PMC3116262  PMID: 21262923
Physician patient relationship; medical informatics; qualitative research; office visits; computers; patient-centered medicine
8.  Patient Navigation to Increase Mammography Screening Among Inner City Women 
Lower mammography screening rates among minority and low income women contribute to increased morbidity and mortality from breast cancer.
To evaluate the effect of a patient navigation intervention on adherence rates to biennial screening mammography among women engaged in primary care at an inner-city academic medical center.
Quality improvement intervention with a concurrent control group, conducted from February to November of 2008.
Study Subjects
All women in a hospital-based primary care practice aged 51–70 years. Subjects were randomized at the level of their primary care provider, such that half of the patients in the practice received the intervention, while the other half received usual care.
Intervention subjects whose last mammogram was >18 months prior received a combination of telephone calls and reminder letters from patient navigators trained to identify barriers to care. Navigators were integrated into primary care teams and interacted directly with patients, providers, and radiology to coordinate care. Navigators utilized an electronic report to track subjects. Adherence rates to biennial mammography were assessed in intervention and control groups at baseline and post-intervention.
Key Results
A total of 3,895 women were randomized to intervention (n = 1,817) and control (n = 2,078) groups. Mean age was 60, 71% were racial/ethnic minorities, 23% were non-English speaking, and 63% had public or no health insurance. At baseline, there was no difference in mammography adherence between the control and intervention groups (78%, respectively, p = 0.55). After the 9-month intervention, mammogram adherence was higher in the intervention group compared with the control group (87% vs. 76%, respectively, p < 0.001). Except among Hispanic women who demonstrated high rates in both the intervention and control groups (85% and 83%, respectively), all racial/ethnic and insurance groups demonstrated higher adherence in the intervention group.
Patient navigation improves biennial mammography rates for inner city, low income, minority populations.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-010-1527-2) contains supplementary material, which is available to authorized users.
PMCID: PMC3019333  PMID: 20931294
mammography screening; patient navigation; quality improvement; disparities; women’s health
9.  MDM2 Polymorphism Increases Susceptibility to Childhood Acute Myeloid Leukemia: A Report from the Children’s Oncology Group 
Pediatric blood & cancer  2010;55(2):248-253.
The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li-Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have ten fold increase resistance to topoisomerase II inhibitors in vitro.
We genotyped children (n=575) with de novo acute myeloid leukemia (AML) treated on three Children’s Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population.
The variant G/G genotype was associated with an increased susceptibility to AML (OR 1.5; p=0.049). However, the presence of the variant allele at SNP309 did not modify disease response or toxicity in children treated on CCG protocols 2941/2961.
The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy.
PMCID: PMC2915901  PMID: 20582981
AML; MDM2; SNP 309; Children’s Oncology Group; susceptibility
10.  Following the funding trail: Financing, nurses and teamwork in Australian general practice 
Across the globe the emphasis on roles and responsibilities of primary care teams is under scrutiny. This paper begins with a review of general practice financing in Australia, and how nurses are currently funded. We then examine the influence on funding structures on the role of the nurse. We set out three dilemmas for policy-makers in this area: lack of an evidence base for incentives, possible untoward impacts on interdisciplinary functioning, and the substitution/enhancement debate.
This three year, multimethod study undertook rapid appraisal of 25 general practices and year-long studies in seven practices where a change was introduced to the role of the nurse. Data collected included interviews with nurses (n = 36), doctors (n = 24), and managers (n = 22), structured observation of the practice nurse (51 hours of observation), and detailed case studies of the change process in the seven year-long studies.
Despite specific fee-for-service funding being available, only 6% of nurse activities generated such a fee. Yet the influence of the funding was to focus nurse activity on areas that they perceived were peripheral to their roles within the practice.
Interprofessional relationships and organisational climate in general practices are highly influential in terms of nursing role and the ability of practices to respond to and utilise funding mechanisms. These factors need to be considered, and the development of optimal teamwork supported in the design and implementation of further initiatives that financially support nursing in general practice.
PMCID: PMC3050696  PMID: 21329506
11.  Synchrotron Protein Footprinting Supports Substrate Translocation by ClpA via ATP-Induced Movements of the D2 Loop 
Structure (London, England : 1993)  2008;16(8):1157-1165.
Synchrotron x-ray protein footprinting is used to study structural changes upon formation of the ClpA hexamer. Comparative solvent accessibilities between ClpA monomer and ClpA hexamer samples are in agreement throughout most of the sequence with calculations based on two previously proposed hexameric models. The data differ substantially from the proposed models in two parts of the structure: the D1 sensor 1 domain and the D2 loop region. The results suggest that these two regions can access alternate conformations in which their solvent protection is greater than in the structural models based on crystallographic data. In combination with previously reported structural data, the footprinting data provide support for a revised model in which the D2 loop contacts the D1 sensor 1 domain in the ATP-bound form of the complex. These data provide the first direct experimental support for the nucleotide-dependent D2 loop conformational change previously proposed to mediate substrate translocation.
PMCID: PMC2929679  PMID: 18682217
12.  Strengthening field-based training in low and middle-income countries to build public health capacity: Lessons from Australia's Master of Applied Epidemiology program 
The International Health Regulations (2005) and the emergence and global spread of infectious diseases have triggered a re-assessment of how rich countries should support capacity development for communicable disease control in low and medium income countries (LMIC). In LMIC, three types of public health training have been tried: the university-based model; streamed training for specialised workers; and field-based programs. The first has low rates of production and teaching may not always be based on the needs and priorities of the host country. The second model is efficient, but does not accord the workers sufficient status to enable them to impact on policy. The third has the most potential as a capacity development measure for LMIC, but in practice faces challenges which may limit its ability to promote capacity development.
We describe Australia's first Master of Applied Epidemiology (MAE) model (established in 1991), which uses field-based training to strengthen the control of communicable diseases. A central attribute of this model is the way it partners and complements health department initiatives to enhance workforce skills, health system performance and the evidence-base for policies, programs and practice.
The MAE experience throws light on ways Australia could collaborate in regional capacity development initiatives. Key needs are a shared vision for a regional approach to integrate training with initiatives that strengthen service and research, and the pooling of human, financial and technical resources. We focus on communicable diseases, but our findings and recommendations are generalisable to other areas of public health.
PMCID: PMC2672090  PMID: 19358710
13.  General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries 
PLoS ONE  2008;3(5):e2269.
Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada.
Methodology/Principal Findings
We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently.
This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research.
PMCID: PMC2386973  PMID: 18509538
14.  Medicine Goes to School: Teachers as Sickness Brokers for ADHD 
PLoS Medicine  2006;3(4):e182.
Christine Phillips explores the roles of teachers as brokers for ADHD and its treatment, and the strategies used by the pharmaceutical industry to frame educators' responses to ADHD.
PMCID: PMC1434504  PMID: 16597177
15.  Searching for the nik Operon: How a Ligand-Responsive Transcription Factor Hunts for Its DNA Binding Site† 
Biochemistry  2010;49(36):7757-7763.
Transcription factors regulate a wide variety of genes in the cell and play a crucial role in maintaining cellular homeostasis. A major unresolved issue is how transcription factors find their specific DNA binding sequence in the vast expanse of the cell and how they do so at rates that appear faster than the diffusion limit. Here, we relate an atomic-detail model that has been developed to describe the transcription factor NikR’s mechanism of DNA binding to the broader theories of how transcription factors find their binding sites on DNA. NikR is the nickel regulatory transcription factor for many bacteria, and NikR from Escherichia coli is one of the best studied ligand-mediated transcription factors. For the E. coli NikR protein, there is a wide variety of structural, biochemical, and computational studies that provide significant insight into the NikR−DNA binding mechanism. We find that the two models, the atomic-level model for E. coli NikR and the cellular model for transcription factors in general, are in agreement, and the details laid out by the NikR system may lend additional credence to the current models for transcription factors searching for DNA.
PMCID: PMC2934762  PMID: 20712334
16.  Structural Basis of Low-Affinity Nickel Binding to the Nickel-Responsive Transcription Factor NikR from Escherichia coli†‡ 
Biochemistry  2010;49(36):7830-7838.
Escherichia coli NikR regulates cellular nickel uptake by binding to the nik operon in the presence of nickel and blocking transcription of genes encoding the nickel uptake transporter. NikR has two binding affinities for the nik operon: a nanomolar dissociation constant with stoichiometric nickel and a picomolar dissociation constant with excess nickel [Bloom, S. L., and Zamble, D. B. (2004) Biochemistry 43, 10029−10038; Chivers, P. T., and Sauer, R. T. (2002) Chem. Biol. 9, 1141−1148]. While it is known that the stoichiometric nickel ions bind at the NikR tetrameric interface [Schreiter, E. R., et al. (2003) Nat. Struct. Biol. 10, 794−799; Schreiter, E. R., et al. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 13676−13681], the binding sites for excess nickel ions have not been fully described. Here we have determined the crystal structure of NikR in the presence of excess nickel to 2.6 Å resolution and have obtained nickel anomalous data (1.4845 Å) in the presence of excess nickel for both NikR alone and NikR cocrystallized with a 30-nucleotide piece of double-stranded DNA containing the nik operon. These anomalous data show that excess nickel ions do not bind to a single location on NikR but instead reveal a total of 22 possible low-affinity nickel sites on the NikR tetramer. These sites, for which there are six different types, are all on the surface of NikR, and most are found in both the NikR alone and NikR−DNA structures. Using a combination of crystallographic data and molecular dynamics simulations, the nickel sites can be described as preferring octahedral geometry, utilizing one to three protein ligands (typically histidine) and at least two water molecules.
PMCID: PMC2934763  PMID: 20704276

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