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Health Expectations : An International Journal of Public Participation in Health Care and Health Policy logoLink to Health Expectations : An International Journal of Public Participation in Health Care and Health Policy
. 2002 Aug 28;5(3):236–245. doi: 10.1046/j.1369-6513.2002.00183.x

Responding to the active and passive patient: flexibility is the key

Rhonda F Brown 1, Phyllis N Butow 1, Michael Henman 1, Stewart M Dunn 1, Francis Boyle 2, Martin HN Tattersall 3
PMCID: PMC5060149  PMID: 12199662

Abstract

Background  Patients vary widely in their preferences and capacity for participation in medical decision‐making. This study aimed to document oncologist responses to more extreme presentations and identify helpful and unhelpful strategies for clinicians.

Patients and methods  A trained actor played the role of a patient with early stage breast cancer who was attending her first consultation with a medical oncologist. She adopted in random order two different consultation participation styles: that of a very anxious, active patient, and that of a depressed, passive patient. Medical consultations between the actor and 16 medical oncologists were videotaped and then analysed qualitatively by two trained raters.

Results  Strategies that facilitated shared decision‐making with both patient types and were positively endorsed by the actor/patient included explicit agenda‐setting, active listening, checking understanding, endorsing question‐asking, offering decisional delay, and non‐verbal behaviours conveying empathy and warmth. Oncologists successfully negotiated with the active patient to share control of the consultation, and responded to emotional cues from the passive patient. Unhelpful strategies were also identified.

Conclusions  Few clinicians receive training in responding to differing communication styles in their patients that could potentially cause conflict and hinder optimal treatment decision‐making. This study suggests some useful strategies for oncologists to consider, to widen their behavioural repertoire in the cancer consultation.

Keywords: doctor–patient communication, shared decision‐making

Introduction

Many cancer patients today want detailed information about their cancer diagnosis, prognosis, and treatment options 1 , 2 and in recent years there has been an increased emphasis on involving patients in decision‐making. 3 , 4 Degner et al. 3 surveyed 1012 women with breast cancer. Twenty‐two per cent preferred to take the lead in decision‐making, 34% wanted to defer decision‐making to the clinician, and 44% preferred to share decision‐making with their doctor. While patient preferences for information and involvement in medical care are variable, there is evidence to suggest that outcomes are better if patients participate in medical decision‐making or believe they have control over their treatment decisions. 5 , 6 , 7 , 8 , 9 In a recent prospective study of more than 300 Australian cancer patients seeing an oncologist for the first time, 4 patients who reported having either shared in the treatment decision or who participated more than they had initially wished, were significantly more satisfied than those patients who were less involved in the decision‐making process. These results suggest that a policy of engaging patients and seeking their participation preferences in decision‐making about their medical care is preferable to a less participatory style.

However, few oncologists have received training in either responding to differing patient communication styles or encouraging patient participation in decision‐making. Indeed, some studies have indicated that doctors become uncomfortable if patients change their style from the more conventional passive role. For example, Roter 10 evaluated a short coaching session with a psychologist, which encouraged patients to ask questions in their general practice consultation. Although question‐asking increased after the coaching session, an unexpected outcome was an increased number of negative interchanges between the patient and doctor. This suggests that doctors were unsure of how to best respond to active patients, and may indeed have felt uncomfortable with this patient type.

On the other hand, patients who respond in a very passive manner, either because they prefer non‐involvement in decision‐making or because their energy has been sapped by the emotional onslaught of diagnosis, present their own challenge. How can the principle of informed consent be honoured if patients do not express a treatment preference? How can doctors facilitate patients' involvement in decision‐making when the patient is currently feeling overwhelmed? It is well documented that patient understanding is negatively influenced by emotional distress, 11 and that little information will be retained until emotional issues have been addressed. However, many doctors have expressed anxiety and lack of confidence in addressing patients' emotional issues. 12

In the past few years, there has been growing recognition of the complexity of communication tasks doctors face, especially in the light of changing patient expectations. This recognition has stimulated the development of communication skills training courses in medical schools and professional forums. In addition, clinical practice guidelines have recently been issued, such as the Psychosocial Clinical Practice Guidelines issued by the National Health and Medical Research Council in Australia 13 which detail the informational, support and counselling needs of women with breast cancer. These evidence‐based guidelines encourage doctors to use supportive communication skills in their interactions with patients, provide adequate information, elicit a patient's preferred role in treatment decision‐making and tailor the information to the needs and preferences of patients. However, practical information on how to achieve these aims is scarce.

Two papers have described a model of shared decision‐making which incorporate suggested doctor behaviours. 14 , 15 Towle and Godolphin 14 list eight steps in shared decision‐making, including establishing a partnership, reviewing patient preferences for information and involvement, and eliciting and responding to patients' concerns, values and expectations. Elwyn et al. 15 further refine Towle and Godolphins' model by translating it into specific competencies. Interestingly, in the latter study which analysed focus group discussions with registrars about shared decision‐making, the participants emphasized the need to be sensitive to ‘contextual’ modifiers such as age, educational achievement and anxiety. However, apart from noting the need to elicit and respect patient preferences for information and involvement, no specific strategies were presented to respond to patient diversity.

The focus of the present study was to document ways in which experienced medical oncologists' consultation behaviours changed in response to patients with different consultation participation styles. It was hoped that by documenting these behaviours we might be able to provide oncologists with a range of possible responses to different patient types, thereby permitting them to extend their existing behavioural repertoires in the consultation.

Materials and methods

This project was conducted with full human research ethics committee approval. A qualitative methodology was used in this study as this approach is most consistent with research questions that are aimed at addressing unexplored areas of inquiry. 16

Consultations between an actor and experienced medical oncologists were videotaped. The actor was trained to play the role of a patient who had recently undergone surgical treatment for early stage breast cancer, and was attending her first consultation with a medical oncologist. She adopted, in random sequence, two different consultation participation styles: that of an anxious, active patient, and that of a depressed, passive patient. Patient typologies were developed on the basis of a literature review and a consensus process with an expert panel of medical oncologists and psychologists involved in cancer care. The active patient was defined as one who was actively engaged during the consultation; this was indicated by her use of non‐verbal cues (e.g. hand gestures) and verbal cues (e.g. asked lots of questions, repeatedly checked her understanding with doctors). She seized control early during the consultation, usually from the outset. For example, she asked to audiotape the consultation, usually before the doctors had introduced themselves to the patient; she talked most of the time; she set the agenda early in the consultation for what she was and was not prepared to discuss, and continued to restate this agenda to doctors who were not prepared to acquiesce; she interrupted the doctor; and she wanted to make her own decision about the treatment. The active patient usually commenced the consultation by telling the doctor that she already knew which treatment she wanted to receive; although she was capable of changing her opinion, depending on the advice given by the doctor. This patient also controlled her emotional expression throughout the consultation, presenting as a rather ‘tight‐lipped’ person with crossed legs and arms; this reflected her anxious and controlled demeanour. She was, however, able to verbalize her distress and did raise emotional issues with the doctors.

The passive patient was defined as one who was not actively engaged in the consultation; this was indicated by her use of non‐verbal cues (e.g. restricted body movement and posture) and verbal cues (e.g. little spontaneous speech, provided simple yes/no answers, asked few or no questions). This patient also failed to engage in the consultation; for example, she did not state her agenda, did not interrupt the doctor, did not indicate her treatment preference, and mostly elected to have the recommended treatment or else she attempted to defer the decision to the oncologist. Finally, this patient tended not to control her emotions during the consultation; she presented as a subdued patient who was visibly anxious and weepy. She did not freely verbalize her emotional distress, however, to the doctors.

All medical oncologists in the Sydney region (n = 42) were invited to participate in the study. A referral letter was provided to all participating doctors the day prior to the videotaped consultations. This letter outlined the woman's medical history, the results of her pathology report (including axillary lymph node and hormone receptor status) and the outcome of her surgery. Oncologists were asked to discuss the following types of adjuvant chemotherapy with the patient: Adriamycin (12 weeks) or Cyclophosphamide Methotrexate Fluorouracil (CMF) (6 months). Consultations were conducted in an oncology clinic room at one of a number of teaching hospitals. Medical oncologists conducted the consultation as they would normally until the treatment options had been canvassed and discussed, and decision‐making negotiated (which took an average of 15 min). The consultation was then ‘cut’ until the closing segment when the actual decision (whether to delay, finalize or defer decision‐making) was negotiated (on average 5 min). Consultations were interrupted according to the above protocol, so as to reduce the duration of filming and the fatigue experienced by participants. At the end of the first role‐play, participants relaxed for 5 min, then began again with the patient adopting the second participation style (order was decided on a random basis). Thus, approximately 40 min of filmed interaction was obtained for each doctor. Doctors were asked at the end of the session how realistic they had found the patient roles. All doctors commented that they had encountered both patient types in real life. They also noted that the assertive patient was not an extreme example (they had encountered more ‘aggressive’ patients), and that they far preferred the active to the passive patient. They were generally concerned that the passive patient was not coping well and were anxious to help her. At the conclusion of the session, when the doctor had left the room, the actor was asked to briefly describe her response to the interactions with the doctor; the actor was not prompted to answer in any particular way.

Analysis

Videotaping of doctors continued until no new behaviours were observed on two consecutive videotapes, that is, until theoretical saturation was reached. This was achieved after 16 consultations. The videotapes were analysed qualitatively by two trained raters (RFB and PNB) to determine the impact of the different patient participation styles on doctors' behaviour. The consultations were analysed using grounded theory. 17 , 18 In doing so, we adhered to the process of defining mutually exclusive categories of behaviour, sorted into higher order themes, typically used in grounded theory to organize and make sense of narrative material. In conducting our coding, separate copies of the transcripts were given to both raters for analysis. The transcripts were stratified by patient type, and behaviours which appeared with one patient type but not the other, were noted. Each level of coding then generated a discussion between the two raters about how the categories, codes, and eventual themes emerging from the narrative material ought to be named or described. These discussions continued until a consensus was reached. Characteristic examples of each category were identified to illustrate its meaning.

While the analysis was intended to describe the range of behaviours doctors exhibited in responding to the patient types, it became clear that certain behaviours had greater integrity within the consultation. These behaviours resulting in a regression back to the ideal of shared decision‐making as described in the literature in both patients, and a calmer conclusion to the consultation. Furthermore, the actor provided some feedback concerning her preferred behaviours. While not a formal or in any sense complete evaluation of the strategies described, these observations are presented in the Results and further explored in the ‘Discussion’.

Results

The sample

The sample consisted of 16 medical oncologists who were employed in seven major teaching hospitals in the Sydney Metropolitan area. Twelve male and four female doctors participated in the study. Doctors were on average 46.7 years of age (SD = 7.0; range = 36–59 years), and had an average of 15.6 years (SD = 6.8; range = 5–27 years) experience as consultant oncologists.

General responses to the active style

Common doctor responses to salient patient cues used by the active patient are detailed in Table 1.

Table 1.

Common doctor responses to the active patient (n =  16 )

Patient cues Common responses by doctors Other responses by doctors
Asked to audiotape consultation Affirmed patient's request ( 16 )
Took control of consultation Took back control at certain times ( 13 ) Directly reprimanded patient ( 1 )
Warned patient not to rush decision ( 1 )
Permitted patient to maintain control ( 1 )
Repeatedly asked questions Responded positively ( 15 ) Gave full attention to patient ( 5 )
Validated patient's question asking ( 5 )
Answered before patient finished question ( 3 )
Used visual cues to hurry patient along ( 3 )
Periodically interrupted doctor Addressed questions/comments ( 12 ) Raised voice and talked over patient ( 2 )
Raised hand in ‘stop’ sign ( 1 )
Encouraged patient to interrupt at anytime ( 1 )

Most doctors responded positively to this patient's attempts to control the consultation (e.g. by agenda setting) and to her periodic interruptions. However, most doctors took back control of the consultation with the active patient at certain critical times, apparently so that important information would not bemissed. For example, doctors took back control in order to introduce themselves, state their agenda for the consultation, ask specific questions of the patient, review the pathology report or to outline the available treatment options. Sometimes this transition was smooth, particularly if the doctor settled into a question‐response format that was directed by the patient. However, at other times a ‘battle of wills’ ensued as doctors entered into a protracted battle for control with the patient. On one occasion, this culminated in both the patient and doctor repeatedly interrupting each other and raising their voices to control the consultation.

One positive strategy employed by doctors was to explicitly negotiate with the patient. For example, one doctor responded to the active patient's question‐asking by inquiring ‘Do you want to start or shall I’?, and another asked ‘How would you like to do it? Would you like to ask me your questions first, or would you like us to talk about what has happened so far…which would you prefer?’ Some doctors also endorsed the active patient's question‐asking (e.g. by indicating that hers were important, sensible and commonly asked questions).

Some doctors took more active control but offered a compromise; for example, one oncologist said ‘What I’ll do is go over what's been done…and then I'm happy to answer your questions', and another said that he needed to ask some questions about her past medical history but was ‘happy to wait until the end of the consultation to do this’. Others stated they would take control, but gave a rationale for this; for example, one doctor asked the patient to detail what she understood of her medical history, despite her stated desire to progress to treatment options, so as to ‘avoid repeating things or labouring the point unnecessarily’.

One doctor tried to slow down the active patient, by touching her on the knee to get her attention, making calming gestures and talking slowly to her.

General responses to the passive style

Common doctor responses to salient patient cues used by the passive patient are detailed in Table 2.

Table 2.

Common doctor responses to the passive patient (n =  16 )

Patient cues Common responses by doctors Other responses by doctors
Did not take control of consultation Took control/outlined agenda (16) Checked if happy being asked questions (1)
Asked closed questions (16) Checked if happy following doctor agenda (1)
Little spontaneous speech Checked patient's understanding (13) Did not check understanding (3)
Repeatedly checked understanding (7)
Did not ask questions Asked if patient had questions ( 14 ) Asked if patient had questions at end  of consult ( 4 )
Repeatedly asked if patient had  questions ( 7 ) Expressed concern at lack of questions ( 3 )

All doctors responded to the passive patient's silence by talking the vast majority of the time, after outlining their own agendas. They attempted to elicit a response by asking numerous closed‐ended questions. A few doctors directly addressed her lack of response; for example, one doctor asked how much she knew and wanted explained and whether ‘this is what [she] expected to hear?’, one checked how she was coping with the amount of information being presented to her, and another expressed his concern that the patient did not seem to be taking things in.

Most doctors appeared anxious that they were not getting any feedback from the patient and tried various strategies to reassure themselves that she had adequately understood the major issues. For example, some asked her to explain what she knew and then corrected her errors in understanding, some asked her if she understood what was being said, and some asked her if she wanted any particular issue explained in more detail.

Providing information and responding to emotional cues

Differences in the provision of information and responses to emotional cues to the active and passive patients are detailed in 3, 4.

Table 3.

Differences in information provision to the active andpassive patients (n =  16 ); number of consultations inwhich each behaviour occurred

Doctor behaviours Active patient Passive patient
Gave simple explanations/used little  medical jargon 1 8
Used pictures/simple analogies 1 5
Made treatment notes for patient 3 4
Educational materials, scientific papers  and website URLs 4 2
Stressed importance of repeating  information 1 4

Table 4.

Doctor responses to the active and passive patients' emotional cues (n =  16 ); number of consultations in which each behaviour occurred

Doctor behaviours Active patient Passive patient
Raised emotional issues with patient 2 13
Addressed potential fears 3 13
Reassured patient of probable good  outcome 4  7
Asked about social and family support 1  5

Doctors provided fewer details and less complex information to the passive patient, apparently in response to her clearly overwhelmed emotional state. In addition, doctors used more strategies to facilitate her understanding, such as diagrams.

Doctors raised emotional issues more often with the passive patient than they did with the active patient. They more often asked the passive patient how she ‘took the news of the cancer’, how she was feeling emotionally, and whether she had experienced any other major loss or fear. Doctors also highlighted emotional problems that had been experienced by other women with breast cancer, asked the passive patient more often about her family and social support and tended to speak more softly, slowly and less animatedly to the passive patient.

Some doctors directly challenged the passive patient about the way in which she was coping. For example, one doctor said ‘I sense you’re not coping as well as you possibly could', while another said ‘You can think positively … you can beat it…it is good to think that, and try and get on top of it, don’t you [think]?'

Doctors addressed the passive patient's fears about the disease and its treatment, and actively tried to reassure her about her prognosis more often than they did with the active patient. For example, one doctor said very early in the consultation ‘The first thing to say is your breast cancer is gone – you don’t have it any more', while another stressed that ‘the goal of treatment is cure’. Doctors also tried to reassure the passive patient about her own capacity to cope. For example, some doctors told the passive patient she would feel less anxious after starting the chemotherapy, that she would ‘sail through the treatment’, and that the medical staff would ensure her treatments went smoothly.

On the other hand, some doctors did not address the active patient's fears regarding her medical outcome, perhaps assuming her drive for information indicated no needs in this area. In one consultation, the active patient indicated that she was fearful of how she might cope emotionally and whether or not she was going to die. The doctor simply responded to her by saying ‘Well, you’re right, the risk probably is about 50:50' and then resumed his discussion of the treatment options.

Treatment decision‐making with the active and passive patients

Differences in oncologists' approach to treatment decision‐making and the provision of psychosocial services to the active and passive patients are detailed in Table 5.

Table 5.

Treatment decision‐making and the active and passive patients (n =  16 ); number of consultations in which each behaviour occurred

Doctor behaviours Active patient Passive patient
Gave a definite treatment  recommendation  9 12
Encouraged patient to make own  decision 15 10
Suggested that patient seek a  second opinion  4  1
Suggested delay in treatment decision  6  6
Offered services/referrals to patient 12  9
Offered after‐hours phone contact  number  6  1
Offered access to psychology/social  work services  1  4
Offered second family oriented  consultation  1  6
Offered access to breast cancer  support services  3  4

Doctors gave a definite treatment recommendation more often to the passive patient, than they did to the active patient. Most doctors seemed to consider patient preferences, for example, by asking her how she felt about particular treatment‐related side‐effects. Some doctors explicitly informed the patients that they were taking individual factors into account when making their recommendations. For example, one doctor indicated that his recommendation would be ‘personalized’ although her case was fairly routine, whereas the other emphasized that she was ‘not a statistic’, although he would often be referring to statistics.

Doctors more often encouraged the active patient to make her own decision about the treatment, than they did with the passive patient. In general, doctors nominated their primary role with the active patient as one of ‘information provider’, and they generally stressed that the treatment decision rested with her. A typical response of these doctors was: ‘Are there any other things you need me to do in order for you to make a decision?’ However, some doctors were apparently unsettled by the active patient's forthrightness in making her own decision. For example, one doctor asked the patient ‘exactly what are you trying to decide?’, and one maintained that the ‘decision should be made jointly’ although the patient had indicated that she wanted to make her own decision about the treatment. One doctor cautioned that the treatment options should be explained fully before a decision was made: ‘you may have read things now and feel you know it all, but there may be other things you find out later … and you will be upset if I don’t present all the options'. In addition, doctors generally suggested a second opinion only to the active patient, and not to the passive patient.

Doctors often tried to push the passive patient to make her own decision about the treatment. Typical doctor responses were ‘Really, the decision is up to you, if you’d like to make it … I wouldn't feel that one treatment was better than the other … what do you think?', ‘my job is to support you through the treatment’, ‘my job is to give you advice about the choices, guide your decisions, and support you’ or that ‘I don’t want you to feel pushed into something … I want you to be able to make an informed choice'.

Some doctors suggested that the patient should delay her treatment decision, at least until she had spoken to her family, chemotherapy nurse or other source. This appeared to be a response to the passive patient's attempts to defer responsibility for the treatment decision, and the active patient's urging to ‘get the treatment over with’.

Actor/patient preferences for individual doctor characteristics

Those doctors who attempted to put the patient at ease by smiling, greeting and regarding the patient warmly, and attempting to inject some humour into the consultation, were those most positively endorsed by the actor/patient. These doctors also displayed appropriate verbal and non‐verbal cues to indicate their willingness to listen (e.g. relaxed posture, good eye contact) and responded appropriately to her salient patient cues (e.g. empathic tone and language, moving closer/touching the distressed patient). Conversely, those doctors who were the least endorsed by the patient/actor were those who did not smile, employed a business‐like approach, and appeared to be emotionally detached. These doctors also tended not to elicit information of a personal nature (e.g. occupation, number of children) from the patient, or they were inflexible in the way they allowed the consultation to be conducted.

Interestingly, those doctors who were most positively endorsed by the patient/actor were able to influence the actor into becoming a more ‘interactive’ and less extreme patient. That is, in their presence, the active patient became more co‐operative, and the passive patient became more active.

Discussion

Strengths and limitations

This study explored oncologist responses to active and passive patients when a treatment decision had to be made. The study was a qualitative exploration of doctor responses to two patient participation styles (active and passive). We used a trained actor to ensure that all doctors responded to the same stimulus. This is a strength of the study, as we know that variations in doctor response were the result of the variable being manipulated (patient response style) rather than differences in the patient's personal presentation, gender, cancer type, or issues raised. Furthermore, we were able to elicit feedback from the actor in a way that could not be ethically achieved with real patients. However, this strategy also limits the ecological validity of the study, in that doctors may behave differently in their own consultation rooms with real patients. The fact that all doctors found the patient roles convincing suggests that we did garner at least some of the range of responses real patients might receive.

While some of the responses appeared in the context of the consultation to be more effective than others, and while the actor gave informal feedback regarding her preferred interactions, we did not set out to formally evaluate the impact of different responses on patient outcomes. Comments by the actor are limited to her personal views, and may not reflect the opinion of other patients. Further research is required to explore ‘ideal communication’. However, it is hoped that this fine‐grained analysis of doctor responses will provide the reader with some new ideas about how to optimize their communication with both passive and active patients.

On the whole, doctors found a way to move forward with both patient types. Some strategies used by oncologists were particularly effective in dealing with the active patient, in that they appeared to facilitate a shared decision‐making approach. These strategies included giving the patient their full attention when she was asking questions, positively responding to her periodic interruptions and questions, settling into a question‐response format that was directed by the patient, and periodically taking back control of the consultation to review important information. In particular, one of the most effective strategies used by doctors to deal with the controlling behaviour of the active patient was to first acknowledge her agenda, then communicate their own agenda, and then offer the patient a choice of how she would like the consultation to be conducted. Finally, those doctors who suggested to the active patient that she should delay her treatment decision until after she had talked to the chemotherapy nurse, other oncologists and/or family members, increased the likelihood that she was making an informed decision.

Some strategies were also particularly effective in dealing with the passive patient. These strategies included checking and rechecking the patient's understanding, responding to her salient emotional cues, normalizing distress, discussing coping strategies and suggesting that she delay the treatment decision until after a second consultation with the oncologist, or after she had talked to the chemotherapy nurse and/or family members.

Doctors also used strategies that were not so effective in dealing with the active and passive patients. For example, some doctors directly challenged the active patient about her participation style or they were inflexible in the way they allowed the consultation to proceed, some challenged her desire to make her own decision about the treatment, and some even entered into a protracted battle for control of the consultation. On the other hand, some doctors failed to elicit a treatment preference from the passive patient. Interestingly, few doctors checked either patients' preferences for information provision, or their expectations and preferences for their role in treatment decision‐making, apparently relying on their own assessments of the patient, suggesting that some standard components of shared decision‐making 14 , 15 are not commonly used in practice.

Those doctors who smiled the most, greeted and regarded the patient warmly, and attempted to inject some humour into the consultation were those who were the most positively endorsed by the patient/actor. These doctors also appeared to be able to facilitate a more interactive and shared approach to decision‐making. This result is interesting given our previous finding 19 that cancer patients describe their personal relationship with the oncologist and their evaluation of his or her openness and honesty, as major factors influencing their treatment decision‐making. Together, these findings suggest that patients need to have established a comfortable, supportive relationship with their doctor, before feeling able to play an active role in an interaction which involves interacting with an expert, often perceived to be of higher social class, concerning issues of vital importance, and which are highly emotionally laden. Simply asking what role the patient wants to play in decision‐making and offering a choice, may not be enough to truly facilitate shared decision‐making with many patients.

In summary, this study has identified a range of strategies in dealing with two different patient types. The results suggest that adaptation to the patient's participation style requires sensitivity to cues and flexibility. However, core elements identified by this and other studies that assist in collaborative decision‐making and the forming of an open and trusting relationship might usefully be integrated into every consultation.

Acknowledgements

The authors would like to thank the following oncologists for kindly participating in the study: Dr Keiren Phadke, Prof. Fred Kirsten, Dr John Kearsley, Dr Stephen Ackland, Dr David Goldstein, Dr Nicholas Wilcken, Dr Ann Sullivan, Dr Michael Boyer, Dr Martin Stockler, Dr Peter Ellis, Dr Amanda Goldrick, Dr Helen Wheeler, Dr David Bell, and Prof. John Levi. This work was supported by the National Health and Medical Research Council of Australia (Grant no. 970735).

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