Editorials Articles

Humble beginnings to life changing discoveries

Welcome to Volume 3, Issue 1 of the Australian Medical Student Journal. As always, we hope this issue offers excellent food for thought for budding doctors and researchers.

From our deputy editor, Hasib Ahmadzai, comes an editorial reflecting on the role of medical students in medical discoveries in the past. It goes to show that when medical students get to work, it is amazing just what we can achieve!

Australian of the Year and plastic surgeon Prof Fiona Woods entertains us with stories of how her early experiences stretched her mind and informed her later discoveries. Our other guest author, Sir Gustav Nossal, uses his decades of research experience in immunology to provide an insightful discussion on the serious inequalities present in global health.

The award for best article for Volume 3, Issue 1 of the AMSJ goes to Matthew Bray and Daniel Keating for their original research on ‘Immunisation and informed decision making amongst Islamic primary school parents and staff’. Their research was considered by editorial staff to be robust in methods and offering a unique perspective on an issue that is not often considered by practitioners in Australia.

As a young journal, we host many changes each time we go through the publication process as we strive to continually innovate and bring readers the highest quality of student research publication.

The editorial department has undertaken many of these changes. One of our aims has been to make the AMSJ a truly Australia-wide medical journal. This issue is the first for which we have recruited editorial and production staff from almost every state. Our team has welcomed seven new editors and now represents ten different Australian universities. With both rural and urban students on board, we believe that the AMSJ is well equipped to encourage research across a wide range of medical practice settings.

This is also the first time that the publication process has primarily taken place through email and teleconference, rather than face-to-face meetings. We have particularly benefited through the adaptation of cloud technology. With this change, remote collaboration has been made easier and more efficient.

While we have engaged Australia on an organisational level, this issue sees further efforts to bring equal readership and access to the journal for all Australian students, regardless of location. This has culminated in distribution to not just every medical school in Australia, but also their 50 rural clinical schools and campuses.

Furthermore, the AMSJ website has seen many advances to keep pace with current technology, including a touch-friendly mobile website (which can be found on your smartphone at

Other upcoming events include the next round of recruitment for the AMSJ team in August this year. We would strongly encourage enthusiastic and dedicated medical students to apply for one of the many roles available. This is a unique opportunity to become part of a growing national organisation which encourages development of critical thinking, teamwork and research publication skills.

We would like to extend our thanks to all of the voluntary AMSJ staff and external peer reviewers for their invaluable efforts in the production of this issue. To our readers: thank you for your continued support and we hope you will share our passion for medical student research.

Articles Editorials

Ranking the league tables

University league tables are becoming something of an obsession. Their appeal is testament to the ‘at a glance’ approach used to convey a university’s standing, either nationally or internationally. League tables attract public attention and shape the behaviour of universities and policy makers. Their demand is a product of the increasing globalisation of higher education, tighter allocation of funding, and ultimately the recruitment of foreign students. Medical schools are not immune to this phenomenon, and are banished to a rung on a ladder year after year according to a formula that aggregates subjectively chosen indicators. While governments and other stakeholders are placing growing importance on the role of league tables, it is necessary to scrutinise the flaws in their methodology and reliability in measuring the quality of medical schools.

Academic league tables, the brainchild of Bob Morse, were developed for the US News and World Report 30 years ago. [1] They were pioneered to meet a perceived market need for more transparent, comparative data about educational institutions. [1-3] Despite being vilified by critics, several similar ranking systems emerged in other countries in response to the introduction of, or rise in, tertiary education tuition fees. [1-3] League tables have since garnered mass appeal and now feature as a staple component of the education media cycle. They often take on the form of ‘consumer guides’ produced by commercial publishing firms who seek a return for their product. [1]

Although in existence for less than a decade, the Times Higher Education (THE) World University Rankings, along with the Quacquarelli (QS) World University Rankings and Shanghai Jiao Tong University Academic Ranking of World Universities are considered the behemoths of international university rankings. They provide a snapshot of the top universities overall and by discipline. From 2004 to 2009 THE, a British publication, in association with QS, published the annual THE–QS World University Rankings, however, the two companies then parted ways due to differences over methodology. The following year, QS assumed sole publication of rankings produced with the original methodology, while THE developed a novel rankings approach in partnership with Thomson Reuters. Many countries also generate national rankings by pitting their universities against each other – Australia’s answer being the Good Universities Guide.

League tables employ various methodologies to rank universities. Most involve a three stage process: first, data is collected on indicators; second, the data for each indicator is scored; and third, the scores from each indicator are weighted and aggregated. [3] The THE rankings use thirteen performance indicators, grouped into five areas including teaching, research, citations, industry income and international outlook. [4] Teaching has a 30% weighting and constitutes a reputational survey (15%), PhD awards per academic (6%), undergraduates admitted per academic (4.5%), income per academic (2.25%) and PhD/Bachelor awards (2.25%). [4,5] QS also uses a similar construct to render their final rankings. In contrast, the Shanghai rankings are established solely on research credentials such as the number of Nobel- and Fields-winning alumni/faculty and highly cited researchers, and the number of non-review articles published in Nature and Science. [6]

The influence of ranking tables has grown to such an extent that various vested interests indulge in rankings for different reasons. [1-3,7-9] A 2006 international survey revealed that 63% of higher education leaders made strategic, organisational, managerial or academic decisions based on rankings. [7] This is not always for the benefit of students or staff, and sometimes simply reflects the desire of a senior team to appear to have had an easily-identifiable impact. It is claimed that rankings have also influenced national governments, particularly in the allocation of funding, quality assessment and efforts to create ‘world class’ universities. [8] Furthermore, there is limited evidence that employers use ranking lists as part of the selection of graduate recruits. [8]

Academic league tables are no strangers to criticism, reflecting methodological, pragmatic, moral and philosophical concerns. Critics argue that ranking lists have applied the metaphor of league tables from the world of sport; a simplistic and incapable tool for evaluating the complex systems of higher education. [3] Rankings are guided by ‘what sells in the market’ rather than the rigorous quality assurance practices of academic bodies.

The world’s main ranking systems bear little resemblance to each other, owing to the fact that they use different indicators and weightings to arrive at a measure of quality. [1-3,8,9,11] According to a study by Ioannidis et al., [10] the concordance between the 2006 rankings by Shanghai and the Times is modest at best, with only 133 universities holding positions in both of the top 200 lists. The publishers of these tables impose a specific definition of quality onto the institutions being ranked, by arbitrarily establishing a set of indicators and assigning each a weight with little theoretical basis. [1-3,8] Readers are left oblivious to the fact that many other legitimate indicators could have been adopted. To the reader, the author’s judgement is, in effect, final. Many academics are of the view that rankings do not take into account the important qualities of an educational institution that cannot be measured by weightings and numbers. [8]

Statistical discrepancies also compound the tenuous nature of league tables. Often institutions are ranked even when differences in the data are not statistically significant. [1-3,8] There have been many instances where data to be used in compiling ranking scores are missing or unavailable, especially in international comparisons. [1-3,8] Moreover, data availability is a source of bias, whereby publishers opt for convenient and readily-available date, at the expense of accuracy and relevancy. [1-3,8]

Another cause for concern is that rankings place a significant emphasis on research while minimising the role of education in universities. [5] Most educators would recognise that the indicators for quality teaching and learning are limited. [1-3,8] Various proxies for teaching ‘quality’ are used, including average student-staff ratios. [1-3,8,11] The lack of robust data relating to teaching quality is attributed to its difficult, expensive and time-consuming nature. [2] When considering that teaching quality is one of the key dimensions of medical education, its neglected importance severely compromises the meaning of any data produced by these tables.

The main mechanism for quality assurance and evaluation amongst medical schools at present is regular accreditation by national or regional accreditation bodies. [5] The Australian Medical Council (AMC) is responsible for setting out the principles and standards of Australian medical education, including assessment. The ‘one-size-fits-all’ approach of ranking tables is a futile means to effectively measure the quality of medical schools. Medical education is characterised by a range of unique indicators, for example, clinical teaching hours and global/rural health exposure. As a direct consequence of accreditation bodies, most medical schools deliver a consistent level of education and yield competent interns to practice in the Australian healthcare system. By contrast, league tables are over-simplified assessment tools for evaluating the quality of medical education, and even have the potential to harm the standards of education. [10]

Although league tables are not exalted and revered to the same degree as in the US or Europe, Australia is inadvertently heeding this imperious trend. League tables are nothing more than ‘popularity polls’, and should not become an instrument for measuring the quality of universities and medical education.


[1] Usher A, Savino M. A world of difference: a global survey of university league tables. Toronto (ON): Education Policy Institute; 2006 Jan. 63 p.

[2] Stella A, Woodhouse D. Ranking of higher education institutions. Melbourne: Australian Universities Quality Agency; 2006 Aug. 30 p.

[3] Marginson S. Global university rankings: where to from here. Asia Pacific Association for International Education. 2007 Mar 7-9; Singapore. Melbourne: Centre for the Study of Higher Education; 2007 Mar.

[4] Baty P. Rankings methodology. Times Higher Education; 2011 Oct 6. [updated 2012; cited 2012 Apr 7]. Available from:

[5] Harden RM, Wilkinson D. Excellence in teaching and learning in medical education. Med Teach. 2011;33:95-6.

[6] Liu NC, Cheng Y. The academic rankings of world universities. Higher Education in Europe. 2005 Jul;30(2);127-36.

[7] Hazelkorn E. Handle with care [Internet]. Time Higher Education; 2010 Jul 8. [updated 2010 Jul 8; cited 2012 Apr 7]. Available from: asp?storycode=412342.

[8] Lee H. Rankings of higher education institutions: a critical review. Qual High Educ. 2008 Nov;14(3):187-207.

[9] Saisana M, D’Hombres B. Higher education rankings: robustness issues and critical assessment. Luxembourg: Office for Official Publications of the European Communities; 2008. 106 p.

[10] Ioannidis JPA, Patsopoulos NA, Kavvoura FK, Tatsioni A, Evangelou E, Kouri I, Contopoulos-Ioannidis DG, Liberopoulos G. International ranking systems for universities and institutions: a critical appraisal. BMC Med. 2007 Oct 25; 5(30).

[11] McGaphie WC, Thompson, JA. America’s best medical schools: a critique of the U.S. news and world report rankings. Acad Med. 2001 Oct; 76(10):985-92

Articles Editorials

The clinician-scientist: Uniquely poised to integrate science and medicine


Growing in the world of academic medicine is a new generation of doctors known as “clinician-scientists”. Trained in both science and medicine, with post-graduate research qualifications in addition to their medical degree, they serve as an essential bridge between the laboratory and clinic.

The development of sophisticated experimental approaches has created opportunities to investigate clinical questions from a basic science perspective, often at a cellular and molecular level previously impossible. With new and detailed understanding of disease mechanisms, we are rapidly accelerating the discovery of new preventative measures, diagnostic tools, and importantly, novel therapeutic approaches. In these emerging avenues there is not just a need for collaboration between scientists and clinicians, but a need for individuals who are fluent in both science and medicine – hence, the advent of clinician-scientists. The terms “translational research” or “translational medicine” are often associated with clinician-scientists, alluding to the notion that these people facilitate the two-way process of translating scientific findings into clinical applications (bench-to-bedside), and provide clinical data and specimens back to the laboratory to investigate underlying disease processes (bedside-to-bench).

From a student’s perspective however, these concepts can be confusing and finding their way through the breadth and categories of research conducted in academic institutions and hospitals may prove daunting. A discussion of the clinician-scientist niche and some of the challenges and opportunities faced may prove helpful.

Defining the clinician-scientist

Most clinicians at an academic hospital are engaged in research to some extent, but this tends to be mainly clinically-oriented, with patient care, treatment outcomes, and population health being broad areas commonly involved. Their day-to-day job is mostly defined by their clinical duties, often with some teaching responsibilities involved. Clinician-scientists, by contrast, dedicate a significant proportion of their time to research, typically spending ≥50% protected time in order to be remain academically competitive. [1] Whilst still loosely defined, in a purist sense this is a clinician who is involved in research at an organ, tissue, cellular, or molecular level, as opposed to focussing solely on whole patients as a clinical subject. Such research may not always have clinical findings that are directly relevant to everyday medical practice but the difference from a pure basic scientist is that the science has been approached with clinical relevance in mind. Interestingly, on the other hand, science itself has become inter-disciplinary and is recognising the importance of clinical relevance and translation with new ventures such as the Stanford University PhD in Stem Cell Biology where graduate science students interested in involvement with translational research in regenerative medicine undertake rotations shadowing clinicians in order to develop a clinical perspective to their research. [2] These developments indicate that not only are the frontiers between science and medicine becoming blurred, but that translational research is the exciting intersection where clinician-scientists, as well as scientists well-attuned to clinical practice, are uniquely poised to thrive.

The clinician-scientist niche

Clinician-scientists possess a distinctive set of skills, being trained as a clinician to apply scientific knowledge to patient care, and trained as a scientist with an enquiring mind designed to test hypotheses. Understanding the clinical relevance of observations in science and the ability to translate this back into clinical practice is truly the domain of the clinician-scientist, and uniquely so.

The pursuit of additional post-graduate research qualification such as a Masters or PhD has traditionally been the main pathway to becoming a clinician-scientist in Australia, unlike in the United States where combined MD-PhD programs have been well established in the past. However, the recent development of similar combined MBBS-PhD and MD-PhD programs in Australia is likely be instrumental in building a body of clinician-scientists that have been moulded specifically for this task. [3] Skills developed in scientific training essential for success in research include literature appraisal, manuscript and grant writing, and mastery of laboratory techniques, all of which are life-long skills honed over time, and which are rarely acquired in medical school.

It goes without saying that clinician-scientists are expected to be experts in both medicine and science. Anything subpar of clinical competence would pose a threat to patient safety and cannot be compromised. On the other hand without a solid commitment in research with the appropriate output in terms of publications, conference attendance, and grant proposals, a career in research will not take off since a track record is something that needs to be built on constantly. Given that clinical training itself takes a good number of years before being able to practice as an independent clinician it is little wonder that many are unwilling to tackle both clinical and scientific careers at once. Again, this lends further credence to the MD-PhD path where scientific training would have already been completed by the end of the program, although this itself has its drawbacks, since the science gained can become neglected in the last clinical years and will need to be polished again upon completion. [4]

But where lie challenges also lie opportunities: for the determined few, funding statistics indicate that the rigorous training is entirely worthwhile. Clinician-scientists have been found to consistently perform better in national funding programs such as the National Institutes of Health Research Project Grants (United States) than their pure clinician (MD only) and basic science (PhD only) counterparts. [5] Although the pool of clinician-scientists in Australia is significantly smaller than that of the United States and data on funding trends are less widely discussed in literature, it is generally acknowledged that clinician-scientists also do well in obtaining NHMRC funding. This may be due partly to the fact that clinician-scientists are afforded more flexibility in labelling their projects as “basic science” or “clinical”, and therefore have access to funds for both basic science and clinical projects, whereas pure clinicians and scientists are generally limited to their own funding areas.

When describing the clinician-scientist niche, an aspect of research “translation” that is often neglected is the importance of the delivery of research-based medicine into actual practice. The classic bench-to-bedside process refers to the invention of a new drug, device, or diagnostic tool where the hope is that it will undergo clinical evaluation in a controlled setting with a specific patient cohort. But bringing a discovery into the market is simply the beginning, and to bring this to the general public a much more concerted effort is required involving collaboration between public health experts, policy makers, and clinicians amongst others. So drawn-out and complex is the process that it is well acknowledged that this area of “translational” research often fails, with many potentially important discoveries unable to make changes to everyday medical practice.

[6] However, clinician-scientists are well suited to play an active role in negotiating the many hurdles in this endeavour by facilitating communication between the various experts involved, whilst providing a first-hand inventor as well as treating clinician’s perspective that is not only unique but critical in ensuring that an invention is appropriately implemented and evaluated. In the Australian context, the National Health and Medical Research Council (NHMRC) has recognised this gap in research translation and the Centres for Research Excellence and Translating Research Into Practice (TRIP) Fellowships are specific measures aimed to address this issue. [7]

Wearing two hats: double the challenges?

A commonly quoted recommended research:non-research ratio for workload is 75:25, with the majority of time devoted to research in order to succeed as a clinician-scientist. [8] In reality this is more likely to be exactly opposite the case, where a 75:25 ratio in favour of clinical work becomes the norm instead. [9] This may be particularly so in the early years after graduation when specialist training is being undertaken, despite the fact that this is also the time when a solid research foundation needs to be built in order to establish a clinician-scientist’s academic presence. As pressing as clinical demands may be, it is widely recognised that a research career cannot flourish without negotiating some protected time from clinical duties with the hospital department.

The biggest challenge for clinician-scientists is therefore time management. In addition to patient care, clinical training, and teaching responsibilities, clinician-scientists are expected to undertake labwork, keep abreast of advances in both scientific and medical literature, and engage in professional development and conferences on both fronts. They must maintain manuscript preparation and grant proposals, complete administrative duties, and often lead research teams. To realistically keep up with these demands of juggling a dual career, the ability to delegate and seek cooperation from scientist and clinician colleagues is critical. The lack of a supportive environment and a suitable mentor who can share their experiences and show the way can present an impossible struggle to the time-constrained clinician-scientist.

On the clinical front, to manage their workload clinician-scientists may tightly focus their interests to subspecialised areas to maintain an adequate caseload and expertise without stretching oneself too thin. This depends however on working in an environment where the volume and diversity of patients permits such subspecialisation, with appropriate facilitation by supervisors such as Department Heads. Unfortunately these conditions tend to be found only in major tertiary hospitals, relegating clinician-scientists to these settings.

Additionally, a research career is often less financially rewarding than clinical work particularly when private practice may need to be sacrificed in order to undertake lab work. This can pose a significant barrier particularly because the number of years required to gain appropriate training results in clinician-scientists being likely to be older than their scientist and clinician counterparts and may therefore have family commitments, and have often also accumulated student debts that need to be repaid. [10] Some solutions to this may be the Practitioner and Career Development Fellowships offered by the NHMRC aimed at clinicians involved in research, [11] as well as hospital and philanthropic organisation funding specifically for buying time out from clinical practice for research.


Opportunities for the clinician-scientist




For any researcher, securing funding is a lifeline in continuing their work and burnishing a track record, and it is here where clinician-scientists can be creative in sourcing their benefactors. Philanthropic organisations often affiliated with a disease or clinical cause, specialist training colleges like the Royal Australasian College of Surgeons, hospital based foundations, pharmaceutical companies, and fundraising from patient advocates are all important and significant funding avenues that clinician-scientsts may find more accessible than pure scientists. [12] These grants often allow pilot projects to be undertaken in order to generate sufficient amount of preliminary data to become competitive for major research funding such as from the NHMRC. Additionally, a number of these organisations offer clinician-scientist fellowships similar to the NHMRC.

Apart from funding success, it has also been found that many clinician-scientists opt to apply for and are successful in obtaining university academic positions. [12,13] Such engagement in academia provides synergy for research efforts by opening up institutional resources often more diverse than hospital settings, prospects for networking with likeminded professionals and mentors.

Additionally, the scope translational research itself is widening. An increasing number of academic hospitals are dedicating departments to translational research, with clinician-scientists often taking the lead. The need to prioritise translational research has been further underlined by the Chief-Scientist of Australia’s recent speech calling for increase in research funding for this area. [14] Whilst these are positive developments, further input from clinician-scientists themselves is required to shape policy changes and design steps to increase their numbers.


Moving forward




An apt saying may be, “Clinicians know all of the problems, but none of the solutions; scientists know all of the solutions, but none of the problems”. [15] This is where clinicianscientists represent a unique breed suited to fulfil this vacant niche, and are absolutely necessary in forging the next success stories of medicine. Despite the complexities of a dual career, the rewards and satisfaction in pursuing this path are evident and meaningful, and can lead to tangible health outcomes in patients. Although it is important to maintain a realistic notion that being a clinician-scientist is by no means an easy feat, it is equally important to take hope that the best of both worlds can be experienced. These perspectives are increasingly acknowledged in the form of progresses being made in the right direction to encourage clinician-scientists. In light of this, perhaps it is well worth noting that there may never be a better time than now to venture into, and indeed take charge in riding this next wave of medical evolution.


[1] Archer SL. The making of a physician-scientist–the process has a pattern: lessons from the lives of Nobel laureates in medicine and physiology. Eur Heart J. 2007 Feb;28(4):510-2

[2] Stanford University School of Medicine, Institute for Stem Cell Biology and Regenerative Medicine. PhD Program: Curriculum Overview. [updated February 17th 2009; cited March 8th 2012]; Available from:

[3] Power BD, White AJ, Sefton AJ. Research within a medical degree: the combined MB BS-PhD program at the University of Sydney. Med J Aust. 2003 Dec 1-15;179(11-12):614-6

[4] Marban E, Braunwald E. Training the clinician investigator. Circ Res. 2008 Oct 10;103(8):771-2

[5] Dickler HB, Fang D, Heinig SJ, Johnson E, Korn D. New physician-investigators receiving National Institutes of Health research project grants: a historical perspective on the “endangered species”. JAMA. 2007 Jun 13;297(22):2496-501

[6] Woolf SH. The meaning of translational research and why it matters. JAMA. 2008 Jan 9;299(2):211-3

[7] McCallum J, Forster R. From the NHMRC: Research translation network targets the evidence-practice lag. Med J Aust. 2011;195(5):252

[8] Tai IT. Developing a clinician-scientist career. Clin Invest Med. 2008;31(5):E300-1

[9] Bosse D, Milger K, Morty RE. Clinician-scientist trainee: a German perspective. Clin Invest Med. 2011;34(6):E324

[10] Lander B, Hanley GE, Atkinson-Grosjean J. Clinician-scientists in Canada: barriers to career entry and progress. PLoS One. 2010;5(10)

[11] National Health and Medical Research Council. Fellowship Awards. [Internet] [updated December 21st 2011; cited March 1st 2012]; Available from:

[12] Hayward CP, Danoff D, Kennedy M, Lee AC, Brzezina S, Bond U. Clinician investigator training in Canada: a review. Clin Invest Med. 2011;34(4):E192

[13] Toouli J. Training surgeon scientists. ANZ J Surg. 2003 Aug;73(8):630-2

[14] Australian Government – Chief Scientist of Australia 2012. Can Australia afford to fund translational research? [updated April 3rd 2012]; Available from:

[15] Hait WN. Translating research into clinical practice: deliberations from the American Association for Cancer Research. Clin Cancer Res. 2005 Jun 15;11(12):4275-7

Articles Letters

Metformin and PCOS: Potential benefit to reduce miscarriage risk

I am writing in response to the review article by Wong (AMSJ Volume 2, Issue 2). [1] Polycystic ovary syndrome (PCOS) is associated with an increased risk of miscarriage, occurring in 30% of pregnancies. [2] Although the mechanism is unclear, several interrelated factors appear to increase the risk of spontaneous miscarriages, including higher luteinising hormone levels, obesity, hyperandrogenisation, insulin resistance and infertility treatments. [3]

The advantage of clomiphene citrate over metformin for induction of ovulation has been well published. However, successful achievement of pregnancy that results in miscarriage is perhaps more devastating to a patient than anovulation. The role of metformin is not restricted to its effects on infertility and ovulation alone and the potential for treatment of PCOS-related miscarriage should be acknowledged.

As medical students, we are taught to cherish randomised controlled trials and meta-analyses for their ability to eliminate potential retrospective and investigator bias. Meta-analyses [3,4] have examined the effect of metformin on miscarriage rates in PCOS patients, one as a primary outcome. [3] Both failed to demonstrate a statistically significant benefit of metformin administration on miscarriage rates. The statistical heterogeneity among the trials and authors’ recommendations, that further well-designed randomised trials were required, were of concern.

The seventeen trials included in the Palomba meta-analysis [3] were scrutinised. None of the trials examined miscarriage rates as a primary outcome. Nor were they sufficiently powered to detect differences in miscarriage incidence. Metformin administration in all trials was either ceased at human chorionic gonadotropin injection or diagnosis of pregnancy. Thus meta-analyses published to date can only indicate that there is unlikely to be a reduction of miscarriage rates in PCOS patients, when metformin is administered prior to conception and ceased in early pregnancy.

This is essentially consistent with preliminary evidence which suggests, continued use for the full first trimester or throughout pregnancy [5] may reduce miscarriage risk compared with earlier cessation. To our knowledge, only non-randomised studies have evaluated the effect of metformin use during pregnancy on outcomes in PCOS patients.

A pilot study suggested continuing metformin throughout pregnancy reduced first-trimester spontaneous miscarriage without teratogenicity. [6] These findings have since been repeated in other studies, with significant reductions in first-trimester spontaneous miscarriage rates. [7]

Although these results are promising, these studies were non-randomised, often retrospective and used historical miscarriage rates, contributing to potential bias. Further large, well designed randomised controlled trials examining miscarriage rate as a primary outcome in women who continue to take metformin in the first trimester are indicated.

Recurrent miscarriage with three or more consecutive early pregnancy losses affects about one percent of the population, but the prevalence of PCOS is 40% in this population; almost eight-fold higher than in the general population. [4] However, PCOS was only given a brief mention in the updated European Society of Human Reproduction and Embryology protocol for investigation and management of recurrent miscarriage and there was no mention of metformin as a possible treatment. [8]

Since this updated protocol, a case study of a PCOS patient with recurrent miscarriage demonstrated live birth after physiologic pregnancy with metformin administration before and throughout pregnancy. [9] This indicates a possible role for metformin in the setting of PCOS patients with recurrent miscarriage and supports a need for further investigation.

As for the safety of metformin administration during pregnancy, the Australian risk categorisation places metformin as a category C medication, indicating no evidence for any teratogenesis or adverse foetal effects, but lacks evidence to prove this definitively. Australian and long-term overseas research of metformin use in pregnant patients with diabetes mellitus or gestational diabetes mellitus demonstrates no evidence of teratogenesis. [10]

Of the studies with metformin administration during pregnancy in PCOS patients, there have been no reports of teratogenic effect. [6,7] Meta-analysis on limited data suggested no evidence of increased risk of major malformations when metformin is administered during the first trimester. [11]

In conclusion, metformin could still be an effective treatment of PCOS in the setting of miscarriage and recurrent miscarriage. Further large, well designed randomised controlled trials examining miscarriage rates in PCOS patients as a primary outcome are indicated. Metformin should be administered throughout the first trimester in these trials, consistent with promising preliminary evidence. Patients receiving metformin during pregnancy should be counselled of the risks, but can largely be reassured from the current safety evidence.


[1] Wong S. Management of infertility in the setting of polycystic ovary syndrome. Australian Medical Student Journal. 2011;2(2):45-8.

[2] Sagle M, Bishop K, Ridley N, Alexander FM, Michel M, Bonney RC, et al. Recurrent early miscarriage and polycystic ovaries. BMJ. 1988;297(6655):1027-8.

[3] Palomba S, Falbo A, Orio F Jr, Zullo F. Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2009;92(5):1646-58.

[4] Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Freitas V. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2009;(2):CD006105.

[5] Kattab S, Mohsen IA, Foutouh IA, Ramadan A, Moaz M, Al-Inany H. Metformin reduces abortion in pregnant women with polycystic ovary syndrome. Gynecol Endocrinol. 2006;22(12):680-4.

[6] Glueck CJ, Phillips H, Cameron D, Sieve-Smith L, Wang P. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril. 2001;75(1):46-52.

[7] Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod. 2002;17(11):2858-64.

[8] Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod. 2006;21(9):2216-22.

[9] Palomba S, Falbo A, Orio F Jr, Russo T, Tolino A, Zullo F. Metformin hydrochloride and recurrent miscarriage in a woman with polycystic ovary syndrome. Fertil Steril. 2006;85(5):1511.e3-5.

[10] Simmons D, Walters BNJ, Rowan JA, McIntyre HD. Metformin therapy and diabetes in pregnancy. Med J Aust. 2004;180(9):462-4.

[11] Gilbert C, Valois M, Koren G. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril. 2006;86(3):658-63.

Letters Articles

The cardiac surgeon, a dying breed?

The innovation of the cardiopulmonary bypass machine in 1951 had now allowed surgeons the ability to operate on the heart without any time constraints. It was not soon after that Russian Cardiac Surgeon, Dr. Vasilii Kolesov, had performed the first successful coronary artery bypass surgery. His success and the innovation of the heart valve prostheses had led to the rapid development of one the most glamorous specialities of medicine. Despite this dramatic rise of cardiac surgery there has only been modest technological advances within the field. Although noticeable improvements from the standard operation including arterial grafting, off-pump surgery, small incision surgery and endoscopic conduit harvesting have been made, the reluctance to tamper with original success has meant that only a niche group of surgeons have adopted such modifications. Outside the surgical realm, advances in the anatomic treatment of cardiovascular disease has been dramatic and paramount. Percutaneous transluminal coronary angioplasty (PTCA) has since progressed from primitive ineffective use of balloon angioplasty. New drug eluting stents and strong platelet inhibitors are available for the treatment of cardiovascular disease.

Coronary vascular disease is not the only cardiac entity that is amenable to catheter-based intervention. Indeed the treatment of valvular heart disease has now been attempted percutaneously with successful percutaneous aortic valve implants in patients with significant co-morbidities, unsuitable for surgical intervention, and balloon valvotomy in mitral valve stenosis. [1] Research however is evident that such percutaneous interventions (PCI) are by far inferior to the corresponding surgical approaches. Currently, percutaneous valvular interventions utilise first generation devices and one can be certain that newer devices that are more deliverable, user friendly, efficacious and safer will be available in the near future. Not too dissimilar to exponential growth of PTCA, the impact of percutaneous valvular interventions will soon be apparent. This is undeniably having numerous implications on the future of cardiac surgery. With an aging population and a preference for minimally invasive therapeutic intervention what does the future hold for cardiac surgery? In a study published by the Australian Institute of Health and Welfare, the number of PTCA operations has dramatically increased between 2000–2001 and 2007–2008 with the number of PCIs performed increasing by 57%. [2] Subsequently there has been a 19% reduction in the number of coronary artery bypass grafts performed between 2000–2001 and 2007–2008, from 16,696 to 13,612. [2]

Extrapolation of the above data shows clearly that there will be a reduction in the number of operations performed through median sternotomy. However this route is not obsolete, nor will it be so in the near future. Despite the advances in PTCA, the surgical approach is still required for those with multivessel disease and diabetic vessel disease. Coronary bypass grafting has been an effective strategy in these patients and will continue to be effective.

Treating ischaemic heart disease, has led to another problem of congestive heart failure which is on the rise with 30,000 plus new cases per year in Australia alone. [3] A large percentage of these patients have functional mitral valve regurgitation and are refractory to medical therapy requiring surgical intervention. A limited heart donor pool for transplantation has resulted in heart failure patients requiring other surgical treatments including the use of annuloplasty rings, the Dor procedure, direct remodelling, left ventricular assist and total artificial heart devices. All of which are significant advances in the area of heart failure surgery, improving patient mortality and morbidity. The surgical treatment of atrial fibrillation is another frontier that is in its infancy. The Maze procedure has been associated with conversion rates of up to 99%. This is far superior to the 50% of patients that will sustain a sinus rhythm with percutaneous catheter ablation or medical therapy. [4]

Those within the cardiac field state that there will be a shortage in qualified cardiac surgeons being able to combat high risk cases in the future due to inadequate training consequential of catheter-based intervention. Training programs already have a difficult time providing effective clinical training in many open procedures including valve repair, complex bypass grafts, off-pump surgery and homograft valve surgery. Technological advances will result in a further subspecialisation of the field and move away from the “general” cardiac surgeon. Small volume cardiac surgery hospitals will diminish with the future progressing towards a limited number of superspecialised cardiothoracic surgical institutions centred in metropolitan areas that are able to combat the high risk difficult cardiac cases.

Currently, at the Australian college of surgeon level, there is a push towards a combined vascular and cardiothoracic training program with cardiothoracic fellows already pursuing fellowships in vascular surgery and vice versa as the differing surgical skills required in the two fields will complement each other, better equipping the surgeon with skills to utilise modern technological devices and resulting in an amalgamation of both specialties. Countries outside of Australia, such as Germany, Canada and Japan have always had separate paths for training in Cardiovascular and Thoracic surgery. Perhaps one may see a shift towards these countries in the future.

For those who believe the cardiac surgeon is a dying breed, this is far from the truth and a mere myth. Interventional cardiologists have become more skilled and adventurous with the catheter-based technologies, but they are limited to that one approach. Cardiac surgery will expand as it encompasses newer technologies. The next generation cardiac surgeons will be equipped at complex bypass grafting, heart transplant and congestive heart failure treatment modalities, percutaneous mitral valvular repair and be equipped with endoluminal vascular surgical skills. A change from an individual treatment approach is also required in the field of cardiac medicine, with a multidisciplinary team comprising of both the cardiac surgeon and the cardiologist. At the end of the day, it is the patient’s interest that should be the centre of focus, eliminating conflicts between areas of expertise and allowing the practice of evidence-based medicine.


The author wishes to thank A/Prof C Juergens, A/Prof R Dignan and Mr PP Punjabi for fostering his appreciation of cardiac medicine. Thanks also to Prof PG Bannon and Dr N Jepson from the University of New South Wales


[1] Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106:3006–8.

[2] Australian Institute of Health and Welfare. Cardiovascular disease: Australian Facts 2011. Cardiovascular disease series. Canberra:AIHW;2011. Cat. no. CVD 53.

[3] AIHW: Field B. Heart failure…what of the future? Bulletin no. 6. Canberra:AIHW;2003. Cat. No. AUS 34.

[4] Cox JL, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud JP, DeGroot KW, et al. Current status of the Maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg. 2000;12(1):15–9.

Original Research Articles Articles

Immunisation and informed decision-making amongst Islamic primary school parents and staff

Background: The Islamic community represents a recognisable and growing minority group in the broader Australian context. Some sectors of the international Muslim community have voiced concerns about the ritual cleanliness of vaccines, and seen subsequent lower levels of compliance. Anecdotal evidence suggests Australian Muslims may hold similar concerns. Aim: This study aims to evaluate the information and knowledge with which Islamic parents and staff are equipped to make decisions about immunisation. Methods: Parents and staff at an Islamic primary school were recruited through survey forms sent home for voluntary completion. These surveys were designed to assess the sources of information and level of confidence regarding immunisations as well as highlighting personal perspectives of the participants and misapprehensions. All participants identified as Muslim parents. Results: 40.7% (n = 64) of respondents were not confident that they knew enough about vaccines to make good decisions, while 73.3% (n=115) respondents stated a personal desire for further education about vaccinations and vaccination schedules, suggesting a significant degree of uncertainty associated with the amount of information currently accessible to this cohort of the community. Qualitative responses reflected concerns associated with side effects and the halal nature of vaccines. As these responses included a perceived information gap about material risks, it raises the possibility of invalid consent. Parents obtain information from a variety of sources, the most popular being their general practitioner. However, our data suggested that the public health nurses of the shire council facilitated better knowledge outcomes than general practitioners. Conclusion: By taking the time to communicate material risks to Muslim parents, health professionals ensure confident, informed decision-making and consent.


The Islamic community presents a recognisable and growing minority group in the broader Australian context. In light of the nature of their religious fidelity, Islamic patients will bring different attitudes and knowledge to the clinical setting, requiring sensitive and appropriate medical attention. [1] A working knowledge of the core tenets of Islam allows clinicians to provide culturally relevant information to facilitate informed consent and decision-making. For example, the prohibition in Islam against receiving pork and other unclean meat products (“haram”), and the inclusion of derivatives from these in some surgical and pharmacological interventions can be an important consideration to convey, and potentially damaging omission to make in a consultation. [2]

While there is a corpus of published information pertaining to Muslim cultural considerations in medical and especially nursing practice in Australia, we identified a gap in the literature in relation to attitudes and behaviours towards immunisation. Some isolated voices in the large religious grouping of Islam have voiced major concerns about haram or unclean content in vaccines: Dr Abdul Majid Katme [3], of the ‘Islamic Medical Association of Britain’ is reported as “urging British Muslims not to vaccinate their children against diseases such as measles, mumps and rubella because they contain substances making them unlawful for Muslims to take.”

Concerns have been raised in the broader medical fraternity in relation to how statements such as this have influenced Islamic patient’s compliance with immunisation, with data demonstrating a decrease in immunisation rates in majority Muslim countries such as Nigeria [4] and Pakistan [5], where leaders and clerics have made complex claims against the safety of vaccines. The level of non-compliance that resulted from these attitudes has set back efforts to eradicate polio worldwide. [6] In response, Warraich [7] made calls for further study into Muslim populations’ attitudes towards vaccination. In the Australian context, Zwar [8] mentions that there is “anecdotal evidence that Australian Muslims may share the concerns and fears about vaccination safety” held by their brethren overseas.

Having identified the need for more data from the Muslim Australian perspective on vaccines, we endeavoured to assess the information sources and knowledge of the members of one diverse Islamic community, a primary school. Focussing on the degree to which parents are capable and confident to make informed consensual decisions about their child’s immunisations, we endeavoured to determine the extent to which the data reflects trends of unease, and to provide some insight into what gives rise to such concerns.


This project received ethics approval from the Community Based Placement Program conveners, mandated by the Monash University Human Research Ethics Committee (MUHREC) to approve low impact research.

A mixed methods design was employed. A survey, designed by the authors, was used to collect qualitative and quantitative data anonymously from participants, who were parents of the students who attended the Australian International Academy King Khalid Campus primary school, and members of staff who were parents (irrespective of where their children attended school). Conducted as part of a community based health promotion project, the school agreed to host the researchers and provide supervision on the condition that sensitive questions pertaining to demographics or religious sensitivities were not explicitly asked.

Participants were recruited through one of two methods: the first being hand delivery of surveys to staff with children of their own (thereby parents themselves), and the second through the bi-monthly newsletter received by every family within the school community. Surveys were accompanied by corresponding consent documents and explanatory statements. Consent forms were received before inclusion of data. A total of 300 surveys were distributed to potential participants.

Key measures of interest were the information sources and knowledge with which these parents are equipped to make decisions surrounding vaccinations for their children and themselves. Thirteen survey questions were organised into three domains: “Obtaining Information” asking about where their knowledge about vaccines was sourced, “Concerns” which assessed for misapprehensions and misinformation about vaccines, and “Vaccines” which invited them to indicate how confident they felt in the process and their level of understanding, and their desire for more education on vaccines. At the end of those questions a single space was given where respondents could write any comments or questions sparked by the survey. Additionally, individuals surveyed were asked to include the year level of their eldest child in order to allow comparison of data across a spectrum of child age as an indicator of length of parent exposure to the immunisation process. No other demographic data was collected at the request of the school.

Descriptive statistics were used to analyse responses, with bivariate analysis of statistics to assess correlations between sources of information, age of eldest child and degree of confidence and knowledge about vaccinations. The narrative provided as feedback was also analysed for themes.

Data were analysed using Microsoft® Excel 2003. Qualitative responses were examined for recurring themes and considered in conjunction with statistical evidence as a means of determining study results.


The researchers received a total of 157 validly completed survey forms out of the 300 distributed to the parents and staff of the school, a 52.3% response rate. No differentiation was made between parent or staff member status within the school as all participants were Muslim parents. In accordance with state legislation, all children of respondents were fully immunised at the time of enrolment. 15 respondents chose to use the space provided in the survey to give qualitative feedback, comments from which are interspersed below into the relevant domains.

Obtaining information

Participants of the study indicated that knowledge and guidance regarding immunisation were gained through a multitude of sources. The research confirmed that all participants had undertaken information seeking regarding childhood vaccination.

Surveys illustrated that 80.9% (127/157) of participants had used more than one source to assist in the decision-making process; while only 19.1% (30/157) had relied solely upon a single source. Of the 30 who had based their perspectives upon one source of information, 90.0% (27 out of 30) had consulted a healthcare professional – general practitioner (GP) or nurse, while the remaining 10% (3 out of 30) all received input from the local council. Flyers, (3.2%), friends (20.4%), internet (22.9%) and media (26.1%) were all used, in conjunction with other resources, to aid in the enhancement of their vaccination knowledge. Results indicated that 86.0% of all participants had sought education from GPs making them the most commonly accessed source. “I go with what my local doctor tells me to do, which I assume was the best thing to follow,” was the feedback received from one participant.


One respondent commented: “I don’t believe enough information is provided to families about each vaccination, what it does and the side effects.” When asked about possible health concerns associated with vaccinations, 50.0% of all respondents (78 out of 157) were not aware of the possible side effects of vaccinations. In fact, 75.8% (119 of 157) of participants stated that they were concerned that vaccinations would have adverse outcomes on their children’s health.


“I wish there was more information about it as we took it as it is a must and the government encourages it,” remarked one respondent. Only 60.3% (93 of 157) of parents were sufficiently comfortable with their level of knowledge to make an informed decision pertaining to their child’s immunisations. This suggested that almost 40.0% (64 parents and staff) were not confident in their ability to make an informed decision for themselves or their family. Furthermore, 73.3% (115 of 157) stated a personal desire for more information about vaccinations and vaccination schedules.

When comparing knowledge confidence between those who received information from a GP versus those who received their information from the shire, council nurses, the latter group had slightly better outcomes than GPs (73.5% to 71.1%). The value of increased engagement with council nurses was highlighted in our report recommendations.

The constituents of vaccines were also highlighted as a concern in the qualitative responses: “I wanted to know what the vaccines were made of.” In particular, the halal status of vaccines was brought up in this comment and others: “Hopefully you could work on making a vaccine that will be significant with our religion background which is Halal Vaccine (without pork products).”


This research represents a sizable study into the Australian Muslim community’s approach to immunisation: the largest published study involved only 22 informants belonging to one ethnic group. [9] We valued the opportunity to undertake our fieldwork in a school environment, because it provided a snapshot of the broad cross-section of individuals who make up this community, and the attitudes and knowledge of those who make decisions on vaccinations. In the future, it would be useful to explore how patient-centred factors, such as education and language impact on decision-making.

Education and side effects

The emergent theme was that the greatest concerns could be traced back to accessing relevant information about vaccination, with 73.3% of respondents having stated a personal desire for further education about vaccinations and vaccination schedules. This suggests some dissatisfaction with respect to their own levels of knowledge around vaccines and the education provided about vaccines as part of their decision-making. As a result of this disparity our research saw a startlingly high proportion of respondents (75.8%) concede concerns that vaccinations would have adverse outcomes on their children’s health. Half of all respondents also admitted ignorance with regards to potential vaccine side effects in the survey.

Side effects are not uncommon with vaccines, and a sure cause for concern amongst parents. The degree to which the study findings illuminated participant’s limited existing knowledge pertaining to side effects involved with vaccination, both qualitatively and quantitatively, indicates a dereliction of duty on the behalf of the general practitioners administering vaccines. This is an example of a process-centred barrier to informed consent. [10]

One of the consequences of this lack of knowledge by decision-makers is evidenced by the 40.76% of respondents who did not feel well equipped to make good decisions for their families. This reflected in comments such as this from one respondent: “I go with what my local doctor tells me to do, which I assume was the best thing to follow,” sentiments echoed across the world. [11] We propose that this lack of confidence, combined with a suggested sense of a culture of paternalism, remains prevalent in the doctor-patient interaction with regards to vaccine decision-making in this community, hampering the quality of consent given.

Analysis of the levels of confidence in participants’ knowledge showed that those participants who had received information from council nurses had more confidence in their decision making about vaccines than those whose main source was their general practitioner. This highlights a need for patients and general practitioners to partner with these valuable community nurses to enhance patient education and confident decision-making.

Material risks with respect to immunisation in Islam

As Young states: “In a health-care setting, when a patient exercises her autonomy, she decides which of the options for dealing with her health-care problem (including having no treatment at all) will be best for her, given her particular values, concerns and goals.” [12] Practicing Muslim patients place great value on the consumption only of those things deemed “halal” (ritually clean) and avoiding those things which may be unclean (“haram”). Pork is considered ritually unclean in Islam; and if a particular intervention contained pork-derived materials, this could reasonably constitute a material risk to a Muslim patient. [13] For example, in the British context, in a study of Muslim patients, 42% indicated that they would not take any medical interventions unless they were sure it was halal. [14]

Various vaccines, including MMR and the Hib vaccines, compulsory for Muslim pilgrims undertaking the Hajj [15] contain or involve porcine products in their manufacture, and are thus technically unclean. However, Islamic judicial and medical bodies embracing the value of beneficence have created an exemption for such products in the interests of public health. [16] The British statistics, as well as the findings of our study demonstrate that practicing Muslim patients harbour concerns about the halal nature of vaccines, and as such doctors need to be aware of concerns surrounding the prohibition and be able to effectively communicate the facts and exemptions of vaccine composition and manufacturing. This should include the referral of a patient on to more comprehensive sources should the need arise.


This investigation was undertaken to explore decision-making immunisation. Our study of this Islamic school community clearly demonstrated a perceived information gap with the information presented surrounding vaccinations and a consequent lack of confidence in their decision-making process. Qualitative and quantitative feedback obtained in this study provided evidence that the current information provided on vaccination is not catering to the needs of this Islamic community.

One limitation of our investigation was lack of access to a non-Islamic control group as a point of reference for the broader Australian community’s attitudes and knowledge. A broader information base would have clarified components of vaccine education generic to all communities and allowed tailoring education programs to the needs and concerns of individual communities. With respect to the Muslim community, there is scope for further inquiry into attitudes and awareness of general practitioners and nurses about the halal status of immunisations and other medical interventions, to triangulate the data and provide a basis for enhanced vaccine provider education.

The present study, however, provides evidence to encourage an increased role for council nurses in parental vaccine education, as well as identifying the desire of some Muslim parents for education on and confirmation of the ritual cleanliness of vaccines. By taking the time to inquire about and educate parents on all material risks, health professionals ensure confident, informed decision-making on the part of parents and a safe, healthy future for our children.


We are grateful for the assistance of our Academic Advisor, Monica Mercieca, the support of our Field Educators, Ms Rabia Jones and Ms Angela Florio, and all the staff and students of the Australian International Academy – King Khalid Campus.

Conflicts of interest

None declared.


M Bray:


[1] Mohammadi N, Evans D, Jones T. Muslims in Australian Hospitals: clash of cultures. Int J Nurs Pract 2007;13(5):310–5.

[2] Easterbrook C, Maddern G. Porcine and bovine surgical products: Jewish, Muslim and Hindu perspectives. Arch Surg 2008;143(1):366-70.

[3] Elkins R. Muslims urged to refuse ‘un-Islamic’ vaccinations [internet]. 2007 Jan 28 [cited 2010 Aug 15]; Available from:

[4] Kapp C. Surge in polio spreads alarm in northern Nigeria. Lancet 2003;362(1):1631.

[5] Ahmad K. Pakistan struggles to eradicate polio. Lancet Infect Dis 2007;7(4):247.

[6] Tackling negative perceptions towards vaccination. Lancet Infect Dis 2007;7(4):235.

[7] Warraich H. Religious opposition to polio vaccination. Emerg Infect Dis 2009;15(6):978.

[8] Zwar N. Polio makes a comeback. Australian Doctor [internet]. 2006 Jan 9 [cited 2010 Aug 15]; Available from:

[9] Brooke D, Omeri A. Beliefs about childhood immunisation among Lebanese Muslim Immigrants in Australia. J Multicult Nurse Health 1999;10(3):229-36.

[10] Taylor H. Barriers to informed consent. Semin Oncol Nurs 1999;15(2):89-95.

[11] Marfé E. Immunisation: are parents making informed decisions? J Spec Pediatr Nurs 2007;19(5):20-2.

[12] Young R. Informed Consent and Patient Autonomy. In: Kuhse H, Singer P, editors. A Companion to Bioethics. Oxford: Wiley-Blackwell; 2010. P.379-89.

[13] Eldred BE, Dean AJ, McGuire TM, Nash AL. Vaccine components and constituents: responding to consumer concerns. Med J Aust 2006;184(4):170–5.

[14] Bashir A, Asif M, Lacey FM, Langley CL, Marriot K, Wilson A. Concordance in Muslim patients in primary care. Int J Pharm Prac 2001; 9(1):78.

[15] Saudi Ministry of Hajj. Riyadh: Hajj 2010 Health Requirements [Internet]. 2010 [cited 2010 Oct 16]. Available from:

[16] Islamic Organization for Medical Sciences. The use of unlawful or juridically unclean substances in food and medicine [Internet]. 2009 [cited 2010 Aug 15] Available from:

Original Research Articles Articles

Recognition and response to the clinically deteriorating patient

Background: Early recognition of clinical deterioration has been associated with a lower level of intervention and reduced adverse events. A widely-used approach in Australia is the Medical Emergency Team (MET) system. Research suggests having a multi-faceted approach to patient monitoring such as Modified Early Warning Score (MEWS) improves early review. Aim: To assess MET call initiation and response. Objectives: (1) In adult patients who have a MET call, was the call made immediately after meeting MET criteria? (2) In adult patients who have a MET call, was a MEWS scored > 4 reached prior to the call? Methods: 20 adult patients (> 18 years) that had a MET call made on acute medical or surgical wards at a Western Australian outer metropolitan secondary teaching hospital between 1 January and 30 April 2011 were selected. Records and observations were reviewed to determine whether MET call response was made immediately, and if MEWS were used, whether earlier review may have occurred. Results: Adjusted MET call response times (observations < 180 minutes) revealed 20% of patients did not have MET call made immediately (< one minute) and did not meet the standard. Ten percent warranted an earlier MET call and 25% achieved MEWS criteria > four within 180 minutes before MET call. Identification and responding to the patients with MEWS > 4 may have prevented 25% of MET calls. Conclusion: While all MET calls should have an immediate response, this is not always achieved. Implementation of MEWS may improve recognition and response to the deteriorating patient.


Early recognition of clinical deterioration, followed by prompt response is associated with a lower level of intervention to stabilise patients and reduced adverse events. [1-3] Effective recognition and response to deterioration requires defined observation parameters, trained staff, appropriate equipment, policies, escalation protocol, communication and rapid response. [4] Adverse patient outcomes impact on the patient and health system, such as increased length of stay, unplanned return to theatre, increased morbidity, mortality, decreased bed availability and inefficient re-allocation of limited health resources. [5,6]

Early recognition and warning systems aim to identify and intervene before a patient deteriorates, reducing adverse outcomes. A widely-used approach in Australia is the Medical Emergency Team (MET) system, which includes staff education of the dangers of physiological instability, defining MET call criteria, improving communication and establishing policies, procedures, and systems for immediate response to patient deterioration. [7]

This study was conducted at a Western Australian outer metropolitan secondary teaching hospital (de-identified for publication and referred to herein as “health service”) to look at recognition and response to the clinically deteriorating patient. The health service uses the MET call system. According to MET Call Policy [8], calls should be made as soon as a patient meets any MET call criterion (Figure 1). An internal audit [9] looked at observation tools, adherence to protocol, documentation and response. Results revealed 62.5% of patient deterioration were recorded and 25% of deterioration were not acted upon (i.e. no MET call or escalation for review). In addition multiple forms were used to record observations, resulting in gaps on charts, reducing the ability to identify trends. These findings are similar to a randomised controlled study where the MET call system was introduced in twelve of 23 Australian hospitals. Researchers [7] found that when there were documented physical abnormalities and MET call criteria were reached, MET was called for only 30% of patients prior to unplanned intensive care unit (ICU) admissions. Furthermore, the MET system increased emergency team calling but did not substantially alter occurrence of cardiac arrest, unplanned ICU admission or unexpected death.

The Australian Commission on Safety and Quality in Healthcare has identified recognising and responding to clinical deterioration as a key issue. [4] The health service was introducing the COMPASS Modified Early Warning Score (MEWS) System (Figure 2 for calculation and Figure 3 for response). [12] Researchers reviewed outcomes of COMPASS and concluded that having a multi-faceted approach to patient monitoring improved early medical review following clinical instability. [11] The COMPASS system was being implemented to consolidate recordings and allow for a score (MEWS) to be calculated to flag early deterioration in addition to existing MET call processes.

The topic was chosen to enhance understanding of METs and early warning systems, including impact on outcomes and compliance with MET policy. The aim was to assess MET call initiation and response (process of care).


1. In adult patients who have a MET call, is the call made immediately after meeting MET criteria? (Compliance with policy).

2. In adult patients who have a MET call, was MEWS > 4 reached prior to the call? (MEWS > 4 requires medical review which may prevent MET call).



A Western Australian outer metropolitan secondary teaching hospital with a total of 13,070 medical and 4,558 surgical admissions in 2011 (average 1,089 medical and 380 surgical admissions per month). On general surgery areas, there is medical cover during the day and an on call consultant 24 hours. On general medical areas, there is medical cover during the day, Resident / Registrar cover after hours until 22:00 and on call consultant 24 hours. Emergencies on both wards are covered by the MET. The health service has one MET and one backup team.


The MET Call Policy is the standard for MET calls (Figure 1). [8] One hundred percent of MET call cases must have a documented response immediately after an observation that meets MET call criteria (Figure 1).

There is Level III-1 NHMRC evidence for MERIT Study Investigators who found MET calls were made for 30% of patients before unplanned intensive care admission and equivocal improvements in outcome based on MET call alone. [7] There is Level III-3 NHMRC evidence for findings on the effectiveness of COMPASS. [11]

Case Definition

A case is any adult patient (> 18 years) on the acute medical or general surgical ward at the health service that had a MET call made between 1 January and 30 April 2011.

Patient Selection

MET calls are documented in the medical record. The Resuscitation Educator maintains a log of all MET calls. Only MET calls that occurred in patients aged 18 years and over on acute medical or surgical areas were chosen. In patients with multiple MET calls in one admission only the first MET call was reviewed and patients with altered MET criteria were excluded. A sample size of 20 was selected due to time constraints in reviewing multiple forms and calculating MEWS by transcribing observations using a collection tool.

Sample Size and Analysis

A pilot study was conducted on three records from March 2011. Descriptive data were used for analysis. Confidence intervals (CI) were calculated using the modified Wald method. [15]

Data Collection

Data were obtained from medical records selected as per Patient Selection. The MET calls log was obtained for 1 January to 30 April 2011. MET calls for non-medical and non-surgical patients, patients less than 18 years and piloted records were removed. The first 20 MET calls where medical records could be located were chosen.

The Author collected data by reviewing medical records and records checked for altered MET criteria statements. Observations < 180 minutes to the MET call were checked on all forms in the admission. Within 180 minutes was chosen, as MET call criteria requires urine output over 3 hours to be checked. MEWS was calculated to the observation greater than but closest to 180 minutes before the MET call using MEWS Collection Tool. Data were entered into Microsoft Excel using data collection tool and dictionary. Demographic, exposure and outcome variables are listed in Figure 4. Missing, conflicting and ambiguous data were recorded as ‘missing’.

Other Issues

Cases were de-identified. Electronic data were password protected and collection tools stored securely. Identifying staff and patient information were not recorded, patient interaction was not required and patient consent was not necessary as per NHMRC. [16] Stakeholders included staff involved in initiating or attending METs and Executive. Clinical Quality and Safety Committee approval was obtained.


Twenty of the 36 adult medical and surgical patients who had MET calls during January to March 2011 were selected (55.6% of MET calls). Age range of patients selected was 29 to 89 years, with a mean age of 74.7 years (median 79 years). In comparison, age range for the 36 patients from which patients were sampled was 29 to 92 years, with a mean age of 72.3 years and median 77.5 years. There were no patients with altered MET criteria.

Reason for MET call is summarised in Table 1. Five patients (25%) achieved two MET call categories, while no patients reached three or more categories. The most common reason for MET call was circulation problem (i.e. pulse rate < 40 or > 130 beats per minute (bpm)), with seven patients (35%) having MET call for this reason.

MET call response times varied between zero and ten minutes (Figure 5). Seventeen patients (85%) had a response within and including one minute. Three patients had a delay exceeding one minute (15%). The mean response time was one minute and median zero minutes.

Two patients (10%) were identified as reaching MET call criteria in observations before the one that resulted in MET call. The delay was 14 and 160 minutes, with an average of 87 minutes (Table 2). The patient with a 14 minute delay had a further four minute deferral after the second observation that achieved MET call criteria. The patient with 160 minute delay had the MET call made immediately after the subsequent observation that achieved MET call criteria. Consequently four patients (20%) had an adjusted MET call response time greater than one minute (mean 9.5 minutes, range 0-160 minutes, median 0 minutes, 95% CI 0.0749-0.4218).

For two patients (10%), it could not be determined whether an earlier observation fell into MET call criteria. One patient had missing progress notes and observation chart. The other had documented deviated observations in the progress notes without time recorded. It could not be ascertained whether this occurred within 180 minutes of the MET call.

Five patients (25%) achieved a calculated MEWS > 4 within the last observation greater than but closest to 180 minutes of the MET Call (Table 3). The 95% CI extends from 0.1081-0.4725. Of these, four were < 180 minutes of the MET call. Time period between MEWS > 4 and MET call ranged between five and 210 minutes (3 hours 30 minutes), with a mean of 113 minutes.

Five patients (25%) were discharged the same day as the MET call (Table 4). Of the five patients, one patient deceased (5%) and four patients (20%) were transferred to an acute hospital for further management (i.e. Royal Perth or Sir Charles Gairdner Hospitals).


Adjusted MET call response times (inclusive of observations < 180 minutes) revealed 20% of patients did not have MET call made immediately (< one minute) and did not meet the standard. Ten percent warranted an earlier MET call and 25% achieved MEWS criteria > four within 180 minutes before MET call. Identification and responding to the patients with MEWS > 4 may have prevented 25% of MET calls. The CI of 0.1081 to 0.4725 warrants further study with increased sample size.

Twenty percent may not have met the standard due to delayed MET call response (e.g. hesitation or watchful waiting), inexperience, not recording altered MET criteria, and inaccurate documentation of times on the Resuscitation Record. The Resuscitation Record contained pulse rate > 140 bpm whereas hospital policy states pulse rate > 130 bpm warrants MET call. While this did not appear to affect data, it may create confusion for staff.

Ten percent of patients required earlier MET call, showing an improvement to a previous audit [9] where 25% of deterioration were not acted upon. While not achieving the standard, results are better than those found by MERIT Study Investigators where only 30% of patients admitted to the ICU had a MET call. [7] This study looked at various patients, not just ICU admissions which may contribute to this variance. Besides revealing current practice, the study provides a baseline for evaluation of COMPASS and effectiveness of MEWS post-implementation in achieving the standard.

Twenty-five percent of patients were discharged on the same day as the MET call. One patient who achieved a MEWS > 4 was discharged the same day and earlier identification with MEWS may have allowed for earlier planning or transfer. The deceased patient had an unpreventable condition.


  • Patients without MET call may have reached calling criteria. These were not included as the audit looked at MET calls made. Failure to meet the standard may be higher.
  • Observations in the preceding 180 minutes were reviewed. Patients may have had observations warranting MET call earlier than this.
  • Not all observations used in MEWS calculation were recorded in every observation set. MEWS > 4 may have been reached yet could not be determined.
  • Adult surgical and medical patients were included. Responses for other groups may differ.
  • Sample was determined from the MET call log. Missing forms or accidental omissions during logging of cases may have affected accuracy.
  • Audit period included January which may include increased agency and relief staff. This was intentional as staff should respond to and be familiar with MET call processes.
  • Patients with multiple MET calls only had the first MET call reviewed.
  • This was a single site and results may not be externally valid.
  • While data collected by the author was pre-recorded in the medical record, the author was not blinded to the study aims.

Results, feedback and recommendations were communicated with stakeholders at the health service through a summary report which was distributed by email, followed by presentation of findings and feedback session. Recommendations were as follows:

  • Record observations on a single form.
  • MET call policy requires a definition of “immediate” (e.g. less than one minute) to provide clarification and measurable outcome.
  • Reiterate to staff the importance of accurate documentation (e.g. times).
  • Conduct research to assess patient outcomes and compare with other hospitals.
  • Re-audit following MEWS Observation Chart implementation. Compare MET call response with other Australian hospitals that utilise COMPASS.
  • Obtain further stakeholder feedback on existing practice and potential for improvement (e.g. verbal discussion, email, team meetings).
  • Adjust pulse rate on the Resuscitation Record to > 130 bpm to reflect hospital policy.

Recommendations may be applicable to other health services utilising MET call system and MEWS, particularly defining what “immediate response” is with a timeframe to allow for review of compliance. Further research could review a selection of patients regardless of whether MET call was made and review observations to determine whether MET call should have been made. While this is a time consuming task, hospitals utilising MEWS charts will make this process easier.


While all MET calls should have an immediate response, this is not always achieved. Implementation of MEWS or secondary warning system may improve recognition and response to the clinically deteriorating patient. Responding to a patient at an early stage in their deterioration may reduce adverse outcomes and use of resources. To improve review and audit of response to clinical deterioration, further clarification of what “immediate” means is required in the standard.


Ms Deborah Goddard, Department of Health Western Australia

Conflict of interest

None declared.


G Parham:


[1] Australian Commission on Safety and Quality in Healthcare. National Consensus Statement: Essential Elements for Recognising and Responding to Clinical Deterioration [Internet]. Sydney: ACSQHC; 2010 [cited 2011 Mar 13]. Available from:$File/

[2] National Institute for Health and Clinical Excellence. Acutely Ill Patients in Hospital: Recognition of and Response to Acute Illness in Adults in Hospital [Internet]. London: NICE; 2007 [cited 2011 Mar 13]. Available from:

[3] Hillman KM, Bristow PJ, Chey T, Daffurn K, Jacques T, Norman SL, et al. Antecedents to hospital deaths. Intern Med J. 2001;31: 343-8.

[4] Australian Commission on Safety and Quality in Healthcare. Recognising and Responding to Clinical Deterioration: Background Paper [Internet]. ACSQHC; 2008 [cited March 2011]. Available from:$File/

[5] Dacey MJ, Mirza ER, Wilcox V, Doherty M, Mello J, Boyer A, et al. The effect of a rapid response team on major clinical outcome measures in a community hospital. Crit Care Med. 2007;35(9):2076-82.

[6] Devita MA, Bellomo R, Hillman K, Kellum J, Rotondi A, Teres D, et al. Findings of the first consensus conference on rapid response teams. Crit Care Med. 2006;34:2463-78.

[7] MERIT Study Investigators. Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial. Lancet. 2005:365:2091-7.

[8] [name deleted] Health Service. Practice Standard for the Management of Medical Emergencies and Cardiorespiratory Arrest [Hospital Work Practice]. WA: [name deleted] 2011 Jan.

[9] [name deleted] Health Service. Audit of Observational Tools [Unpublished Audit Paper]. WA: [name deleted] 2010 Jul.

[10] [name deleted] Health Service. Practice Standard for the Management of Medical Emergencies and Cardiorespiratory Arrest [Hospital Work Practice]. WA: [name deleted] 2011 Jan. P.6.

[11] Mitchell IA, McKay H, Van Leuvan C, Berryd R, McCutcheond C, Avarda B, et al. A prospective controlled trial of the effect of a multi-faceted intervention on early recognition and intervention in deteriorating hospital patients. Resuscitation. 2010;81:658-66.

[12] COMPASS. Pointing You in the Right Direction – Adult (2nd ed.). Australian Capital Territory: ACT Publishing; 2010.

[13] COMPASS. Pointing You in the Right Direction – Adult (2nd ed.). Australian Capital Territory: ACT Publishing; 2010. P.8,9.

[14] COMPASS. Pointing You in the Right Direction – Adult (2nd ed.). Australian Capital Territory: ACT Publishing; 2010. P.11.

[15] Agresti A, Coull BA. Approximate is better than “Exact” for interval estimation of binomial proportions. Am Stat 1998:52:119-26.

[16] National Health & Medical Research Council. When does quality assurance in health care require independent review. Canberra: NHRMC; 2003.

Review Articles Articles

Vitamin D deficiency in the elderly: How can we improve rates of screening and supplementation in General Practice?

Aim: Vitamin D supplementation reduces falls and fractures in the elderly, yet screening and supplementation rates are generally inadequate. We therefore investigated whether rates of screening and supplementation could be improved through a brief, general practitioner (GP)-focussed, educational intervention. Methods: Clinical audits of vitamin D screening and supplementation in elderly patients attending a rural general practice were conducted before and after a GP educational intervention. Results: The simple GP educational intervention resulted in both vitamin D screening (11.1% versus 5% – 2 year period: and 6.11% versus 3.38% – 3 month period) and supplementation rates ≥ 700IU cholecalciferol daily (10% versus 5% – 2 year period; and 4.44% versus 0.97% – 3 month period) approximately doubling in elderly patients. Discussion: This preliminary study suggests that simple, cost-eff ective GP-focussed interventions can significantly improve vitamin D screening and supplementation rates in elderly patients, thereby potentially improving health outcomes in terms of falls and fractures in this ‘at risk’ population.

Review Articles Articles

Australia’s experience of Bordetella pertussis and a proposed national preventive strategy into the future

Elimination of Bordetella pertussis, an exclusively human pathogen, has proven to be elusive in Australia despite universal vaccination. Australia has witnessed a resurgence of pertussus particularly in infants less than 6 months old, and adults over 20 years old. This resurgence has resulted in high notification rates, morbidity and mortality in the two age groups. This may be due to the largely asymptomatic presentation in young infants and adults, as well as sub-optimal immunity due to lack of development, or waning immunity in adults. Various levels of prevention need to be identified so that a national preventative strategy may be sought to reduce the impact of pertussis infection amongst Australians in the future.

Pertussis is an acute illness caused by Bordetella pertussis, a Gram-negative coccobacillus with exclusive affinity for the mucosal layers of the human respiratory tract. Pertussis is highly contagious and spread by air borne respiratory droplets when an infected person coughs or sneezes, or via direct contact with secretions from the nose or throat. [1] Following an incubation period of 9-10 days, patients usually present with an irritating cough that gradually becomes paroxysmal and lasts for 1-2 months. [2] However, in adults and older children, the diagnosis of pertussis is often subclinical and delayed due to an absence of classical symptoms, resulting in potential transmission of infection for several weeks. [3] In Australia, the preferred methods for laboratory diagnosis of pertussis are culture and polymerase chain reaction (PCR), and it is recommended in most cases that both tests be performed. However, there is a trend to move towards PCR, which provides rapid results, and is more sensitive in previously immunised individuals, and more likely to be positive in patients who have received antimicrobial treatment than culture. [1-4]
Since the 1950s, effective pertussis immunisation programs have reduced hospitalisations and deaths in Australia dramatically. [4] Currently, the acellular pertussis vaccine (DTPa) is safer and more effective than whole cell pertussis vaccine (DTPw), which is no longer used in Australia. [1] DTPa vaccines are associated with lower incidence of fever and local reactions than DTPw, and serious side effects are rare. [1,6] DTPa is free for Australian children at 2, 4 and 6 months of age, with a booster available at 4 years and during adolescence. [5] Despite the availability of vaccines in Australia, it remains a challenging disease to control among two age groups: under the age of 6 months who suffer the most severe infections and highest mortality, and those older than 20 years. [1,6] Adolescents and adults are an important reservoir for infection as they are capable of transmitting pertussis to infants who were too young to have received two or more DTPa vaccines required for optimum protection. [1]
In Australia, pertussis cases are notifiable under each state and territory Public Health Act. [4] There were 34,490 pertussis notifications received by the National Notifiable Diseases Surveillance System (NNDS) in 2010, the highest recorded since 1991 (Figure 1). A general increase in endemic peaks have occurred every 4-5 years since national notifications became available in 1991, occurring in 1997 (12,232 notifications), 2001 (9,530 notifications), 2005 (11,168 notifications) and 2010 (34,490 notifications). A clear seasonal pattern exists, with the highest number of notifications in the spring and summer months (between August and February) each year between 1993 and 2010. [2] In terms of age specifi c pertussis incidence rates, children less than 1 year old had the highest annual notification rate in all of the analysed years, and high rates were also observed in 5-9 years olds, with a peak notification rate in 1997 of 194 cases / 100,000. [4] Adults aged 20-59 years accounted for 56% of notifications, with elderly patients aged 60 years and over accounting for 15% of notifications in 2005 (Figure 2). Recently, there has been a rise in notification rates in the 20-59 year old age group, and in those over the age of 60, increasing by 57% and 17% respectively in 2010. This is in contrast to the relatively steady annual rates previously seen in these age groups between 1993-2003.
Hospitalisations, which refer to a period of time when a patient is confined to a hospital, followed a similar pattern to notifications (Figure 1) with a total of 1,478 separations recorded during 1998-2008 (Figure 3). Of these separations, they were most prominent in the 0-4 age categories, with 967 separations (Table 1). Peak separations occurred in the period of 2001-2002 (258 separations), 2004-2005 (222 separations) and 2007-2008 (250 separations).
There were 9,338 hospital bed days recorded for all ages during 1998-2008, with the highest number of hospital bed days toward the 0-4 year old group. Total hospital bed stays peaked during 2001-2002 (1,628 days) and 2004-2005 (1,640 days). Over the two years 2003-2004, two deaths were recorded where pertussis was the underlying cause, with both occurring in 2004; one case was 1 month of age and the other a 95 year old patient. [2] During 1993-2002, there was a total of 16 deaths attributed to pertussis, of which 15 (94%) occurred in infants less than 6 months of age. [6]
The latest study by Australian Department of Health and Ageing showed that between 2003-2005, only 37% of infants less than 6 months were fully vaccinated, and 12% partially vaccinated. [2,4] There are proposed explanations for increasing pertussis rates seen amongst infants in the less than 6 months of age group. Two or more doses of a pertussis-containing vaccine appear to be needed for protection, and infants less than 6 months of age are likely to be too young under Australian immunisation schedules to have reliably received two or more doses. [3] It is also likely that adults, particularly parents, are a significant source of infection to infants. Regarding individuals aged 20 and over, it is likely that increased notifications are related to greater use of serology as a diagnostic tool, and an ageing population. [4,8]
Also, waning immunity following infant vaccination and reduced opportunities for boosting immunity due to reduced circulation of pertussis may also contribute to increased susceptibility to pertussis infection and disease in the 20 years and over population. [3,8]
Risk factors
Understanding the risk factors for pertussis infection is essential to target areas of concern, and to provide a skeleton for drafting a national preventative strategy. They include:

  • Infants and children who are not immunised yet. In infants, the first dose of vaccine is immunogenic only from the age of 6 weeks, thus infants less than 6 weeks are at the highest risk of pertussis infection, often from the parents. [1-6]
  • Infants under 12 months old. Infants are particularly prone to infection prior to receiving the first two doses of DTPa. Adolescents and adults are an important reservoir for infection as they are capable of transmitting pertussis to infants. [1] In addition to increased susceptibility of acquiring infection, infants are also most at risk of developing severe complications, such as apnoea, bacterial pneumonia, pulmonary hypertension and cor-pulmonale. [5,10]
  • Adolescents aged between 12-17 years. Immunity, whether from immunisation or past history of Bordatella pertussis infection, decreases after approximately 6-10 years, resulting in renewed susceptibility to infection. Thus for most adolescents, if they do not receive a booster shot during adolescence, they are at risk, as their last dose of DTPa would have been at 4 years of age in Australia. [1-3,7,9]
  • Living in the same house or working in close contact with someone infected with Bordatella pertussis. Studies have demonstrated that households with members who have culture-positive Bordatella pertussis were more likely to have greater secondary spread. Hence, proximity is an important predictor of household and community-aquired infection, with adolescents being at higher risk compared with other age groups. [13] Additionally, adults working with young children, especially childcare workers and healthcare workers in contact with infected infants are at a higher risk of contracting Bordetella pertussis infection. [1]
  • Persons with immunodeficiency and other underlying medical conditions. These include patients who have congenital or acquired immunodefi ciency, cystic fibrosis, chronic heart failure, diabetes and chronic lung disease.
  • Indigenous Australian Infants. One study demonstrated that 52% of pertussis hospitalisations in Indigenous infants occurred at 0-2 months of age, and rates in these indigenous infants were signifi cantly higher in remote areas. Also, indigenous infants had higher hospitalisation rates and were more frequently delayed of vaccination than age matched non-indigenous infants. [14]

Prevention activities
When thinking about prevention in population health, there is consideration towards four types of prevention:

  • Primordial Prevention: Avoid the emergence and establishment of ‘upstream’ factors such as social, cultural and economic factors that contribute to increased disease incidence.
  • Primary Prevention: Preventing disease from occurring in the first place; to reduce the incidence of disease. [15]
  • Secondary Prevention: Reducing morbidity and mortality by improving the outcome of disease (such as early diagnosis and treatment) that has already developed. [15]
  • Tertiary Prevention: Reducing the progress or complications of disease and implying better rehabilitation or quality of life in the longer term. [15]

Table 2 outlines how these different types of prevention could be implemented in Australia in the future.
A national preventative strategy
A national preventative health strategy requires effective health promotion programmes. Health promotion is the process of strengthening the capability of individuals to take action and the capacity of communities to act collectively to exert control over the determinants of their health. [19]
Program Planning
Target Populations: Epidemiological and demographic information suggests that infants aged less than 6 months are at the highest risk of severe pertussis disease due to partial immunisation. Also, there is an increasing number of notification s in adults aged 20 years and over. [1] These two age groups could be extensively targeted as they are both a community need and are perceived as priority for intervention.
Vaccination Timing: There is evidence to suggest inadequacy of vaccination programs which provide doses at 2, 4, and 6 months, 4 years and in adolescence. There may be a role for earlier vaccination in order to protect those under 6 months of age. Furthermore, there may also be a role for the inclusion of those over the age of 20 in the national immunisation programme, as well as health care and childcare workers. Moreover, investment in screening, surveillance and patient education should be recommended.
Resource allocation: There is a need to mobilise resources. There may be a role for lobbying national and state governments to devote a greater proportion of the national budget to health care and disease prevention. Furthermore, there may be a role for the private sector (e.g. pharmaceutical companies) to also invest further in this disease in the form of vaccines, treatments, educational materials and awareness strategies. Human resources must also match financial resources, with appropriate medical staff providing increased vaccination and health promotion on this issue. Finally, building sustainable relationships between different bodies is key to the long-term success of health promotion, e.g. between Medicare Australia, the Australian Medical Association, public hospitals, pharmaceutical companies, state and federal health ministries.
Programme Implementation
Establishing an evidence base: This could be done by randomised controlled trial of vaccinating infants at the onset of labour, and another booster shot before the current regimen at 2 months to assess clinical outcomes. A randomised trial could also be done for adults over 20 years in limited geographical areas to assess efficacy, human resources and costs. A trial of up-skilling healthcare workers to be competent for routine pertussis screening in hospitals may be implemented and tried. Additionally, production of pamphlets and utilising media to promote health awareness of pertussis could be trialled to assess coverage, efficacy, cost and human resources.
Health promotion actions: Traditionally, health promotion activities have focused on public information, education or communication as the main method for improving knowledge and changing behaviours and thus, this should be emphasised in a pertussis preventative strategy. Dissemination of information through mass media by advertising, radio, posters and pamphlets around healthcare centres could be implemented in a cost effective way.
Organisations could also work together with pharmaceutical companies supplying vaccination. Furthermore, identified cases of pertussis should be reported early to a public health authority by private and public hospitals. Finally, prior to registration of doctors with the medical board, they could be required to undergo pertussis training.
Monitoring and recording of programme implementation and quality control
Increased attention must be given to the development of performance indicators which can be used to assist in assessing good management of people and resources, and assessment of success or failure. [19]
Cost-benefit analysis may be assessed for each class of preventative strategy, the availability of staff for an increasingly elderly population, assessment of penetration and impact of mass media and pamphlets for patient education could be accounted by production of surveys, and public notification s, mortality and morbidity data may constantly be monitored to assess efficacy of increased DTPa.
Program evaluation
Health literacy may be evaluated using measures such as assessing pertussis-related knowledge, attitudes, motivation, behavioural intentions, personal skills and self efficacy of the public. [19]
Outcomes regarding internal governmental policy developmental process, and lobbying leading to legislative change could be reviewed using measures such as policy statements, resource allocation and organisational practices. Finally, data of social outcomes (such as quality of life, equity) and health outcomes (national data on reduced morbidity, disability, avoidable mortality) may be evaluated to assess whether the preventative strategy was successful, or, if there are any program failures, may be traced to re-examine potential solutions.
Despite the largely successful history of immunisation in dramatically decreasing the incidence of pertussis, especially in terms of the number of hospitalisations and deaths, a number of changes to the immunisation strategy may be overdue. Control of the disease still remains a challenge in 21st century Australia, with increased notification rates documented in those under the age of 6 months and over the age of 20. GPs, often the fi rst point of contact, should familiarise themselves with the epidemiology those at greatest risk of pertussis, and off er vaccination accordingly. Moreover, individuals, health professionals, health organisations and governments must work synergistically to develop novel preventative strategies against modifi able risk factors, such as by increasing the number of booster vaccines, increasing surveillance, and greater dissemination of information to the population, to minimise burden of the disease for a sustainable future.
I would like to acknowledge Prof. Gabrielle Bammer, Director, National Centre for Epidemiology and Population Health and A/Prof. David Harley, Associate Dean of Population Health Teaching and Learning for awarding the ANU Medical School Population Health Prize towards this article.
Conflicts of interest
None Declared.
J Choi:
[1] Australia. Pertussis Vaccines for Australians: Information for Immunization Providers. National Centre for Immunisation Research and Surveillance fact sheet. November; 2009.
[2] Australia. Vaccine Preventable Diseases and Vaccination Coverage in Australia 2003-2005. Australian Government Department of Health and Ageing. November; 2007.
[3] Wood N, McIntyre P. Pertussis: Review of epidemiology, diagnosis, management and prevention. Paediatr Respir Rev. 2008;9:201-12.
[4] Quinn H, McIntyre. Pertussis epidemiology in Australia over the decade 1995-2005: Trends by region and age group. Commun Dis Intell. 2007;31:205-15.
[5] Paterson J, Sheppeard V. Nosocomial pertussis infection of infants: Still a risk in 2009. Commun Dis Intell. 2010;34:440-3.
[6] Senanayake S. Pertussis in Australia today: A disease of adolescents and adults that can kill infants. Aust Fam Physician. 2007;36:51-5.
[7] Australian Institute of Health and Welfare Interactive National Hospital Data [Internet]. 2010 [Cited 2011 May 14] Available from:
[8] Cherry J. The epidemiology of pertussis: A comparison of the epidemiology of the disease pertussis with the epidemiology of Bordetella pertussis infection. Paediatrics. 2003;115:1422-7.
[9] Weekly epidemiological record: Pertussis Vaccines WHO position paper, 2010. World Health Organization. 2010;85:385-400.
[10] Long, S. Age Specifi c Presentation and Burden of Pertussis. Adv Stud Med. 2005;5:S444-9.
[11] Yeh S, Mink C, Edwards M, Torchia M. Clinical Features and Diagnosis of Bordetella pertussis infection in infants and children. Waltham, MA, USA: Up to Date; 2010.
[12] Wright S and Tenn N. Pertussis Infection in Adults. South Med J. 1998;91:702-9.
[13] Biellik R, Patriarca P, Mullen J, Rovira E, Brink E, Mitchell P, et al. Risk factors for community and household acquired Pertussis during a large scale outbreak in central Wisconsin. J Infect Dis. 1988;157:1134-40.
[14] Kolos V, Menzies R, McIntyre P. Higher pertussis hospitalization rates in indigenous Australian infants, and delayed vaccination. Vaccine. 2006;25(4):588-90.
[15] Webb P, Bain C and Pirozzo S (2005) Essential Epidemiology. New York, USA:Cambridge University Press; 2005.
[16] Yeh S, Edwards M, Torchia M. Treatment and prevention of Bordetella pertussis infection in infants and children. Waltham, MA, USA: Up to Date; 2010.
[17] Forsyth K, Konig C, Tan T, Caro J, Plotkin S. Prevention of pertussis: Recommendations derived from the second Global Pertussis Initiative roundtable meeting. Vaccine. 2007;25:2634-42.
[18] Mills S. Now wash your Steth. Medical Student Journal of Australia. 2011;2:42-3.
[19] Pencheon D, Guest C, Melzer D, Gray J. Oxford Handbook of Public Health. Oxford, United Kingdom: Oxford University Press; 2001.

Review Articles Articles

The influence of vitamin D on cardiovascular disease

Background: Vitamin D is essential for many biological functions in the body. Populations that are deficient in vitamin D have increased cardiovascular morbidity and mortality. Current research is controversial, and the evidence base is still developing. This review looks at the interaction between vitamin D levels and cardiovascular disease, including the major cardiovascular risk factors – diabetes, obesity, hyperlipidaemia and hypertension. Methods: A literature review was undertaken through MEDLINE / PubMED / Ovid / Springerlink / Web of Science databases. The terms, “vitamin D”, “vitamin D deficiency”, “cardiovascular risk”, “cardiovascular disease”, “structure”, “function”, “ergocalciferol”, “cholecalciferol”, “calcitriol”, “vitamin D receptors”, “1α-hydroxylase”, “diabetes”, “obesity”, “hypercholesterolaemia”, “hyperlipidaemia” and “hypertension” were used. Sixty-eight articles were selected and analysed, with preference given to studies published in English and published within recent years. Results: There is a correlation between adequate vitamin D levels and type two diabetes mellitus, but limited research to support this. Obesity, physical inactivity and elevated circulating lipids are more common in vitamin D deficiency. These relationships have not been shown to be causal. Some studies have shown an inverse correlation between hypertension and vitamin D levels, while others have shown no relationship. Conclusion: The studies analysed show there is limited evidence to suggest that cardiovascular disease may be prevented by adequate vitamin D levels. There are few well-designed studies that demonstrate the relationship between the cardiovascular risk factors – diabetes, obesity, hyperlipidaemia, hypertension, and vitamin D. Further research is needed to clarify the infl uence of vitamin D on cardiovascular disease.

What is vitamin D, and how do you get it?

Vitamin D is a group of secosteroids, derived from steroid precursors by the opening of the steroid B-ring between carbons nine and ten. Vitamin D has a cis-triene structure which is susceptible to oxidation, ultraviolet (UV) light-induced conformational changes, heat-induced conformational changes and attack by free radicals. [1,2]

Cholecalciferol, also known as vitamin D3, is a 27-carbon molecule derived from cholesterol. [2] It is available through diet and through synthesis in the skin. [1] 7-dehydrocholesterol found in skin is converted to previtamin D3 following exposure to ultraviolet B (UVB) light. Previtamin D3 is unstable and breaks down to vitamin D3. This binds to vitamin D binding protein (VDP) and is delivered to the liver and other sites of action via the circulatory system. [3,4] Vitamin D levels are regulated in the body in a number of ways. While exposure to UVB radiation causes vitamin D3 production in the skin, excessive exposure to sunlight degrades it into inactive photoproducts. [5]

Ergocalciferol, also known as vitamin D2, is a 28-carbon molecule produced by irradiation of ergosterol found in plant and fungi, which is available through diet. [2,4] Vitamin D2 and D3 (available via diet) are absorbed with fat in the gastrointestinal system into chylomicrons, which are delivered to the liver or storage sites outside the liver, such as adipose tissue. [1]

The liver converts vitamin D3 to biologically inactive 25-hydroxyvitamin D3 (calcidiol). This is converted to biologically active 1,25-dihydroxyvitamin D3 (calcitriol) under the infl uence of renal 1α-hydroxylase predominantly in the kidney. [5,6] 1α-hydroxylase is under the control of parathyroid hormone (PTH). Calcitriol is regulated by negative feedback on itself, by increasing production of 25-hydroxyvitamin D-24 hydroxylase. This enzyme catabolises calcitriol to its biologically inactive form, calcitroic acid, which is excreted in the bile and urine. Other factors such as serum phosphorus, calcium and fibroblast growth factor 23 (FGF-23) can increase or decrease production of calcitriol. Increased serum calcium levels reduce PTH, causing down-regulation of 1α-hydroxylase, reducing calcitriol, and therefore calcium levels. [5,6] A simplified diagram of the biological function of vitamin D is outlined in Figure 1.

1α-hydroxylase is the rate-limiting step in production of calcitriol. Although calcidiol is the most abundant form of vitamin D in the blood, it has minimal capacity to bind to vitamin D receptors (VDRs). 1α hydroxylation of calcidiol to calcitriol causes vitamin D to gain affinity for VDRs. [7] In recent years, 1α-hydroxylase has been found to exist at many extra-renal sites. The role of extra-renal vitamin D activation remains controversial, but may play a role in the hypothesised actions of vitamin D. [8]

VDRs are found in almost every cell in the body. Calcitriol actions occur through intracellular receptors and interaction with DNA via the classic steroid pathway. These receptors were originally thought to regulate genes responsible for regulation of serum calcium and phosphate. [1] More recently, they have been found to regulate transcription in many tissues and cells, including immune cells, bone marrow, skin, muscle and intestine. [1,9]

How does vitamin D affect cardiovascular disease?

Vitamin D deficiency has been associated with high blood pressure, risk for cardiovascular-related deaths, symptoms of depression, cognitive deficits and mortality. [10] Calcitriol inhibits renin synthesis, increases insulin production and increases myocardial contractility. [11-13] Vitamin D deficiency reduces serum calcium levels, causing an increase in PTH, which promotes atherosclerosis and cardiovascular risk. [14,15]

The majority of evidence for the role of vitamin D in cardiovascular disease (CVD) has arisen from studies involving patients with end stage renal disease. Cardiovascular mortality is ten to twenty times higher in patients undergoing dialysis. [16] In patients using dialysis, the risk of death from CVD can be reduced with vitamin D replacement. [17,18]

As kidney function deteriorates, calcitriol levels decline. [19] Reduced calcitriol production can lead to hypocalcemia, and in turn, compensatory elevated PTH. Overstimulation of the parathyroid gland eventually leads to secondary hyperparathyroidism (SHPT). [20] Patients with ESRD are thought to suffer from reduced cardiac inotropy, increased heart weight, increased myocardial collagen content, and increased vascular smooth muscle cell proliferation as a result of the vitamin D depletion. PTH excess may impair intracellular calcium metabolism of the cardiomyocyte and promotes chronic atherosclerosis. Elevated PTH may increase cardiac contractility, insulin resistance, calcium and phosphate deposition in vessel walls, chronic myocardial calcification, and chronic heart valve calcification. [14,15] In patients with SHPT, treatment advice usually consists of correction of calcitriol deficiency using calcitriol or vitamin D analogues. [6]

Mechanisms for cardiovascular risk reduction with vitamin D supplementation include the inhibition of smooth muscle proliferation, the suppression of vascular calcification, the down-regulation of inflammatory cytokines, the up-regulation of anti-inflammatory cytokines, and the negative regulation of the renin-angiotensin-aldosterone system (RAAS). [21-26] Inappropriate stimulation of the RAAS is associated with hypertension, myocardial infarction and stroke. [14] Calcitriol treatment has been shown to reduce blood pressure, renin activity and angiotensin II levels. [27] The effects of vitamin D deficiency on the cardiovascular system are outlined in Figure 2.

A systematic review and meta-analysis looked at the relationship between the naturally occurring level of vitamin D and cardiometabolic disorders including CVD, diabetes and metabolic syndrome. [28] Twenty-eight studies were selected, including nineteen crosssectional studies, three case-control studies and six cohort studies, analysing 99,745 patients. [28] High vitamin D levels were associated with a 43% reduction in cardiometabolic disorders. [28] There was a significant association between high levels of vitamin D and risk of having cardiovascular disease (33% reduction), type two diabetes (55% reduction) and metabolic syndrome (51% reduction). [28] Vitamin D supplementation has been shown to have a protective effect in limited studies of CVD, but further research is needed. [29]


The research surrounding the interaction between vitamin D supplementation and type two diabetes mellitus is controversial. To date, there have been no adequate, large and prospective, randomised controlled trials to test the efficacy of vitamin D supplementation for the prevention and treatment of type two diabetes mellitus. The current available data allows a recommendation that further research be conducted to determine whether adequate vitamin D levels may prevent the onset of type two diabetes. Type one diabetes mellitus will not be discussed in this review.

Insulin resistance has been associated with low serum vitamin D, which improved after treatment with vitamin D. [30-36] One study demonstrated a positive relationship between calcitriol and insulin sensitivity, and a negative effect of vitamin D deficiency on beta cell function. [12] These studies are limited by small sample size, subject selection and lack of randomisation. However, there was a clinical correlation and it is worthwhile investigating further the possibility of improvement in insulin sensitivity with vitamin D supplementation. Serum blood sugar levels and prevalence of type two diabetes mellitus increases with age, and vitamin D levels tend to fall with age. [37,38] Type two diabetes is associated with systemic inflammation, which may induce beta-cell dysfunction and death. [39] Several studies show that vitamin D could directly affect beta-cell growth and differentiation via modulation of systemic inflammation and the immune response. [39-42] One of these was a double-blinded 39-week follow-up study of interleukin-1 blockade with anakinra. [40] Although being limited by small sample size and limitations in subject selection, the study showed improvement in markers of systemic inflammation 39 weeks after treatment withdrawal. [40]

Several studies indicate that calcitriol regulates beta-cell function by regulating intracellular calcium levels. This is thought to influence insulin secretion, increase beta-cell resistance to apoptosis and increase beta-cell replication. Calcitriol is thought to bind to nuclear VDRs in the beta-cell to increase preproinsulin mRNA level. Research to support this hypothesis is limited, due to being conducted in rats. [39,43-45]

Obesity and hyperlipidaemia

Studies have shown that high body mass index (BMI) is associated with low serum vitamin D levels. [46] Vitamin D is fat soluble and readily stored in adipose tissue. [1,47] Sequestration of cholecalciferol in adipose tissue reduces bioavailability in obese individuals. [1,48,49] The distribution of fat may be associated with vitamin D status, but this relationship may be dependent on metabolic factors. [49]

Vigorous physical activity is a strong and modifiable contributor to vitamin D status. This may be due to sun exposure correlated with physical activity, however, a number of studies have shown the positive effect on vitamin D status may be independent of sun exposure. [50-54] Further research is needed to clarify this.

A large, prospective study of the modifiable predictors of vitamin D status was conducted using 2,621 healthy individuals aged 55-74 in the USA. [46] Predictors of low vitamin D status were found to be low dietary vitamin D intake, BMI > 30kg/m2, physical inactivity and low milk and calcium supplement intake. [46] There is an inverse relationship between apolipoprotein A-I and high density lipoprotein cholesterol with vitamin D levels in a survey of 358 Belgian people. [55] This relationship was not shown to be causal, but further research is warranted to see if vitamin D provides this cardioprotective link.

Vitamin D deficiency may increase insulin resistance and thereby increase circulating lipids, but supplementation has not been shown to improve circulating lipid levels. [56,57] Statin therapy increases the circulating levels of 7-dehydrocholesterol, leading to an increase in conversion to vitamin D (in the presence of UVB radiation), and therefore vitamin D levels. [58-61]


To date, there are few good quality randomised controlled trials looking at the relationship between vitamin D levels and blood pressure. There is weak evidence to suggest that there may be a relationship between the two, however, further research is needed to draw any conclusions that may change the management of blood pressure.

Vitamin D may regulate blood pressure via an interaction with the RAAS, which is often activated in hypertension. Calcitriol is a known negative regulator of the RAAS. [11,21] The effects of vitamin D on the suppression of renin activity may be due to increased intracellular calcium levels. [62] It is hypothesised that vitamin D regulation of renin is independent of calcium metabolism, by regulating renin mRNA production with VDRs. [11] This study was completed using a line of cells derived from transgenic mice kidney tumours. [11]

There are some studies which show an inverse correlation between vitamin D levels and blood pressure. [63-66] A meta-analysis which included eleven randomised controlled trials (small, variable methodological quality) found weak evidence to support a small effect of vitamin D on blood pressure in studies of hypertensive patients. [67] There was a small statistically significant reduction in diastolic blood pressure, and no significant reduction in systolic blood pressure in hypertensive subjects supplemented with vitamin D or UV radiation. [67]

Several studies have shown differing results when trying to establish a relationship between vitamin D intake and hypertension. [10] There are two cross-sectional studies that have been completed using the Third National Health and Nutrition Examination Survey data. One study demonstrated a significant difference in systolic blood pressure and pulse pressure between the highest and lowest quintile groups divided by vitamin D level. [10,63] Participants with hypertension were excluded from analysis. [63] Another study revealed increased systolic blood pressure with reducing levels of vitamin D, and a twenty percent reduction in systolic blood pressure in those with vitamin D levels greater than 80 nmol/L compared with those with less than 50 nmol/L. [64] Both of these studies had a good sample size, but were limited by the methods of the study. [10] A cross-sectional study using a different data set with low prevalence of vitamin D deficiency showed no association between systolic blood pressure and vitamin D level. [10,65] A different study did not show any significant relationship between vitamin D levels and blood pressure after adjusting for confounding variables, however, this may have been due to low estimated vitamin D intake. [10,68]


Vitamin D is an important molecule to consider in the pathogenesis of cardiovascular disease. Current research shows that vitamin D deficiency contributes to cardiovascular morbidity and mortality. The mechanisms proposed for this include direct actions on the heart and vasculature, as well as by increasing the risk of cardiovascular risk factors such as diabetes, obesity, hyperlipidaemia and hypertension. Further research is needed to clarify the influence of vitamin D on cardiovascular disease and its risk factors, and whether vitamin D is an efficient, cost-effective and safe intervention to prevent cardiovascular morbidity and mortality.


Dr Ruan Lakemond, for his kind assistance in proof-reading this article and technical support. Prof Rick Jackson, for his generous support and help finding a suitable topic.

Confl icts of interest

None declared.


R Lakemond: