Categories
Articles Editorials

The Australian Medical Student Journal: a nationwide endeavour

Welcome to Volume 4, Issue 1 of the Australian Medical Student Journal.

This issue of the AMSJ continues to develop our core aims of supporting medical student research by providing a dedicated journal for publication of outstanding medical student work and a focus on issues relevant to Australia in general and Australian medical students in particular. Key milestones for the Australian Medical Student Journal over the past months have included the online publication of the Australian Students’ Surgical Conference, the expansion of our editorial team to include seven new members, each talented upcoming physician-scientists, and a broader expansion of our medical student staff. Senior AMSJ staff are now located in every state across Australian and there are representatives at each medical school.

This issue the AMSJ received an unprecedented number of outstanding submissions from medical students across the country. Some key highlights for this issue include a timely review by Boulat and Hatwal of the case for male HPV vaccination. This review, published as the Australian government announces its world first initiative of immunising young men against HPV, was identified by our editorial team and reviewers as a excellent review of an important contemporary public health issue and has been awarded the best article prize for Volume 4, Issue 1. Other notable submissions include a rigorous comparative review of anaesthetic methods for paediatric elective inguinal herniotomy, a synopsis of treatment options for preventing cardiac sequelae in Kawasaki disease, a reflective essay on the humanising influence of fiction in psychiatry, and a case report of spontaneous intracranial hypotension. Editorials by Saion Chatterjee and Janindu Goonawardena discuss structural changes occurring in academic publishing and the current challenges faced by the medical workforce across Australia. We are also privileged to host articles from prominent Australians: Professor Larkins, Chair of European Molecular Biology Laboratory-Australia (EMBL-Australia) and the Victorian Comprehensive Cancer Centre (VCCC), Professor Bolitho, President of the Royal Australia College of Physicians (RACP) and Professor Hollands, President of the Royal Australia College of Surgeons (RACS), to provide a top-down perspective on issues important to medical students.

Health and medical research in Australia faces key challenges including sustainability and international competitiveness. The recent McKeon Review of Health and Medical Research in Australia provides a framework for how Australian researchers can help to maximise the health of all Australians and contribute on a global scale. A major facet of this review is the emphasis on collaboration. In a country with a population less than one fiftieth of our neighbours, China and India, and public research expenditure less than one thirtieth of the United States, collaboration is an integral component to achieving global impact. In his guest article, Professor Larkins, Chair of EMBL-Australia and the VCCC, offers his advice and experience as the Chair of two leading collaborative research initiatives in Australia. With the upcoming federal budget and election, we also spotlight the issue of sustainability in the healthcare system. Professor Bolitho of the RACP provides a considered perspective on the measures required to accommodate increasing numbers of medical graduates. Professor Hollands of the RACS and Associate Editor Janindu Goonawardena provide complementary perspectives on contemporary surgical training in Australia and discuss potential measures to address rural medical workforce shortages.

This issue of AMSJ represents the accumulation of many hours of voluntary work from AMSJ staff and reviewers. We have been privileged to lead a team of highly motivated, intelligent and hardworking medical students from across the country, without whom publication of this journal would not be possible. We would additionally like to thank our external peer reviewers, many who completed their first review this issue and many more who regularly contribute their time and expertise to the AMSJ. The initiative of publicly thanking reviewers will be continued this year, and their names published in the latter half of the year. Finally, we would like to thank all authors who contributed to the AMSJ and all our readers, who provide content and meaning to this publication. We hope you enjoy this issue and that it serves as motivation for medical students and nascent authors of future publications.

Categories
Articles Editorials

Freedom of information

Early last year, a David and Goliath battleraged between the most unlikely of foes. The gripes of a single blog post inspired a group of disaffected mathematicians and scientists to join forces and boycott the world’s largest publisher of scientific journals, Elsevier. Their movement, dubbed “Academic Spring”, was in response to the company’s political backing of the Research Works Act, a proposed bill in the United States (US) aimed at denying public access to scientific research funded by the US National Institute of Health (NIH). Drafted solely to benefit the interests of publishing companies, Elsevier reneged on its support for the bill following months of escalating protests and scathing publicity. Though the bill never saw the light of day, the struggle that unfolded was symptomatic of a more deep-seated and pervasive conflict between academics and publishers; a conflict that has been thrown into sharp relief by the rise of online publishing.

Since the publication of the first scholarly journal in 1665, journals have played an integral role in the scientific process. [1] As vanguards of modern day science, journals have been an enduring and authoritative source of the latest scientific research and developments. Academics form a key ingredient in the turnover and success of journals. Not only are they responsible for generating content, but they also volunteer as peer-reviewers for submissions relevant to their field of expertise and as mediators of the editorial process; a peculiar arrangement that plays into the hands of publishers. Before the arrival of the internet, journals facilitated the quick and widespread exchange of information throughout the scientific world. Publishers performed services including proofing, formatting, copyediting, printing, and worldwide distribution. [1] The digital age, however, rendered many of these tasks redundant and allowed publishers to dramatically reduce their costs. [1] Publishers also used the opportunity to offload further responsibilities onto the shoulders of academics, such as formatting and most copyediting, in order to significantly increase profits despite playing a limited role in the journal’s overall production.

The changing landscape of scientific publishing has seen commercial publishing firms acquire a lion’s share of the market from not-for-profit scientific societies in the last few decades. [2] The resulting monopolistic stranglehold has led to exorbitant subscription fees for access to their treasury of knowledge. Profit margins have hovered between 30-40 percent for over a decade, due in part to subscription prices outpacing inflation by seven percent per annum. [3] Moreover, publishers have exploited the practice of offering journals subscriptions in bundles, rather than on an individual needs basis, a crucial ploy underlying their profits. [4] Long-standing price increases, accompanied by dwindling library budgets, have gravely hampered the ability of libraries, universities, and investigators to acquire the most up-todate publications necessary for research and education. [4] The total expenditure on serials by Australian university libraries in 2010 was a staggering AU$180 million. [5] Even the most affluent libraries, such as Harvard, are declaring the situation as untenable and are resorting to subscriptions cuts. [3]

Along with cost, the principle of access for clinicians, scientists, and the general public alike underscores the ensuing debate. There is little argument that the accessibility of scientific findings is critical to the advancement of scientific progress. Consequently, the great paywalls of publishing houses have fostered an environment that stagnates the translation of science to the bedside and stifles medical innovation. Peer-reviewed literature is often funded by taxpayer-supported government grants. In Australia and New Zealand, over 80% of research and development is funded by the public purse. [6] In effect, governments have been held ransom by firms privatizing the profits accruing to publicly-financed knowledge. The barriers of access and cost also extend to developing nations. Without access to reliable medical literature, efforts to develop sustainable health care systems in these regions are severely undermined.

Researchers are equally culpable for their current plight. Typically, works of intellectual property warrant financial remuneration. However, writing for impact instead of payment has become both intrinsic and unique to academic journals, a paradigm from centuries before when journals were unable to pay authors for their work. [3] Impact, a proxy measure developed by commercial publishers, reflects an academic journal’s visibility for a given year. It is derived from the ratio between the average number of citations per article received during the two preceding years and the total number of articles it published during the same period. [7] The higher the impact factor of a journal, the greater its clout and influence. The importance placed on impact factor has become ingrained in the collective psyche of academia. Academics are competitively assessed on their publication record in scientific journals to secure grants and advance their careers. Inevitably, researchers have become servile to an archaic system, which serves only the interests of commercial publishers.

Open access (OA) represents a new business model in the academic journal industry, underpinned by the growth and reach of the internet. It provides unfettered online access to all research material, as well as the right to copy and redistribute it without restrictions. [1] Open access (OA) uses two channels of distribution: the “gold” or the “green” paths. [1] The “gold” path publishes articles in freely available OA journals that maintain peer review to preserve their academic reputations. The Public Library of Science (PLoS) and BioMed Central (BMC) are leading examples of OA publishers. The “green” path requires authors to self-archive their work on an online repository, available free of charge to the public. [1] Table 1 highlights some of the differences between traditional and OA journals.

Open access (OA) offers many advantages compared to traditional journal publishing. Evidence shows that OA has substantially increased the amount of scholarly work available to all, regardless of economic status or institutional affiliation, increasing the probability of research being read and, accordingly, of being cited. [8] Open access (OA) can integrate new technological approaches such as text mining, collaborative filtering, and semantic indexing, and has the potential to encourage new research methodologies. [8] A significant bone of contention with traditional journals has been the need for authors to relinquish copyright of their material. Open access (OA) allows authors to retain copyright, and provides readers and other authors with the rights to re-use, re-publish, and, in some cases, create derivatives of their work. [8] Furthermore, OA bridges both the digital and physical divide between the developing and developed worlds, mitigating some of the limitations faced by scientists in low-income countries to publish their work. Institutional repositories and OA publication fee waivers have been instrumental in promoting their research profile onto the international stage, by shedding the burden of cost. [9]

Despite offering free access to readers, OA has been plagued by its share of criticism. Traditional publishing firms, one of its fiercest opponents, contend that OA journals shift the cost of production from consumer to author, with fees ranging from $1,000-5,000 per article. [3] Whilst levelling this critique, commercial firms overlook the fact that they also foist publication fees onto authors which may even exceed the costs of OA journals. [1,3] Publication costs are now a common element in grant fund applications, and authors incur minimal to no charge. Inevitably, ethical concerns also arise from the OA model. The author-pay model may compromise the peerreview process as journals become financially dependent on researchers to publish articles. However, these concerns have been assuaged in recent years, due to the widespread number of high-quality OA journals that employ robust peer-review on par with their subscription counterparts. [1] The “green” route also poses problems for authors who may not possess the technical capabilities or resources to self-archive articles.
Open access (OA) represents the fastest growing business model for academic journals, and is likely to remain sustainable in the long-term. Many OA journals are now highly trusted, referenced, indexed, and well received. Its support has been bolstered by the evolving mandates of research funding agencies, including Australia’s National Health and Medical Research Council (NHMRC), the United Kingdom’s Wellcome Trust, and the NIH, placing research funded by their grants into the public domain within a year of initial publication. [7,10] Major data aggregators are also facilitating this trend, including PubMed and OVID, releasing OA databases and platforms dedicated to OA material. [11] Estimates project that 60 percent of all journal content will be published in OA journals by 2019. [11] Moreover, OA journals are rapidly approaching the same scientific impact and quality as subscription journals, particularly in the field of biomedicine, as suggested by one study. [7] Many have opined that OA could redefine measures of impact, using additional metrics such as number of downloads, bookmarks, tweets, and Facebook likes.Proponents of OA have turned their attention to how corporations like drug and chemical companies can support its efforts, which benefit from free access while contributing only a small subset of scientific articles and fees overall.

The advent of the internet has created a realm of possibilities for some and a minefield of challenges for others. Journals have navigated such obstacles for centuries, embracing new opportunities and adapting to change. Although the internet has effectively transformed publishers into “de facto” gatekeepers of their lucrative commodity, it has also been the impetus behind the OA revolution, proving to be a more cost-effective and equitable alternative to traditional publishing. But while OA continues to develop into the mainstay of journal publishing, perhaps its most immediate impact will be to diversify competition and precipitate a cultural change within the industry that sees science re-emerge at the forefront of its interests.

Conflict of interest
None declared.

Correspondence
S Chatterjee: s.chatterjee@amsj.org

References

[1] Albert KM. Open access: Implications for scholarly publishing and medical libraries. J Med Libr Assoc. 2006 Jul;94(3):253-62.

[2] Jha A. Academic spring: How an angry maths blog sparked a scientific revolution. The Guardian. 2012 Apr 9.

[3] Owens S. Is the academic publishing industry on the verge of disruption. U.S. News and World Report. 2012 Jul 23.

[4] Taylor MP. Opinion: Academic publishing is broken. The Scientist. 2012 Mar 19.

[5] Australian higher education statistics [Internet]. Council of Australian University Librarians; 2009 [updated 2012 Nov 29; cited 2013 Mar 5]. Available from: http://www.caul.edu.au/caul-programs/caul-statistics/auststats.

[6] Soos P. The great publishing swindle: The high price of academic knowledge. The Conversation. 2012 May 3.

[7] Björk BC, Solomon D. Open access versus subscription journals: A comparison of scientific impact. BMC Med. 2012;10(73).

[8] Wilbanks J. Another reason for opening access to research. BMJ. 2006;333(1306).

[9] Chan L, Aruachalam A, Kirsop B. Open access: A giant leap towards bridging health inequities. Bull. World Health Organ. 2009;87:631-635.

[10] Dissemination of research findings [Internet]. National Health and Medical Research Council; 2012 Feb 12 [updates 2013 Jan 25; cited 2013 Mar 4]. Available from: http://www.nhmrc.gov.au/grants/policy/disseminationresearch-findings

[11] Rohrich RJ, Sullivan D. Trends in medical publishing: Where the publishing industry is going. Plast Reconstr Surg. 2012;131(1):179-81.

Categories
Articles Editorials

Thought the ‘bed shortage’ was bad, until the ‘surgeon shortage’ came along

“Make up your mind how many doctors a community needs to keep it well. Do not register more or less than this number.’’ George Bernard Shaw

If you have ever had the opportunity of finding yourself in a surgical theatre, the last thing you want to have on your mind are doubts about the person holding the scalpel. To ensure the highest professional standards are maintained, trainees of the Royal Australasian College of Surgeons (RACS) undergo a rigorous five to six year postgraduate training program prior to final qualification as a surgical consultant. [1] However, such a long and demanding training program has proven to be a double-edged sword for the surgical speciality. Studies have shown that one in four surgeons plan to retire in the next five years and that only sixteen percent of surgeons were under 40 years old. [2] The same study demonstrated that the average retirement age for surgeons has decreased by ten years. [2] These factors place an immense amount of pressure on surgical training programs, particularly in an era where the ageing population is creating more demand for surgical services. [2] While workforce shortage issues are by no means unique to the RACS, and indeed are felt by many medical colleges across Australia, this editorial will focus on the RACS to illustrate the issues affecting a broad range of medical specialities.

Along with many medical colleges around Australia, the RACS faces a looming workforce crisis with an ageing workforce approaching retirement and an ageing population with increasing healthcare needs, combining to create a critical demand for scarce services. The 2011 annual report published by the RACS highlighted that the number of first year surgical trainees across all specialties was 246 [3] compared to the 3000+ medical students graduating from around the country each year. While this represents a relatively small fraction of the available workforce pool, the RACS has taken the initiative to increase the number of surgical trainee positions by twelve percent compared to 2010. [3] Despite these gains, the RACS estimates that at least another 80 surgeons will have to graduate each year in addition to the 184 new surgeons currently graduating each year, in order to begin to redress surgeon workforce shortage. [4,5]

Low trainee numbers represent a composite of many factors, including financial limitations, need for skilled supervision and opportunity for practical experience. [6] The public sector has reached its full capacity for surgical training posts as such posts are funded by the State governments hence they are limited by budget provisions. [5] Consequently, underfunding, chronic shortage of nursing staff and lack of resources in public hospitals are seen as some of the main reasons for extended waiting times for surgery. [7] Due to the lack of such resources, it is a common trend now to see surgical lists being limited or procedures being cancelled because of time constraints. [7] Increasing the number of trainee posts will require significant fundamental changes, namely greater resourcing of the public health system. [6] To avoid the looming workforce crisis, governments will have to move quickly to ensure adequate training posts are in place across all medical specialties. [3,5] In Australia, more than 60% of elective surgery is in the private sector. [5] Novel training opportunities, such as those offered by the private sector, should also be considered as clinicians with the appropriate range and depth of experience required to train junior doctors are not limited to the public sector. [5] Lack of resources, funding, safe working hours and reduced clinical exposure are all elements that add to this crisis of looming workforce shortage. [6,8]

While there is a compelling argument to expand the number of trainee positions around Australia, the challenge is to maintain the highest standards for surgical trainees. [7] Emphasis on the number of training positions created is the priority of any college and is a crucial aspect in offering quality treatment in both the public and private hospitals. [7] However, increasing the number of trainees to accommodate and cope with surgeon shortage might result in reduced individual theatre time, which is not acceptable. [4,7] While this may relieve the workforce shortage, however, it would only create more specialists with limited exposure to a wide range of surgical presentations. [7] The aim of surgical training is to ensure that trainees progress through an integrated program that provides them with the highest professional responsibility under appropriate supervision. [9] This not only ensures exceptional quality but also enables trainees to acquire the competencies needed to perform independently as qualified surgeons. There are concerns nonetheless that if there is a large intake of surgeon trainees it may favour ‘quantity’ of trained surgeons over ‘quality’. [7] This is unacceptable, not only for the safety of our patients, but also in a world of increasing medico-legal implications and litigation. [7]

Another challenge affecting the surgical profession and surgical trainees is the issue of safe working hours. Currently, the reported working hours of the surgical workforce on average is 60 hours per week, excluding 25 hours per week on average spent on-call. [5] Although safe working hours are less of an issue in Australia than the rest of the world, it still affects surgical training. [10] Safety and wellbeing of surgical trainees is a top priority of the RACS. [7] Reduced trainee hours have been encouraged by research showing that doctor fatigue compromises patient care, as well as awareness that fatigue hampers learning. [10] Long hours traditionally worked by surgeons may result in concerns regarding safe working hours and the possibility that the next generation of surgeons will seek enhanced work-life balance. [4,7] Adding to the ominous shortage of surgeons, the challenge still remains whether surgical trainees can still assimilate the necessary clinical experience in this reduced timeframe. [7] More and more trainees place increased emphasis on work-life balance [5], making alternate specialisation pathways a real possibility that many consider.

Many, if not all, of the issues felt by the RACS across Australia are rarefied in rural Australia. Rural general surgery, much like its general practice counterpart, is facing an impending crisis of workforce numbers. [11] Despite increasing urbanisation, approximately 25% of Australians still live in rural Australia [12] and it is this portion of the population that is likely to be the first and worst affected by any further constriction in medical workforce numbers. Single or two-man surgical practices provide service to many rural and remote centres. [11] However in many areas where surgical services could be supported, no trainee surgeon is available. [11] Many current rural surgeons are also fast approaching retirement age. [11] In past years retention of surgeons in rural communities has been strong. [13] The lifestyle benefits, challenges and rewards all combined, have ensured that a large amount of rural surgeons are growing old in the country. [13] However, this perception may well be a thing of the past. [13] Younger surgeons are more likely to consider time off on call, annual leave and privacy as lifestyle considerations which compel them back towards the metropolitan area. [13] Such a shift in attitude towards limiting one’s workload combined with the continuing decline in Australian rural practices will apply various additional pressures on the rural surgeon workforce in the near future. [11]

Two main factors that determine if a trainee surgeon is more likely to pursue a rural career are the exposure to good quality rural terms as an undergraduate and having a rural background. [11,13] Selections for rural posts are more common in doctors from a country background who are more likely to return to, and remain in, a rural practice. [12,13] Acknowledging this factor, many Australian medical schools have now incorporated both mandatory and voluntary rural terms as a part of their curriculum. [11] In addition to these undergraduate initiatives, ongoing rural placements during postgraduate years may need to be established and given greater prominence. [11] A trainee being allocated to the same rural location over a period of years increases the possibility of the trainee settling in the same rural location following their training. [13] This may be due to familiarity with the social and cultural setting as well as the desire to provide continuous care for his/her patients. [13] As a result of these undergraduate and/or postgraduate initiatives, we can expect to witness the next generation of advanced surgical trainees with a foundation of rural experience, demonstrating a willingness to undertake rural terms as an accepted and expected component of their general surgery training. [11,13] These trainees may then choose to settle in the same rural location following training, thus decreasing the rural surgeon shortage.

The aim of surgical training is to ensure that trainees progress through an integrated program that provides them with increasing professional responsibility under appropriate supervision. [8] This enables them to acquire the competencies needed to perform independently as qualified surgeons. [9] The RACS has taken major steps to address its workforce shortage. Continuing efforts to provide for trainees and their needs are given place of prominence in the RACS 2011-2015 strategic plan. The RACS’ role in monitoring, coordinating, planning and provisioning of services, as well as obtaining adequate funding for surgical training programs, remains a major responsibility of the College. Emphasis on rural rotations at an undergraduate and early postgraduate level, consideration of the work-life balance of both trainees and surgeons and sufficient staffing of theatres, will help eradicate the surgeon shortage whilst ensuring that the finest surgical education and care is available to Australians into the future.

Conflict of interest

None declared.

Correspondence

J Goonawardena: j.goonawardena@amsj.org

References

[1] The College of Physicians and Surgeons of Ontario. Tackling the Doctor Shortage. Ontario: CPSO; 2004. p. 5

[2] Surgeon shortage looms. The Hobart Mercury 2006 March 22:26

[3] The College of Surgeons of Australia and New Zealand. The Royal Australasian College of Surgeons Annual Report 2010. Melbourne: RACS; 2011. p. 9

[4] Royal Australasian College of Surgeons. (2011, October 7). Surgeons warn of looming workforce crisis [Media release]. Retrieved from http://www.surgeons.org/media/293538/MED_2011-10-07_Surgeons_warn_of_looming_workforce_crisis.pdf

[5] Royal Australasian College of Surgeons. RACS 2011: Surgical Workforce Projection to 2025 (for Australia). Melbourne: RACS; 2011. P. 8-57

[6] Amott DH, Hanney RM. The training of the next generation of surgeons in Australia. Ann R Coll Surg Engl 2006; 88:320–322.

[7] Berney CR. Maintaining adequate surgical training in a time of doctor shortages and working time restriction. ANZ J Surg. 2011; 81:495–499.

[8] Australian Medical Association Limited. (2005 April 5). States and territories must stop passing the buck on surgical training [Media Release]. Retrieved from http://ama.com.au/node/1966

[9] Hillis DJ. Managing the complexity of change in postgraduate surgical education and training. ANZ J Surg. 2009; 79: 208–213.

[10] O’Grady G, Loveday B, Harper S, Adams B, Civil ID, Peters M. Working hours and roster structures of surgical trainees in Australia and New Zealand. ANZ J Surg. 2010; 80: 890–895.

[11] Bruening MH, Anthony AA, Madern GJ. Surgical rotations in provincial South Australia: The trainees’ perspective.  ANZ  J Surg. 2003; 73: 65-68.

[12] Green A. Maintaining surgical standards beyond the city in Australia. ANZ  J Surg. 2003; 73: 232-233.

[13] Kiroff G. Training, retraining and retaining rural general surgeons. Aust. N.Z.J. Surg. 1999; 69:413-414.

 

Categories
Letters Articles

Pentraxin 3 – A new player in twinning frequency

The conception of dizygotic twins is a complex trait.

It is thought to be influenced by a variety of environmental and genetic factors and displays significant regional variation in prevalence worldwide. [1] For example, in Sub-Saharan areas of Africa, twinning is very common (~23 per 1000 pregnancies), while in Asia twinning is much rarer (~5-6 per 1000 pregnancies). [2] Recent research has sought to determine the reasons behind the increased frequency of twinning in regions of Sub-Saharan Africa. Independent studies of women from Gambia and Upper East Ghana have given insight into gene mutations which may possibly increase the fertility of women and hence the frequency of twinning. Specifically, it was found that certain single-nucleotide polymorphisms (SNPs) in the gene of pentraxin 3 (PTX3), a key player in human fertility and innate immunity, occurred in higher frequency amongst the mothers of twins. [3] This report will review the known functions of PTX3 in immunity and fertility and their relation to twinning frequency.

Pentraxin 3 in innate immunity

PTX3 is a soluble pattern recognition receptor, which belongs to the acute phase reactants superfamily. [4] In the innate immune response, PTX3 is produced in response to primary pro-inflammatory signals such as interleukin 6 (IL-6) release or toll-like receptor activation. [5] It participates in immunity by recognising pathogens, facilitating complement activation and opsonisation. [6] Indeed, it is involved in immune defence against Aspergillus, Pseudomonas, Salmonella, Mycobacterium tuberculosis, cytomegalovirus and influenza. [7-9] Known mechanisms of anti-pathogenic action include the binding of sialylated ligands on PTX3 to membrane proteins such as haemagglutinins found in influenza viruses and cytomegaloviruses. As haemagglutinins are used by viruses for fusion and entry to host cells, the binding of PTX3 ligands to the haemagglutinins can block this function and hence lower the chance of viral infection.  [7,8] The anti-viral actions of PTX3 against cytomegalovirus can also activate downstream immune components such as interferon regulatory factor 3 (IRF3) and the interleukin-12/interferon gamma (IL-12/IFN)-γ-dependent effector pathway, which in turn heighten anti-fungal defences against species such as Aspergillus. [8] Previous experiments performed by Garlanda et al. also show that PTX3-null mouse models were more susceptible to fungal infections, suggesting that PTX3 plays a non-redundant antifungal role. [10]

Pentraxin 3 in fertility

PTX3 is not only a major player in immunity, it has also been demonstrated to be linked to fertility in various studies. Specifically, PTX3 interacts with proteins such as TNF-stimulated gene 6 (TSG6) and inter-alpha-trypsin inhibitor (IαI) to form multimolecular constructs which facilitate cross-linking in the hyaluronan matrix that surrounds the cells of the cumulus oophorus. [11] This is crucial to the stability and organisation of the cumulus matrix, as shown in animal studies where PTX3-null mice produced ova with abnormal cumulus oophorus, which led to lower litter counts. [12,13] The infertility resulting from PTX3 knockout is not surprising as a functional cumulus oophorus is required for oocyte maturation, movement to oviduct and penetration by sperm. [14-16] Notably, mouse and human PTX3 are highly conserved, suggesting that PTX3 may play a similar role in humans. [4] Further supporting the key, non-redundant roles of PTX3 in fertility is the finding that PTX3 is one of the most highly upregulated genes during the pro-inflammatory cascade at the foetal-maternal interface, which is crucial to decidualisation, blastocyst invasion, anchorage and implantation. [17-20]

Pentraxin 3 in twinning

It is clear that PTX3 plays a crucial role in immunity and fertility. Tying all these findings together is  research by Sirugo et al. and May et al. which demonstrate associations between twinning, female fertility and PTX3 SNPs in humans. [3,21] Sirugo et al. demonstrated that the frequency of certain PTX3 haplotypes differed in frequency between mothers of twins and mothers without twins in a sample of 130 Gambian sister pairs (p = 0.006– 3.03×10-6, depending on haplotype). [3] In concordance with this, data from May et al. based on a population study suggest that those findings may indeed be due to increased fertility conferred by the PTX3 mutations. [21] It was found that women with more than12 children had SNPs in PTX3 causing the highest production of PTX3 and that women with less than 2 children had SNPs which conferred the lowest production of PTX3. Specifically, rs6788044 SNP, which was associated with the highest PTX3 production (p = 0.003), was also associated with the highest fertility (p = 0.043). In addition, increased ex vivo LPS-induced PTX3 production, suggesting better immunity, was also associated with increased fertility (p = 0.040). [21]

Conclusion

Taken together, the data suggests that PTX3 may contribute to the high rates of twinning in Sub-Saharan Africa.  As increased PTX3 expression confers improved innate immune response, local selective pressures due to disease may skew epigenetic controls to favour these particular variants in particular populations where a strong immune response is crucial.  [3] Certain SNPs of PTX3 which are selected for also confer increased fertility, via mechanisms such as increased cumulus oophorus stability and regulation of the pro-inflammatory cascade of implantation.  While the role of PTX3 in multiple ovulations – a primary factor of dizygotic twinning – is still unclear, the contribution of PTX3 to successful implantation is also vital to twinning, by increasing the chance of survival of multiple blastocysts. In conclusion, the available evidence suggests that PTX3 may be an important contributor to twinning, at least in some African populations.

Conflict of interest

None declared.

Acknowledgements

I thank God, my family, the Brisbane research team I worked with and my Griffith University lecturers for their guidance and support of me in pursuing a career in medicine and research.

Correspondence

G Yeung: grassy_grace@hotmail.com

References

[1] Hoekstra C, Zhao ZZ, Lambalk CB, Willemsen G, Martin NG, Boomsma DI, et al. Dizygotic twinning. Human reproduction update. 2008;14[1]:37-47.

[2] Bulmer M. The biology of twinning in Man. Oxford, United Kingdom: Oxford Clarendon Press, 1970.

[3] Sirugo G, Edwards DRV, Ryckman KK, Bisseye C, White MJ, Kebbeh B, et al. PTX3 genetic variation and dizygotic twinning in The Gambia: could pleiotropy with innate immunity explain common dizygotic twinning in Africa? Annals of Human Genetics. 2012.

[4] Garlanda C, Bottazzi B, Bastone A, Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annual review of immunology. 2005;23:337-66.

[5] Bottazzi B, Garlanda C, Salvatori G, Jeannin P, Manfredi A, Mantovani A. Pentraxins as a key component of innate immunity. Current opinion in immunology. 2006;18[1]:10-5.

[6] Bottazzi B, Garlanda C, Cotena A, Moalli F, Jaillon S, Deban L, et al. The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunological reviews. 2009;227[1]:9-18.

[7] Reading PC, Bozza S, Gilbertson B, Tate M, Moretti S, Job ER, et al. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. The Journal of Immunology. 2008;180[5]:3391-8.

[8] Bozza S, Bistoni F, Gaziano R, Pitzurra L, Zelante T, Bonifazi P, et al. pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood. 2006;108[10]:3387-96.

[9] Olesen R, Wejse C, Velez DR, Bisseye C, Sodemann M, Aaby P, et al. DC-SIGN [CD209], pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun. 2007;8[6]:456-67.

[10] Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature. 2002;420[6912]:182-6.

[11] Scarchilli L, Camaioni A, Bottazzi B, Negri V, Doni A, Deban L, et al. PTX3 interacts with inter-alpha-trypsin inhibitor: implications for hyaluronan organization and cumulus oophorus expansion. The Journal of biological chemistry. 2007;282[41]:30161-70.

[12] Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, et al. PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development. 2004;131[7]:1577-86.

[13] Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, et al. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol. 2002;16[6]:1154-67.

[14] Wassarman P. The mammalian ovum. Knobil E NJ, editor. New York: Raven Press; 1988.

[15] Yanagimachi R. Mammalian fertilization. Knobil E NJ, editor. New York: Raven Press; 1988.

[16] Tesarik J MOC, Testart J. Effect of the human cumulus oophorus on movement characteristics of human capacitated spermatozoa. J Reprod Fertil. 1990;88:665-75.

[17] Garlanda C, Maina V, Martinez de la Torre Y, Nebuloni M, Locati M. Inflammatory reaction and implantation: the new entries PTX3 and D6. Placenta. 2008;29 Suppl B:129-34.

[18] Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N, et al. Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biology of reproduction. 2007;76[1]:102-17.

[19] Popovici RM, Betzler NK, Krause MS, Luo M, Jauckus J, Germeyer A, et al. Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. Endocrinology. 2006;147[12]:5662-75.

[20] Tranguch S, Chakrabarty A, Guo Y, Wang H, Dey SK. Maternal pentraxin 3 deficiency compromises implantation in mice. Biology of reproduction. 2007;77[3]:425-32.

[21] May L, Kuningas M, Bodegom Dv, Meij HJ, Frolich M, Slagboom PE, et al. Genetic Variation in Pentraxin [PTX] 3 Gene Associates with PTX3 Production and Fertility in Women. Biology of reproduction. 2010;82[2]:299-304.

 

Categories
Letters Articles

Management of high-grade vulvar intraepithelial neoplasia

Vulval intraepithelial neoplasia (VIN) is a condition which is increasingly prevalent, particularly in young women, [1] but is a topic rarely touched upon in medical school. The following article reviews current treatment methods for VIN, both surgical and pharmacological, as well as promising new treatment modalities still being researched.

VIN is a condition in which pre-cancerous changes occur in the vulval skin. The incidence of the diagnosis of VIN is approximately 3/100,000, increasing more than four fold since 1973. [2] Vulvar intraepithelial neoplasia is classified into two main groups based on morphologic and histologic features, consisting of VIN usual group and VIN differentiated type. VIN usual group can be subdivided into basaloid and warty subtypes, typically occurs in younger, premenopausal women and is related to HPV infection and cigarette smoking. VIN differentiated type typically occurs in postmenopausal women and is often associated with lichen sclerosus, which presents as white patches on vulval skin. The rate of progression to invasive vulvar cancer in women with untreated high-grade VIN is reported to range from 9.0 to 18.5%. [3] Half of women with VIN are symptomatic, with pruritis, perineal pain or burning, dysuria, a visible lesion or a palpable abnormality. The lesions themselves are often multifocal, raised and can vary in colour from white to red, gray or brown. Diagnosis involves a colposcopic examination, where VIN lesions produce dense acetowhite lesions with or without punctuation. The goals of treatment are prevention of progression to invasive vulvar cancer and symptom relief, as well as preservation of normal vulvar function and anatomy.

Current surgical therapies include excisional treatments or vulvectomy. The main advantage of excisional therapies over ablative or medical treatment is the ability to make a histopathological diagnosis based on the excised lesion, particularly as occult invasive squamous cell carcinoma is present in many of these women. [4]

Wide local excision is the preferred initial intervention for women in whom clinical or pathologic findings suggest invasive cancer, despite a biopsy diagnosis of VIN, to obtain a specimen for pathologic analysis. [4] Localised high-grade VIN lesions are best managed by superficial local excision of an individual lesion, with reported recurrence rates of 20 to 40%. [5]

Multifocal or extensive lesions that are not amenable to removal with local excision are best removed with a partial or simple vulvectomy. This involves removal of part of or the entire vulva, respectively, together with subcutaneous tissue and perineal tissues if indicated; [5] a last resort as neither normal function nor anatomy are preserved.

Laser ablation therapy is an alternative to excisional therapy, particularly for women with multifocal and extensive disease in whom cancer is not suspected. [6] CO2 laser vaporisation has been shown to be effective in eradicating VIN while achieving good cosmetic and functional results, with success rates of 40 to 75%. [6-7]

A systematic review showed that there were no significant differences in recurrence after vulvectomy, partial vulvectomy, local excision or laser evaporisation. [8]

Medical therapies aimed at preserving the vulvar anatomy are useful in younger patients, provided colposcopic examination and biopsies have excluded invasive disease. The primary medical treatment available is Imiquimod 5% cream, which has antiviral and antitumour effects via stimulation of local cytokine production and cell-mediated immunity. [9] A Cochrane review [1] concluded for women with high grade VIN, Imiquimod was better than placebo in terms of reduction in lesion size and histologic regression. This conclusion was based on the findings of three randomised placebo-controlled trials, with the largest trial reporting a complete response rate of 35% and partial response of 46%. [10] Common side effects reported were erythema, soreness, itching, burning, ulceration and flu-like symptoms; however, these side effects were be reduced by placing patients on an escalating dosing regimen. [1]

Agents such as cidofovir, 5-fluorouracil and photodynamic therapy are currently being investigated as treatment for vulval intraepithelial neoplasia. Cidofovir is an acyclic nucleoside analogue with antiviral activity, and a pilot study shows promising results. [11] 5-fluorouracil is a chemotherapeutic agent that inhibits DNA synthesis, with a review demonstrating a remission rate of 34%; [12] however, this agent is used less commonly in current practice. Photodynamic therapy, whereby a sensitizing agent is applied prior to irradiation of the vulva, has been demonstrated to cause complete response in 33 to 55% of patients with VIN 2-3. [7,13]

The major surgical interventions for VIN appear to be similarly effective and are appropriate when there is desire for a histopathological specimen to exclude invasive cancer. Medical interventions are useful when occult cancer is unlikely and preservation of normal vulvar anatomy is desired. Evidence appears to be strongest for Imiquimod as a conservative medical intervention for the treatment of high grade VIN. Other promising agents include cidofovir, but further investigation through large scale studies is required to characterise the efficacy of these therapies. Diligent follow-up is essential in detecting disease recurrence and monitoring the effectiveness of therapies. More research is needed to develop effective treatment strategies that preserve function and anatomy, particularly as the disease becomes more prevalent in young women.

Conflict of interest

None declared.

Correspondence

S Ai: sylvia.ai3@gmail.com

References

[1] Pepas L, Kaushik S, Bryant A, Nordin A, Dickinson HO. Medical interventions for high grade vulval intraepithelial neoplasia. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No.: CD007924. DOI: 10.1002/14651858.CD007924.pub2.
[2] Judson PL, Habermann EB, Baxter NN, Durham SB, Virnig BA. Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol 2006:107(5):1018-22
[3] Joura EA. Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia. Gynaecol Oncol Path 2002:14(1):39-43
[4] NSW Department of Health. Best Clinical practice gynaecological cancer guidelines 2009. [online]. Accessed on 28/4/2012 from http://www.aci.health.nsw.gov.au/__data/assets/pdf_file/0010/154549/go_clinical_guidelines.pdf
[5] Holschneider CH. Vulval intraepithelial neoplasia. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2012.
[6] Hillemanns P, Wang X, Staehle S, Michels W, Dannecker C. Evaluation of different treatment modalities for vulvar intraepithelial neoplasia (VIN): CO2 laser vaporisation, photodynamic therapy, excision and vulvectomy. Gynecol Oncol 2006:100(2):271-5
[7] Sideri M, Spinaci L, Spolti N, Schettino F. Evaluation of CO2 laser excision or vaporisation for the treatment of vulvar intraepithelial neoplasia. Gynecol Oncol 1999:75:277-81.
[8] Van seters, M, van Beurden, M, de Craen, AJM. Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol 2004:97(2):645-51
[9] Mahto M, Nathan M, O’Mahony C. More than a decade on: review of the use of imiquimod in lower anogenital intraepithelial neoplasia. Int J STDs AIDs 2010:21(1):8-16
[10] Van Seters M, van Beurden M, ten Kate FJW, Beckmann I, Ewing PC, Eijkemans MJC et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. NEJM 2008:358:1465-73
[11] Tristram A, Fiander A. Clinical responses to cidofovir applied topically to women with high grade vulval intraepithelial neoplasia. Gynecol Oncol 2005:99(3):652
[12] Sillman FH, Sedlis A, Boyce JG. A review of lower genital intraepithelial neoplasia and the use of topical 5-fluorouracil. Obstet Gynecol Survey 1985:40(4):190-220
[13] Fehr MK, Hornung R, Schwarz VA, Haller SU, Wyss P. Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid. Gynecol Oncol 2001:80(1):62-6

Categories
Letters Articles

Adult pertussis vaccinations as a preventative method for infant morbidity and mortality

Pertussis, or whooping cough, is a potentially fatal respiratory illness caused by the Bordetella pertussis bacteria. It commonly occurs in infants who have not completed their primary vaccination schedule. [1]

Since 2001, Australia’s coverage rate with the three primary doses of the diphtheria, tetanus and acellular pertussis-containing vaccine (DTPa) at twelve months has been greater than 90%. [2] Despite this high coverage rate, there has been a sharp increase in the incidence of pertussis. In 2008, the Victorian Government received notification of a 56% increase in reported cases (1,644 cases in 2008 compared to 1054 cases in 2007). That same year, New South Wales also reported over 7,500 cases, more than tripling their 2007 total. [3] Given these startling statistics, we must ask ourselves why we are seeing such a significant rise in the incidence of pertussis.

One well researched explanation for this increase is that the pertussis vaccine is not conferring lifelong immunity. A North American study investigating the effectiveness of the pertussis vaccine found that there was a significant increase in laboratory-confirmed cases of clinical pertussis in children aged eight to 13 years. This correlated to the interval after the end of the preschool vaccinations. [4] Other studies have suggested that immunity can wane anywhere between three to 12 years post vaccination, creating ambiguity as to when we become susceptible again. [5,6] This limitation is due to the current non-existence of a clear serologic marker correlating with protection from pertussis. Approximately two years after vaccination, pertussis toxin antibodies have reached minimal levels; however, protection from the disease remains. This suggests immunity is multifactorial. [5]

Despite this, there is widespread agreement that adults with waning immunity and who are in close contact with non-immune infants are a major source of transmission. [6,7] In 2001, a study was published which analysed the source of infection in 140 infants under the age of twelve months who had been hospitalised for pertussis. In the 72 cases where the source of infection could be identified, parents were the source in 53% of cases and siblings accounted for another 22%. [8] The Australian paediatric surveillance unit study of 110 hospitalised infants with pertussis demonstrated adults to be the source in 68% of cases, 60% of which were the parents of the infant in question. [9] Other potential sources that have been identified include grandparents and paediatric health workers. [6]

Since the establishment in 2001 of the international collaboration, the Global Pertussis Initiative (GPI), strategies to decrease the incidence of pertussis have been extensively discussed, with particular emphasis on reducing adult transmission to unprotected infants. [6] In general it has been noted that the control of pertussis requires an increase in immunity in all age groups, especially in adults. [10] Although the GPI agrees that universal adult vaccination would be an effective strategy to protect non-immune infants, this would be too difficult to implement. [2,8] Furthermore, we must be aware that the success of herd immunity is dependent upon the level of population coverage and also the degree of contact between the infected and the non-immune infants. [11]

Due to the difficulties with implementing universal adult vaccinations, more targeted vaccination strategies have been proposed. [10] The concept of a ‘cocoon’ strategy, in which adults in close contact with unprotected infants are given booster vaccinations, [11] has been trialed throughout Australia in various forms. [12] This strategy is simpler to implement, as new parents and family members are easier to access via their contact with health services and their motivation to protect their children. [6] Moreover, because of this motivation, it may be reasonable to assume new parents would be willing to pay for this vaccine out of their own pockets, reducing the economic burden of the increased use of vaccines on our health system.

One model has suggested routine adult vaccination every ten years from the age of 20 years, combined with the ‘cocoon’ strategy of vaccination, would best reduce the rate of infant pertussis infections. However, to date there are no clinical data confirming this strategy to be effective. [11] Furthermore, this particular model is unlikely to receive public funding due to the large expense required.

Another strategy, recently recommended by the Advisory Committee on Immunisation Practices (ACIP), is that of implementing maternal vaccinations. The ACIP reviewed data in 2011 that showed preliminary evidence that there were no adverse effects after the administration of the pertussis vaccine to pregnant women. This strategy would significantly reduce the risk of infection to infants before they were even born. [13]

As one can see, the question of how to increase immunity in our community is complex, given that current strategies are expensive and difficult to implement. As infant deaths from pertussis are easily avoidable, developing effective preventive strategies should be of high priority.

Conflict of interest

None declared.

Correspondence

T Trigger: talia.trigger@my.jcu.edu.au

References

[1] World Health Organisation. Pertussis vaccines: WHO position paper. WHO. 2010; 40: 385-400.
[2] Chuk LR, Lambert SB, May ML, Beard F, Sloots T, Selvey C et al. Pertussis in infants: how to protect the vulnerable. Commun Dis Intell. 2008; 32(4): 449-455.
[3] Fielding J, Simpson K, Heinrich-Morrison K, Lynch P, Hill M, Moloney M et al. Investigation of a sharp increase in notified cases of pertussis in Victoria during 2008. Victorian Infectious Diseases Bulletin. 2009; 12(2): 38-42.
[4] Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in pre-adolescents in a north American outbreak. Clinical Infectious Diseases. 2012; 54(12): 1730-1735.
[5] Wendelboe AM, Van Rie A, Salmaso S, Englund J. Duration of immunity against pertussis after natural infection or vaccination. The Paediatric Infectious Disease Journal. 2005; 24(5).
[6] Forsyth KD, Campins-Marti M, Caro J, Cherry J, Greenberg D, Guiso N et al. New pertussis vaccination strategies beyond infancy: recommendations by the global pertussis initiative. Clinical Infectious Diseases. 2004; 39: 1802-1809.
[7] Spratling R, Carmon M. Pertussis: An overview of the disease, immunization, and trends for nurses. Pediatric Nursing. 2010; 36(5): 239-243.
[8] Jardine A, Conaty SJ, Lowbridge C, Staff M, Vally H. Who gives pertussis to infants? Source of infection for laboratory confirmed cases less than 12 months of age during an epidemic, Sydney, 2009. Commun Diss Intell. 2010; 34(2): 116-121.
[9] Wood N, Quinn HE, McIntyre P, Elliott E. Pertussis in infants: preventing deaths and hospitalisations in the very young. Jounal of Paediatrics and Child Health. 2008; 44(4): 161-165.
[10] Hewlett EL, Edwards KM. Pertussis – not just for kids. The New England Journal Of Medicine. 2005; 352(12): 1215-1223.
[11] McIntyre P, Wood N. Pertussis in early infancy: disease burden and preventive strategies. Current Opinion In Infectious Diseases. 2009; 22: 215-223.
[12] Australian Government Department of Health and Ageing. Pertussis. Australian Immunisation Handbook 9th Edition [Internet]. 2008[cited 2013 Feb19]; 227-239. Available from: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/23041983E698DFB7CA2574E2000F9A05/$File/3.14%20Pertussis.pdf
[13]. Advisory Committee on Immunization Practices (ACIP). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. 2011; 60(41): 1424-1426.

Categories
Letters Articles

A modern, effective and user-friendly approach to medical learning: an overview of spaced repetition programs

Effective and efficient methods of learning are important for medical students to tackle the plethora of information available. A technique that is gaining increasing popularity is Spaced Repetition Learning.

Spaced Repetition Learning (SRL) enhances retention by addressing our poor ability to process and retain information presented en mass at a single point in time. [1] Information is presented at varying time intervals depending on the student’s evaluation of their ability to recall facts. [2] The benefits of this technique have been shown in numerous studies. In mild Alzheimer’s disease, SRL proved useful for improving retention, visual memory and source recognition. [3,4] Another study compared massed versus spaced delivery of information to gastroenterology residents, who on assessment with multiple-choice quizzes showed enhanced long-term retention of facts with SRL. [5] Kerfoot et al also conducted several studies that demonstrated the applicability, efficacy and long-term durability of SRL teaching for urological trainees. [6-8]

Unfortunately, there is relative paucity of randomized trials involving medical students. A handful of studies conducted by Kerfoot et al have shown SRL significantly increases the effectiveness of learning. [9-11] One notable study in particular found that medical students using SRL were able to achieve the same results with significantly reduced study time, thus increasing the efficiency of study. [10] On the contrary, a well-constructed study has disputed the long-term effects of SRL, presenting evidence that the effects are primarily short-term. [12]

Several computer programs readily available use SRL methods, two of which are Anki and Mnemosyne. [13-15] Both programs are free to use (exception: Anki on iOS) and both allow an import and export of data in addition to supporting unicode, images, audio and LaTeX format. Anki also has the capacity to synchronise between devices, support video format and have multiple sides per card (Mnemosyne has a maximum of 3 sides per card). Both programs have cross-platform availability, and data from Mnemosyne is used to aid long-term memory research. [15]

To expand upon the use of Anki, with which the author has had more experience: it is a flashcard program that displays cards at varying intervals depending on how well one feels they have answered them in the past. Comprehensive and easy to understand instructions are available through the website, but in summary, the user writes a question and answer, and saves it to a ‘deck’ of cards. Each question can be labeled with one or more keywords (eg: ‘cardiology’). Cards with a certain label can be reviewed exclusively or excluded from reviews as desired. Decks of cards can also be shared to Anki’s online database or with other individuals. To begin learning without creating a new deck, downloading the “UK Finals Medicine” deck is a good starting point. There is also a varied range of other topics available including foreign languages, geography and musical instrument practice.

When reviewing a deck, the user is presented with a question (Figure 1), answers it (out loud, on paper, in their head) and clicks the mouse to view the answer. The user then grades their performance (Figure 2) and this is when spaced repetition theory is employed. By clicking “Again,” the card will automatically become due at the end of that review session. Clicking “Easy” the first time a particular card is answered will make it due in about a week. Each successive time a card is answered correctly, the card’s due date is pushed further into the future. Useful question examples for a complaint, such as chest pain, may include differential diagnoses, history questions, physical examination and investigations. For a disease, such as COPD, question prompts may include: definition, epidemiology, pathophysiology, aetiology, symptoms, signs, investigations, management, prognosis/staging and complications.

After using Anki for over a year, several benefits have become apparent. It ensures consistent new learning whilst refreshing the student of prior knowledge. Setting review deadlines and adhering to them means one can learn many facts effectively, which saves precious time. Answering questions out loud is perhaps the most effective way to clarify thoughts and consolidate your understanding of a topic. It is also particularly helpful for OSCE examination preparation. Another benefit is the accessibility of Anki, as it is available on most smart phones and can synchronise between devices and computers. The main shortfall of using SRL programs is that its efficacy depends on user commitment.

In summary, Spaced Repetition Learning has been shown to be an effective learning tool in research studies. There are a number of software programs currently available that are user friendly and free to use. From the author’s personal experience and literature review, the success of SRL should certainly be applicable to medical students and I look forward to seeing further objective research in the future to support its use.

Conflict of interest

None declared.

Correspondence

A Lambers: antonlambers@gmail.com

References

[1] Greene RL. Repetition and spacing effects. Learning and memory: A comprehensive reference. 2008;2:65–78.
[2] Baddeley A. Human Memory: Theory and Practice, Revised Edition. Allyn & Bacon; Rev Sub edition; 1997.
[3] Lee SB, Park CS, Jeong JW, Choe JY, Hwang YJ, Park CA, et al. Effects of spaced retrieval training (SRT) on cognitive function in Alzheimer’s disease (AD) patients. Archives of Gerontology and Geriatrics. 2009;49(2):289–93.
[4] Boller B, Jennings JM, Dieudonné B, Verny M, Ergis A-M. Recollection training and transfer effects in Alzheimer’s disease: Effectiveness of the repetition-lag procedure. Brain and Cognition. 2012;78(2):169–77.
[5] Raman M, Mclaughlin K, Violato C, Rostom A, Allard JP, Coderre S. Teaching in small portions dispersed over time enhances long-term knowledge retention. Medical …. Informa UK Ltd UK; 2010.
[6] Kerfoot BP, Baker H. An Online Spaced-Education Game to Teach and Assess Residents: A Multi-Institutional Prospective Trial. Journal of the American College of Surgeons. 2012;214(3):367–73.
[7] Kerfoot BP, Fu Y, Baker H, Connelly D, Ritchey ML, Genega EM. Online Spaced Education Generates Transfer and Improves Long-Term Retention of Diagnostic Skills: A Randomized Controlled Trial. Journal of the American College of Surgeons. 2010;211(3):331–1.
[8] Kerfoot BP. Learning benefits of on-line spaced education persist for 2 years. J. Urol. 2009 Jun;181(6):2671–3.
[9] Kerfoot BP, DeWolf WC, Masser BA, Church PA, Federman DD. Spaced education improves the retention of clinical knowledge by medical students: a randomised controlled trial. Medical Education. 2007 Jan;41(1):23–31.
[10] Kerfoot BP. Adaptive spaced education improves learning efficiency: a randomized controlled trial. J. Urol. 2010 Feb;183(2):678–81.
[11] Kerfoot BP, Brotschi E. Online spaced education to teach urology to medical students: a multi-institutional randomized trial. The American Journal of Surgery. 2009 Jan;197(1):89–95.
[12] Schmidmaier R, Ebersbach R, Schiller M. Using electronic flashcards to promote learning in medical students: retesting versus restudying. Medical Education. 2011.
[13]  Flashcard Software Comparison – Wikipedia [Internet]. [cited 2013 Feb 20]. Available from: http://en.wikipedia.org/wiki/List_of_flashcard_software
[14] Elmes D. Anki [Internet]. [cited 2013 Feb 20]. 2nd ed. GNUAGPLv3. Available from: http://ankisrs.net/
[15] Bienstman P. Mnemosyne [Internet]. [cited 2013 Feb 20]. 2nd ed. GPLv2. Available from: http://www.mnemosyne-proj.org/

Categories
Feature Articles Articles

The role of Aboriginal Community Controlled Health Services in Indigenous health

“Our right to take back responsibility.” Noel Pearson, 2000 [1]

This emotive aphorism by Pearson embodies the struggle of Australia’s Indigenous people to gain control of their destiny, which for generations has been wrested from them into the power of governments. Although his statement was primarily directed toward welfare, the same right of responsibility can be applied to health, perhaps the gravest challenge facing the Aboriginal population. As Pearson alluded to, the only way to solve the health crisis is by enabling local communities to take charge of their own affairs. This principle of self-determination has led to the creation of Aboriginal Community Controlled Health Services (ACCHS), which has allowed over 150 Aboriginal communities throughout Australia control over their healthcare. [2] This article describes the founding principles behind community controlled health centres in Aboriginal communities through considering several different ACCHS and the unique challenges they face.

The fundamental concept behind each ACCHS – whether metropolitan, rural or remote – is the establishment of a primary healthcare facility that is both built and run by the local Aboriginal people “to deliver holistic, comprehensive, and culturally appropriate health care to the community which controls it.” [2] This is based upon the principle of self-determination and grants local people the power to achieve their own goals. From the beginning ACCHS were always intended to be more than exclusively a healthcare centre and each ACCHS has four key roles: the provision of primary clinical care, community support, special needs programmes, and advocacy.

ACCHS endeavour to provide primary healthcare as enshrined by the World Health Organization in the 1978 Declaration of Alma-Ata. This landmark international conference defined primary healthcare as:

“essential health care based on practical, scientifically sound and socially acceptable methods and technology made universally accessible to individuals and families in the community through their full participation and at a cost that the community and the country can afford to maintain… in the spirit of self-determination.” [3]

Although conceived subsequent to the advent of the community controlled healthcare movement in Australia, this definition echoes many of the underlying principles upon which ACCHS were founded, including the most important aspect – local control. Indeed, it is widely accepted throughout the literature that the community itself must identify its needs and problems so an effective and appropriate course of action can be undertaken. [4-7]

This principle is espoused in the National Aboriginal Health Strategy’s frequently quoted statement that “Aboriginal health is not just the physical well-being of an individual but the social, emotional and cultural well-being of the whole community in which each individual is able to achieve their full potential thereby bringing about the total well-being of their community.” [8] The notion of ‘community’ is an essential component of the Indigenous view of the self and therefore strongly related to health and well-being. Accordingly, ACCHS have a holistic view of healthcare, recognising that Indigenous healthcare needs to be multi-faceted and focus on cultural complexities that may not be appreciated by mainstream health services. As each Aboriginal community across the country has a distinct culture and language, [9] local control is paramount.

The concept of community control is not new. It can be traced back to early nineteenth-century America, where such services were used with success for improving the health of the poor and recent migrants. [4] The first ACCHS was established in the inner city Sydney suburb of Redfern in 1971. [10] Known as the Aboriginal Medical Service (AMS), it pioneered the concept of community controlled healthcare in Australia and, from modest beginnings, has now expanded into a major, versatile healthcare facility that provides free medical, dental, psychological, antenatal and drug and alcohol services to the large Aboriginal community in Sydney. Redfern’s AMS overcame struggles against an initially distrustful and paternalistic government through the dedication of visionary Indigenous leaders and support of benevolent non-Indigenous Australians. [10,11]

Specialised Indigenous policies are essential, as it is impossible to apply the same approach that is used in health services for non-Indigenous patients. Many Indigenous people are uncomfortable with seeking medical help at hospitals or general practices and therefore are reluctant to obtain essential care. [12] In addition, access to healthcare is often extremely difficult due to either geographical isolation or lack of transportation. Many Indigenous people live below the poverty line, so the services provided by practices that do not bulk bill are unattainable. Mainstream services struggle to provide appropriate healthcare to Aboriginal patients due to significant cultural and language disparities; [5,13] the establishment of ACCHS attempts to overcome such challenges.

For example, the Inala Indigenous Health Service in south-west Brisbane performed extensive market research to determine the factors keeping Aboriginal patients from utilising the mainstream health service. The results showed that several simple measures were highly effective in engaging the local community, such as employing an Indigenous receptionist and making the waiting room more culturally appropriate through local art or broadcasting an Aboriginal radio station. [12] In the five years following implementation of these strategies, the number of Indigenous patients at Inala ballooned from 12 to 899, and an average of four consultations per patient per year was attained, compared to the national Indigenous average of fewer than two. [14] A follow-up survey attributed patient satisfaction to the presence of Indigenous staff and a focus on Indigenous health. [12]

Nevertheless, the consequence of  longstanding obstacles to Indigenous access to mainstream healthcare is manifest in the stark inequity between the health outcomes of Indigenous and non-Indigenous Australians. The most recent data from the Australian Institute of Health and Welfare (AIHW) shows that the discrepancy in life expectancy between Aboriginal Australians and their non-Indigenous counterparts remains unacceptably high, at 11.5 years for males and 9.7 for females. [15] Moreover, studies demonstrate that Aboriginal people have significantly worse outcomes in key health indicators, including infant mortality, diabetes, heart disease, infectious disease and mental illness. [5,12,13,16] Such disparities indicate that a novel, tailored approach to Indigenous health is required.

Cultural understanding is essential, as demonstrated by the example of the Anyinginyi Health Aboriginal Corporation in the Northern Territory. Anyinginyi serves the twelve remote Aboriginal communities within a 100km radius of Tennant Creek and its name comes from the local Warumungu language, meaning ‘belonging to us’ [17] emphasising the community’s control of, and pride in, this service. Anyinginyi has always strived to be more than just a health service and has evolved to deliver many other community programmes. This is embodied by Anyinginyi’s insistence on ‘culturally appropriate’ healthcare for Aboriginal people. In addition to medical advice, the local Aboriginal community is offered support through various programmes that range from employment services to cultural and spiritual activities promoting Indigenous language and culture. One such social service is the ‘Piliyintinji-Ki Stronger Families’ initiative, which assists community members through access to support services relating to issues such as family violence and the Stolen Generations. [17] Indeed, ACCHS such as Anyinginyi have the additional benefit of providing employment opportunities for community members, as the vast majority of the employees are Indigenous. All new staff members participate in a Cross Cultural Workshop, as one of Anyinginyi’s goals is to ensure that the local Aboriginal cultures are respected and continue to thrive.

The other important arm of healthcare in ACCHS relates to population health, with initiatives ranging from education campaigns to immunisations and screening for diseases. [2] One of the first large-scale community health promotion campaigns run specifically for Aboriginal people was conducted by the Redfern AMS between 1983-1984 to encourage breast-feeding among the local Koori mothers. [11] It achieved such stunning success that it set a precedent for all future ACCHS to continue in the important area of preventative medicine, with similar campaigns for sexual health and safe alcohol consumption having been undertaken subsequently.

Moreover, each ACCHS runs special services that are dictated by local needs and priorities. In some instances, there is a specific health problem that needs to be addressed, such as poor nutrition or substance abuse. Other programmes are directed at specific groups, such as young mothers or the elderly. The flexibility of these special services allows each ACCHS to identify and address the most significant problems within its area – problems that can only be identified by the community itself. For example, the Danila Dilba Health Service in Darwin runs a programme called ‘Dare to Dream’ that provides support and counselling for young Indigenous people suffering from mental illness. [18] It is an early intervention programme that intends to identify and support adolescents exhibiting early signs of both behavioural and mental health problems. To this end, school visits are undertaken to promote awareness of mental health issues to students and staff, as well as the services that Danila Dilba has to offer. A ‘chillout’ centre has been set up in Darwin as a safe place for young people to come and allows the community workers to refer those who present to appropriate counselling services. As such, Danila Dilba is empowered to proactively address an important local issue in the most culturally-appropriate way.

ACCHS are also active in the area of advocacy. This involves providing a voice for the community so that their needs can be expressed. Although each ACCHS operates autonomously, they form a national network with their collective interests represented both on a state/territory level and also nationally. Each of the eight states and territories has a peak representative body that acts on behalf of all ACCHS within that jurisdiction. [2] Examples of these organisations include the Aboriginal Health & Medical Research Council of New South Wales and the Aboriginal Medical Services Alliance Northern Territory. At the national level the umbrella body overseeing all the different stakeholders across the country is the National Aboriginal Community Controlled Health Organisation (NACCHO). [2] Individual ACCHS, as well as NACCHO and the affiliated state or territory peak bodies, lobby all levels of government for increased funding and greater recognition of the issues facing Aboriginal communities. The collective weight of NACCHO as a national advocate allows each community’s needs to be heard.

Inevitably, the scope of the services each ACCHS can provide is restricted by funding, most of which comes from the Commonwealth or State and Territory Governments. [2] More money continues to be spent per capita on mainstream health services than on Aboriginal health, despite the great dichotomy in health outcomes. Indeed, the 2012 Indigenous Expenditure Report published figures showing that for every dollar spent on healthcare subsidies for non-Indigenous health, only $0.66 is spent on Aboriginal health. [19] This statistic covers all the key areas of healthcare expenditure, such as Medicare rebates, the pharmaceutical benefits scheme (PBS) and private health insurance rebates. Therefore, Indigenous patients are not receiving the same level of health service delivery, including clinical consultations and treatment, compared to their non-Indigenous counterparts. However, it is propitious to note that the funding bodies have recognised the value of the public health efforts of ACCHS, as the spending in this area is a $4.89 to $1.00 ratio in favour of Indigenous health. [19] Nevertheless, the priority needs to be placed on ensuring that sufficient funding exists to allow Indigenous patients to access health care subsidies as required.

In addition to inadequate funding, another major obstacle that ACCHS face is the difficulty in attracting and retaining doctors and allied health professionals. According to the AIHW’s most recent report, only 63% of Indigenous health services currently employ a doctor. [20] Consequently, a significant increase in the number of general practitioners working with Indigenous patients is required simply to provide adequate services. There is additionally a severe lack of Aboriginal medical students and general practitioners, which limits the opportunities for Indigenous professionals to provide culturally-appropriate care to their own communities. Census data from 2006 found that there were 106 Indigenous doctors nationally, accounting for only 0.19% of all medical practitioners. [21] These shortages are compounded further for ACCHS in rural and remote areas. By 2011, further data from Medical Deans demonstrated that the numbers had increased to 153 Indigenous medical practitioners nationally, along with 218 enrolled Indigenous medical students. Although promising, these numbers remain grossly inadequate to fulfil workforce demand. [22]

Services become stretched due to perpetual resource inadequacies. Understandably, the remoteness of some communities makes service delivery challenging, yet even major metropolitan areas with large Indigenous populations can struggle to adequately provide for those in their catchment area. Under-resourcing places major constraints on service delivery and different ACCHS throughout the country exhibit significant variation in the level of services offered. Some are large, employ several doctors and provide a wide range of services; others are much smaller and operate without doctors. [20] These rely on Aboriginal health workers and nurses to provide the bulk of primary healthcare.

As such, the success of the ACCHS concept would not have been possible without the contribution of Aboriginal health workers. The role of Aboriginal health workers, who are often sourced from the local community, is to provide the primary healthcare that ACCHS offer. [23] This involves assessing patients and then coordinating or providing the medical attention required. Health workers are able to treat certain conditions with the help of standard treatment guidelines and provide a selection of important medications to patients. Importantly, Aboriginal health workers have a liaison role between medical professionals and Aboriginal patients. They are often required to act as an interpreter between the patient and health professional, thus providing an intermediary for cross-cultural interactions, and therefore improving the quality of healthcare provided to the local community.

Due to the often quite remote locations of ACCHS and the scarcity of doctors and nurses, Aboriginal health workers perform many clinical tasks that would be provided by a medical professional in mainstream health services. Aboriginal health workers bear much greater responsibility than their colleagues in the public sector and often learn a wide range of procedural skills including how to perform standard health checks, vaccinations and venepuncture. [23] Indeed, some choose to specialise in a specific area (such as diabetes, pregnancy or infant care) thus gaining additional skills and responsibilities. Still others take on managerial responsibilities. This is in contrast to the public sector, where health workers are often fixed to one routine area or even to non-clinical work such as transportation or social assistance. [23] Without Aboriginal health workers performing these additional tasks, ACCHS would not be able to provide a sufficient level of service for the community. For this reason, Aboriginal health workers are rightly considered the backbone of community controlled health services.

As one example, the Pika Wiya Health Service in the South Australian town of Port Augusta runs two outreach clinics for communities in Copely and Nepabunna. Due to the shortage of doctors, these clinics are staffed entirely by Aboriginal health workers. Their invaluable contribution is evident, with 695 clinical encounters performed by health workers during 2008, [24] ensuring that the absence of doctors did not deny the local people the chance to receive healthcare. Whilst the major health issues faced by Indigenous people are broadly similar between urban and remote communities, these problems are often compounded by the remoteness of the location. Although these are challenges that Copely and Nepabunna will continue to have to face, the empowerment of Aboriginal health workers has helped redefine the direction of Pika Wiya’s outreach health services.

Aboriginal health workers face many difficulties. Perhaps the most significant is that, until recently, there had been no national qualifications or recognition of the skills they developed. [23] The introduction of national registration for Aboriginal health workers (from July 1 2012) and the new qualification of Certificate IV in Aboriginal and Torres Strait Islander Primary Health Care (Practice) have revolutionised the industry. [25] This has had the benefit of standardising the quality and safety of the Aboriginal health worker labour force. However, as the changes will increase the required length and standard of training, there is the potential for current or prospective health workers to be deterred by the prospect of undertaking study at a tertiary level, particularly if they have had limited previous education. Nevertheless, national registration is a positive step for recognising the important work done by Aboriginal health workers, and in providing them with the training to continue serving their communities.

In addition to doctors, nurses and health workers, medical students are also important stakeholders in Indigenous health. First, much has been done in recent years to increase the numbers of Indigenous medical students. For example, the University of Newcastle has been the first medical school to make a dedicated attempt at training Indigenous doctors and has produced approximately 60% of Australia’s Indigenous medical practitioners. [26] This achievement has been based on a “strong focus on community, equity and engagement by the medical profession.” [26] Encouraging community members to enter the profession can be an important way of addressing both the lack of doctors in Indigenous communities and paucity of doctors of Indigenous background. The benefits are broader than this, as Indigenous doctors provide strong role models for young Indigenous people and also have the opportunity to contribute with advocacy and leadership within Indigenous health.

Secondly, the medical student population as a whole is exposed to increasingly more Indigenous health as part of the core curriculum at university following adoption of the updated Australian Medical Council accreditation standards from 2007. [27] Additionally, some students even have the opportunity to spend time in an ACCHS and experience first-hand how the system works. There has been some criticism of these ‘fly in, fly out’ medical electives, where students are sent to ACCHS for short periods and then leave. [28] Whilst this model may be beneficial for the student, it fails to engage the local community as they are unable to build meaningful or lasting relationships with the student.

Better models allow for a longer-term placement and immersion in the community. These include the John Flynn Placement Programme where some students are able to spend a fortnight annually in an ACCHS in the Northern Territory over a period of four years. [29] Another example is the Northern Territory Clinical School, which allows third-year medical students from Flinders University to spend a whole year of study in Darwin, providing the opportunity for increased contact with local Indigenous communities. [30] Initiatives such as these help to build a relationship with the community, and allows for increased acceptance of the medical student. Additionally, the student is able to make a more meaningful contribution to various client’s healthcare. Prolonged or longitudinal attachments have also been shown to increase the likelihood of students returning as a doctor. [31] Certainly, there is much scope for the contribution of medical students to be harnessed more effectively.

It is abundantly apparent that any solution to address the health inequalities of Aboriginal people will only be effective if it recognises that the local Aboriginal communities must control the process of healthcare delivery. This is the principle upon which ACCHS were founded and can be attributed to their many successes, as demonstrated through the examples of Redfern’s AMS, Inala, Anyinginyi, Danila Dilba and Pika Wiya. In spite of the challenges posed by inadequate funding, under-staffing and often remote locations, these organisations strive to uphold the ideals of self-determination and community control. It is hoped that wider adoption of these principles by national governing bodies together with improved financial support will enable Indigenous Australians control over their lives and destinies, leading to better health outcomes.

Conflict of interest

None declared.

Acknowledgements

The author would like to thank the Australasian Faculty of Public Health Medicine for their generous support of this research through awarding the 2011 John Snow Scholarship for South Australia. Additionally, the author wishes to acknowledge the guidance of Dr Doug Shaw when preparing this work for presentation at the 2012 Population Health Congress.

Correspondence

M Weightman: michael.weightman@student.adelaide.edu.au

References

[1] Pearson N. Our right to take responsibility. Cairns, Queensland:  Noel Pearson and Associates; 2000.

[2] National Aboriginal Community Controlled Health Organisation. 2010-2011 Annual Report. Canberra, ACT: NACCHO; 2011.

[3] World Health Organisation. Declaration of Alma-Ata. Alma-Ata, USSR: WHO; 1978.

[4] Minkler M, Wallerstein N. Improving health through community organisation and community building: a health education perspective. In Minkler M, editor. Community organizing and community building for health. New Brunswick, USA: Rutgers University Press; 1998, 26-50.

[5] Stephens C, Nettleton C, Porter J, Willis R, Clark S. Indigenous peoples’ health – why are they behind everyone, everywhere? Lancet. 2005; 366(9479): 10-13.

[6] Horton R. Indigenous peoples: time to act now for equity and health. Lancet. 2006; 367(9524): 1705-1707.

[7] King M, Smith A, Gracey M. Indigenous health part 2: the underlying causes of the health gap. Lancet. 2009; 374(9683): 76-85.

[8] National Aboriginal Health Strategy Working Party. A national Aboriginal health strategy. Canberra, ACT: National Aboriginal Health Strategy Working Party; 1989.

[9] Burgess CP, Johnston FH, Berry HL, McDonnell J, Yibarbuk D, Gunabarra C, et al. Healthy country, healthy people: the relationship between Indigenous health status and ‘caring for country.’ Med J Aust. 2009; 190(10): 567-572.

[10] Marles E, Frame C, Royce M. The Aboriginal Medical Service Redfern: improving access to primary care for over 40 years. Aust Fam Physician. 2012; 41(6): 433-436.

[11] Foley G. Redfern Aboriginal Medical Service: 20 years on. Aborig Isl Health Work J. 1991; 15(4): 4-8.

[12] Hayman NE, White NE, Spurling GK. Improving Indigenous patients’ access to mainstream health services: the Inala experience. Med J Aust. 2009; 190 (10): 604-606.

[13] Zhao Y, Dempsey K. Causes of inequality in life expectancy between Indigenous and non-Indigenous people in the Northern Territory, 1981-2000: a decomposition analysis. Med J Aust. 2006; 184(10): 490-494.

[14] Deeble J. Expenditure on health services for Aboriginal and Torres Strait Islander People. Canberra, ACT: Department of Health and Family Services; 1998.

[15] Australian Institute of Health and Welfare. The health and welfare of Australia’s Aboriginal and Torres Strait Islander people: an overview 2011. Canberra, ACT: Australian Institute of Health and Welfare; 2011.

[16] Anderson I, Crengle S, Kamaka ML, Chen T-H, Palafox N, Jackson-Pulver L. Indigenous health in Australia, New Zealand, and the Pacific. Lancet. 2006; 367(9524): 1775-1785.

[17] Anyinginyi Health Aboriginal Corporation. 10/11 Annual Report. Tennant Creek, NT: Anyinginyi Health Aboriginal Corporation; 2011.

[18] Danila Dilba Biluru Butji Binnilutlum Health Service Aboriginal Corporation. Annual Report 2010. Darwim, NT: Danila Dilba Biluru Butji Binnilutlum Health Service Aboriginal Corporation; 2010.

[19] Steering Committee for the Review of Government Service Provision. 2012 Indigenous expenditure report: overview. Canberra, ACT: Productivity Commission; 2012.

[20] Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander health services report, 2010-11: OATSIH services reporting – key results. Canberra, ACT: Australian Institute of Health and Welfare; 2012.

[21] Australian Bureau of Statistics. Population distribution, Aboriginal and Torres Strait Islander Australians, cat. no. 4705.0. Canberra, ACT: Australian Bureau of Statistics; 2007.

[22] Cavanagh J. Medical Deans – AIDA: national medical education review. Canberra, ACT: Medical Deans Australia and New Zealand, Australian Indigenous Doctors’ Association; 2012.

[23] Mitchell M, Hussey LM. The Aboriginal health worker. Med J Aust. 2006; 184(10): 529-530.

[24] Pika Wiya Health Service Inc. Annual Report for Year 2007-2008. Port Augusta, SA: Pika Wiya Health Service Inc; 2008.

[25] Health Workforce Australia. Growing our future: the Aboriginal and Torres Strait Islander Health Worker project final report. Adelaide, South Australia: Health Workforce Australia; 2011.

[26] Lawson KA, Armstrong RM, Van Der Weyden MB. Training Indigenous doctors for Australia: shooting for goal. Med J Aust. 2007; 186(10): 547-550.

[27] Australian Medical Council. Assessment and accreditation of medical schools: standards and procedures. Part 2. Educational standards. Canberra, ACT: Australian Medical Council; 2006.

[28] Crump JA, Sugarman J. Ethical considerations for short-term experiences by trainees in global health. JAMA. 2008; 300(12): 1456-1458.

[29] Young L, Kent L, Walters L. The John Flynn Placement Program: evidence for repeated rural exposure for medical students. Aust J Rural Health. 2011; 19(3): 147–153.

[30] McDonnel Smedts A, Lowe MP. Efficiency of clinical training at the Northern Territory Clinical School: placement length and rate of return for internship. Med J Aust. 2008; 189(3): 166-168.

[31] Denz-Penhey H, Shannon S, Murdoch JC, Newbury J. Do benefits accrue from longer rotations for students in rural clinical schools? Rural Remote Health. 2005; 5(2): 414.

Categories
Articles Book Reviews

Perhaps the only ECG text you need….

Jayasinghe, S. Rohan. ECG Workbook, Australia: Elsevier; 2012.
RRP: $59.95

This is an Elsevier supported book review

Like tools are to a plumber, correct ECG interpretations are to a doctor. ECGs are the basis of diagnosis for many of the patients that walk through our hospital doors. Consider this: how many patients do you see that don’t have an ECG tucked into their notes?  And how often have you looked at an ECG and quietly thought to yourself, “what on earth is going on?” before sheepishly praying that the consultant doesn’t ask you to interpret it? Mastering an ECG is the foundation of being a doctor, an essential skill that you will not be able to shy away from. So in a quest to find a tool that would ease my ECG fears, I stumbled across this clever little book.

Jayasinghe takes both a logical and systematic approach in this text as he emphasizes the “importance of treating a patient and not an ECG”. Readers are provided with real life case studies and guided through a stepwise process to interpret an ECG. This provides an opportunity to not only practice this new skill set but also to formulate a clinical diagnosis and decide on appropriate and optimal management.

The workbook is divided into three convenient user-friendly sections.

Section 1 takes readers on a journey through the fundamentals of ECGs. Essential knowledge on cardiac conduction physiology is revisited, before explaining the derivation of the modern electrocardiogram by the Nobel prize-winning Dutch physician William Eithoven. Difficult concepts (for example, the accurate determination of the cardiac axis) are explained using both the two and three lead method. This is discussed before using a difficult yet more accurate methodical explanation of its relation to a hexa-axial reference system. The importance of correct limb placement is clarified before the author dives into providing the reader with six practical rules that should be applied when ‘eyeballing’ any ECG. This framework then provides an organized line of attack when attempting to read an ECG. Overall Section 1 studies the ‘normal’ ECG and highlights life-threatening ECG changes that require urgent therapeutic intervention.

Section 2 explores ECG based diagnosis through interpreting pathological ECGs, highlighting areas of study such as abnormalities in the P wave, PR segment, QRS complex, Q wave, R wave, S wave and ST segments. This section then focuses on STEMI associated ECG changes. The author should be commended for including pathologies with mixed ECG changes which are commonly seen in clinical settings such as pulmonary embolism, subarachnoid haemorrhage, takotsubo cardiomyopathy, hypokalaemia and hyperkalaemia before drawing the reader’s attention to drug induced ECG changes.

Everyone knows that practice makes perfect and that the key to mastering any new skill set is practice. The final section of this innovative book is clearly set out in workbook format containing a series of ECG tracings linked to a clinical scenario. A fill in worksheet guides the reader to interpret the ECG using the strategic framework taught in Section 1.

Many texts that attempt to help the reader master the art of ECG interpretation lack this crucial worksheet approach, which facilitates repetitive learning and ultimately allows the student to master the ability to interpret ECGs in the clinical context. Each case is followed by the answer, which has been carefully set out in the same systematic framework taught throughout the text. The author has clearly placed much effort into ensuring that the reader understands the importance of using a stepwise approach when faced with this somewhat daunting task. Additionally, the author endeavours to engage readers to teach them to stratify the significance of the ECG findings based on clinical relevance and urgency. This is a refreshing approach from a medical textbook.

Self assessment enables the reader to build confidence and precision, to gauge their competence and to hone weaknesses. Key concepts can be revisited and mastered as they work their way through this glorious all-in-one paperback.

This short but sweet text provides a comprehensive and systematic approach to learning ECG interpretation whilst ensuring relevancy to real life scenarios. The only criticism I have of this clever little lifesaver, which is small enough to effortlessly carry around hospital, is that it should be available in hard-back! All things considered, the author, an interventional cardiologist, should be applauded as he has succeeded in providing readers with the perfect balance of mastering the art of ECG interpretation whilst being able to apply it to diagnostic situations without getting lost in the detail.

Correspondence

A Lalji: liyah10@hotmail.com

 

Categories
Review Articles Articles

The benefits associated with male HPV vaccination in Australia

Background: Human papillomavirus (HPV) is a family of highly contagious sexually transmitted viruses which are associated with the development of genital warts and certain HPV related cancers in males and females. After conducting a cost-effective analysis, the Australian Government has decided to expand the school based female only HPV vaccination program to include males commencing in 2013. Methods: A search of Ovid MEDLINE, The Cochrane Library, Google Scholar, BMJ Journals, and JSTOR was undertaken. Discussion: HPV vaccination has proven to have a high safety profile with sustained efficacy rates. Male vaccination will not only offer immunity to its recipients but also provide indirect protection to both sexes and high risk groups through herd immunity. The included high risk HPV strains 16 and 18 are associated with more than 70% of cervical cancers, 80% of anal cancers, 25% of penile cancers and 31% of oropharyngeal cancers worldwide. The quadrivalent vaccine also covers HPV 6 and 11 which are responsible for 90% of genital warts. Conclusion: Robust monitoring and surveillance systems are in place which will enable Australia to quantify the impacts of HPV vaccination in the future. Models show that the rates of HPV infection will further reduce by an additional 24% in 2050 compared to female vaccination alone, if vaccination rates for boys reach the same levels attained by girls in 2011. This will result in a significant decrease in the clinical burden of HPV-related diseases, the associated costs of treatment, and the psychological trauma which often accompanies the diagnosis of an HPV-related condition.

Introduction

Human papillomavirus (HPV) is a highly contagious family of viruses with over 150 distinct genotypes. [1] The virus infects the squamous epithelium in both males and females, with over 40 genotypes affecting the anogenital region. [2-4] HPV is usually a transient, asymptomatic infection which is transmitted through skin-to-skin contact associated with sexual activity, and the risk of infection increases with a greater number of sexual partners. [2-5] HPV is also the most common sexually transmitted infection (STI), [6] with up to 80% of people being infected with at least one type of genital HPV in their lifetime. [3,7,8]

There is a proven association establishing the relationship between persistent HPV infection and the development of pre-cancerous (CIN) and cancerous lesions in females. [7] Australia was the first of many countries to create a National HPV Vaccination Program for females, and has been providing the school based HPV vaccination to 12-13 year old girls since 2007. [9,10] Males are expected to join their female counterparts commencing in February 2013. [11,12]

Australia provides this vaccination in the form of the quadrivalent Gardasil® vaccine which covers four types of HPV (6, 11, 16 and 18). [8] In women, although there are many ‘high risk’ types, HPV 16 and 18 alone are associated with 70% of cervical cancers, [2,3,13] and 32% of vaginal cancers worldwide. [14] In men and women, those two types also contribute to over 80% of anal cancers, 24% of oral cancers, and 31% of oropharyngeal cancers. [6,14] Furthermore HPV 16 and 18 account for 90% of all HPV attributable male cancers. [5]

The other two HPV types covered by the quadrivalent vaccine, HPV 6 and 11, are associated with 90% of genital warts and 100% of juvenile onset recurrent respiratory papillomatosis (RRP) cases, resulting in a severe respiratory condition. [14] Recent studies also reveal that more than 4% of all cancers worldwide may be caused by HPV. [15,16]

On the back of such evidence, the Australian Government has announced the introduction of the quadrivalent HPV vaccination for males in the 12 -13 age group, with a catch-up program for males aged 14-15 years at school. [11,12] Early data show that 73% of females in the 12-13 age group received the full course of three doses (Figure 1). This level of coverage is significantly higher than the levels in the catch up programs where the lowest level is 30% in the 20-26 year old age group. Therefore, introducing an immunisation program for boys is a significant move towards preventing the many HPV attributable cancers and genital warts by accelerating coverage and the levels of herd immunity against HPV.

Therefore, the aim of this article is to examine the evidence which exists globally in supporting HPV vaccination and to identify any additional benefits routine male vaccination may provide. The article will also consider high risk population groups, the cost effectiveness of widespread HPV vaccination and the long term monitoring goals for the Australian vaccination program.

Methods

The review of the literature was undertaken through a search of Ovid MEDLINE, The Cochrane Library, Google Scholar, BMJ Journals, and JSTOR. The search aimed to find original research articles, reviews, case studies, and opinion pieces that related to HPV vaccinations and the spread of sexually transmitted infections. The terms used in our search ensured we reviewed a broad range of relevant studies. These terms were: ‘human papilloma virus’, ‘males’, ‘quadrivalent’, ‘vaccine’, ‘sexually transmitted disease’, ‘cervical cancer’, ‘penile carcinoma’, ‘herd immunity’, ‘genital warts’, ‘cost effectiveness’ and ‘pap smear’. We also sought to review the ‘grey literature’, and therefore searched a broad range of internet sources, including government websites. These were accessed for up-to-date information on the HPV vaccination program, the cervical screening program, and relevant legislation. The studies were limited to those published in the English language after the year 2000.

Using the methodology described above, 63 articles and documents found during the search were selected for consideration. After individually analysing all the identified documents, 39 publications were selected for inclusion in the final review with preference given to more recent publications and those with data which could be applied to the Australian program. Of these remaining publications, 16 were original research articles, 15 were review articles, 6 were Australian Government reports or legislation, 1 was a professional communication, and 1 was a media release. The remaining 24 publications were excluded as they were assessed as not relevant to the Australian program.

Discussion

Evidence for HPV vaccination in men

HPV vaccinations worldwide has revealed no major safety concerns, [5] and recent clinical trial data show that the safety profile for males is the same as for females. [18] The most commonly reported side effects have been mild and include fever, nausea and localised injection site pain. [19] Furthermore, there have been no reported deaths that are directly attributable to the vaccine. [5,20]

Currently, only the quadrivalent vaccine has demonstrated protective effects for males in clinical trials. [18] Boys vaccinated with the quadrivalent vaccine have the same seroconversion rates as girls, which is as high at 99%. [21] In addition, the current implementation of the HPV vaccination program for girls in Australia does not have full coverage. [8] Vaccinating males will provide indirect protection to the targeted females in the school HPV vaccination program who were not fully vaccinated, by increasing herd immunity. [8] This protection is vital because there is good evidence that vaccines which include HPV 16 and 18 prevent persistent HPV infections and precancerous cervical, vulvar, and vaginal lesions in females. [14]

Therefore, the inclusion of males into the HPV vaccination program will provide them, and possibly their unvaccinated sexual partners, with protection from HPV. [14] This will also result in higher levels of herd immunity, which refers to the protective effect offered to the unvaccinated and susceptible population by having high rates of acquired immunity in the vaccinated population. [22] This phenomenon acts to limit the cases of transmission and the reservoirs of disease. One example of herd immunity is the widespread vaccination of males against rubella even though the virus is of little clinical significance in males. This vaccination program in Australia has led to a significant reduction in the transmission of rubella to susceptible pregnant females and the subsequent development of congenital rubella syndrome. [6,23]

Male vaccination not only provides direct protection to its recipients, it also further reduces rates of transmission [5] and provides indirect population benefits to protect members of both sexes through herd immunity. [24] A retrospective seminal study across Australia compared rates of genital warts before and after female vaccination and post immunisation in the 2004-2009 time period. Results demonstrated a 59% decrease in genital warts in age matched females who were eligible for free vaccination and a corresponding decrease of 28% in heterosexual males in the same age bracket who were ineligible for free vaccination. [25] These trends were supported by another Melbourne study which reported the near disappearance of genital warts in heterosexual females and males under 21 years of age. [26] These studies provide early evidence of the benefits of vaccination providing herd immunity which has reduced the clinical burden of genital warts, the high costs of treatment, [27] and the psychological impact associated with the condition. [28,29]

However, the impact of genital warts in the Australian community can be further reduced. One model of HPV transmission suggests that if vaccination rates for boys reached the same 73% level attained by girls in 2011, then by 2050 the vaccination of boys would have prevented an additional 24% of new HPV infections. [5] Other mathematical models suggest that while vaccination of 12 year old girls alone would reduce the incidence of genital warts by 83% and cervical cancer by 78%, including boys in the vaccination program would reduce the incidence of genital warts by 97% and cervical cancer by 91%. [30]

The vaccination of males would not only help the female population, but would also reduce the disease burden for males. This was demonstrated in study of 4065 healthy boys which demonstrated a clear reduction in the development of external genital lesions. [18] One month after the boys received their third and final vaccination,
seroconversion for all four types of HPV had occurred in 97.4% of boys, with an additional 1.5% of the cohort seroconverting for only three types of the four. [18] Vaccination was shown to reduce the incidence of external genital lesions, due to infection with HPV types 6, 11, 16 and 18, by 90.4% in the per-protocol population. [18]

Nonetheless, the lack of long term data means there is currently no clinical evidence demonstrating a reduction in HPV related male cancers after vaccination. However, two of the quadrivalent vaccine types, HPV16 and HPV18, are responsible for 90% of all HPV attributable cancers in men. [5] Therefore, since the quadrivalent vaccine has demonstrated a reduction in high grade cervical lesions in women, [8] there is an expectation that vaccination will have the same effect for cancers in men. [8,31] Worldwide, HPV types 16 and 18 are associated with over 80% of anal cancers, 25% of penile cancers [6,14,15] and 31% of oropharangeal cancers, [14] so the potential for benefit is significant.

In addition, with the reduced rates of smoking, HPV is becoming an increasingly significant cause of oropharyngeal cancer. [32] Most of the oropharyngeal cancers in non-smokers are caused by HPV infections, and the majority of patients are men. [32] Vaccinating women alone is less effective in reducing the rates of infection and both males and females need to be vaccinated for maximal benefit. [22] Male HPV vaccination is expected to lead to a reduction in the oncogenic HPV prevalence in the community and together with female HPV vaccination, it may reduce the incidence of HPV related oropharyngeal cancers in non-smokers. [32]

However, the lack of long term data means that it is uncertain how long immunity will last before a booster is necessary. Current followup studies suggest that the vaccine remains effective in a population vaccinated 8.5 years ago. [8] Further follow-up is necessary to ensure that the vaccine continues to be effective over longer periods of time.

Populations at risk

There is poor uptake of the National Cervical Screening program among women of Aboriginal and Torres Strait Islander (ATSI) background. [7] Among other factors, this poor uptake is one of the reasons why they have twice the risk of developing cervical cancer and their mortality rate is 5 times higher than the general population. [7]

Including boys in the vaccination program has been modelled to further decrease the rates of genital warts and cervical cancer beyond that which would be attained by female vaccination alone. [30] However, the argument has been made that if there is sufficient uptake of vaccination among girls most males would eventually be protected through female vaccination alone. [22] This argument has merit if the vaccination rates among girls are extremely high, but it assumes transmission only through heterosexual relationships. One of the populations at highest risk of HPV infection is men who have sex with men (MSM). [5] This population acquires little benefit from the current HPV vaccination program, [5] and logic suggests that the HPV infections would persist in this population even with immunisation of all females. MSM are at 30 times the risk of anal cancer when compared with other men. [5] As 90% of anal cancers are associated with HPV, [6] the vaccine has the potential to provide significant benefits for this high risk population. However, it would be difficult on many levels to target the MSM population for immunisation. Targeted immunisation would need to reach MSM at an early stage of sexual activity, but at that time many may be reluctant to disclose their sexual orientation due to a fear of stigma. [5] Therefore, a program of routine male vaccination solves the need to target this group specifically by immunising all young boys prior to sexual debut.

Another population which is at higher risk of HPV infection is men and women with impaired immunity such as organ transplant recipients. [6] Although heterosexual males with impaired immunity may have some protection from the HPV vaccination program for girls, [5,30] heterosexual females and MSM with impaired immunity would not receive the same degree of protection. Immunosuppressed populations are more likely to develop persistent infections which progress to dysplasia and cancer. [6] Wide vaccine coverage would ensure high levels of immunity in the community that should lower the risk of HPV transmission to all high risk groups.

Cost effectiveness

The immediate costs of implementing and monitoring the female-only HPV program was reported in 2007 to be AU$103.5 million over five years. [33] The addition of males to the program added AU$21.1 million over four years in 2012. [12] Although the Australian Government has approved the addition of males to the HPV vaccination program, the cost effectiveness of such a move is still debated in Australia and worldwide. [5,14,34,35]

Some studies have reported that the vaccination of males is not cost effective when compared to female vaccination alone. [5,14,34,35] These reports were made with the commonly used consideration that an incremental cost-effectiveness ratio (ICER) of greater than US$50,000 per quality-adjusted life-year (QALY) is not considered costeffective. [5] However, other studies have shown that the equation becomes much more favourable when protection against all HPV related diseases affecting men and women are included, as that drops the ICER to US$25,664 per QALY. [36]

Although the Australian Government has not released their analysis on the cost effectiveness of including males in the HPV vaccination program, past experience suggests that anything below an ICER of less than AU$60,000 per QALY is generally accepted. [5]

The cost models can only provide an estimation of the impact of HPV not be apparent for some time. This is due to the time interval between HPV infection and the development of cancer. [3,36] However, the rates of genital warts, which are more prevalent and develop more quickly, are already decreasing. [25,26]

The cost per person of vaccination may seem high initially but when the cumulative effects of herd immunity are taken in to account the equation becomes more favourable. [24] In addition, the benefits of HPV vaccination are many, and cost effectiveness studies should take into account the psychosocial benefit, the reduction in the clinical burden of disease, as well as the reduced costs of treating the various presentations of HPV related cancers and genital warts. For example, the treatment of genital warts alone is estimated to cost AU$14 million annually in Australia. [27]

Future research and monitoring

Monitoring the efficacy, safety and the impact of HPV vaccination is an important step in measuring the effectiveness of the vaccination program and in guiding future policy. There are some challenges in vaccine program monitoring due to the long time interval between HPV infection and the development of HPV related cancers, as well as the asymptomatic and transient nature of infection. [3,37] However, the setup of the National HPV Vaccine Program Register (NHVPR) is a key step towards collecting vaccine coverage and dose status data of the target population, as well as collecting basic demographic data of recipients across Australia. [33] This information is only collected with prior consent and enables administrators to match accurate data collected from different registers to individuals. This allows them to run follow up programs to send reminders for missed doses or for boosters if they are required in the future. These data, combined with the information collected by state based cervical cytology registers and the Australasian Association of Cancer Registries provides a powerful tool to quantify the impact of the vaccination program on the incidence of cervical and other HPV related cancers in the long term.

Information regarding the safety of the vaccine and any associated adverse effects is collected by the Medicines Safety Monitoring office of the Therapeutic Goods Administration. [20] However, currently there are no nationally funded programs which monitor HPV genotypes in the general population and the vaccinated group. This could be a method to monitor HPV prevalence in the future or a way to screen for HPV related cancers. [7] The impact of vaccination on targeted groups such as MSM and ATSI Australians should also be monitored to evaluate the impact of the prophylactic vaccine on these high risk groups.

Summary

The aim of the Australian immunisation program is to introduce immunity against the included HPV types before the commencement of sexual activity through a prophylactic HPV vaccine. Through this program, males and females in the pre-adolescent age group are immunised before their sexual debut (which usually creates a peak in incidence of HPV). [38]

Although the use of barrier contraception such as condoms, and male circumcision may offer some protection, any skin-to-skin contact during sexual activity can result in the transmission of HPV. [3] Currently, HPV vaccination is the only reliable and realistic method of primary prevention of HPV infection. It has proven to be safe with a high efficacy and minimal side effects. [20,21] The vaccination has the potential to significantly reduce the clinical burden of HPV-related disease, the associated high costs of treatment, and the adverse psychological impact which can be caused by the diagnosis of a HPV related disease. [28,29]

Male vaccination not only provides benefits to its recipients but also provides indirect benefits to females and the wider population. This will result in accelerated herd immunity and increase the protection offered to susceptible and high risk groups such as unvaccinated females, MSM, immunocompromised individuals, and members of the ATSI community.

Furthermore, the introduction of HPV vaccination for all young males and females will further Australia’s contribution to the prevention of HPV associated diseases worldwide and provide invaluable data describing the long term effects of HPV vaccination. For a population based primary prevention program to be successful there needs to be strict and persistent surveillance and monitoring of its implementation. Currently, Australia has no national program for the surveillance of HPV or genital warts, although it has setup the NHVPR, which monitors the population vaccination coverage. In collaboration with the PAP test and cancer registries, the information collected through this register should provide invaluable data on the impact of HPV vaccination in females. This monitoring will be extended in 2014 to include males, providing a robust data set enabling the measurement of the impact of HPV vaccination on the incidence of HPV related cancers in the coming years.

Conflict of interest

None declared.

Acknowledgements

We would like to thank Dr. Richard Mayes and Dr. Catherine Foley for their assistance and support.

Correspondence

M Boulat: mbou13@student.monash.edu
A Hatwal: ahat5@student.monash.edu

References

[1] Gottschling M, Goker M, Stamatakis A, Bininda-Emonds ORP, Nindl I, Bravo IG. Quantifying the phylodynamic forces driving papillomavirus evolution. Molecular Biology & Evolution. 2011 July; 28(7): p. 2101-13.
[2] Trottier H, Burchell AN. Epidemiology of Mucosal Human Papillomavirus Infection and Associated Diseases. Public Health Genomics. 2009 August 11; 12(5): p. 291-307.
[3] Stanley M. Pathology and epidemiology of HPV infection in females. Gynecologic Oncology. 2010 January; 117(2): p. 5-10.
[4] Stevens MP, Garland SM, Tan JH, Quinn MA, Petersen RW, Tabrizi SN. HPV Genotype Prevalence in Women With Abnormal Pap Smears in Melbourne, Australia. Journal of Medical Virology. 2009 July; 81(7): p. 1283–1291.
[5] Georgousakis M, Jayasinghe S, Brotherton J, Gilroy N, Chiu C, Macartney K. Populationwide vaccination against human papillomavirus in adolescent boys: Australia as a case study. The Lancet Infectious Diseases. 2012 August; 12(8): p. 627-34.
[6] Barroso LF, Wilkin T. Human Papillomavirus Vaccination in Males: The State of the Science. Current Infectious Disease Reports. 2011 April; 13(2): p. 175-81.
[7] Australian Institute of Health and Welfare. Cervical screening in Australia 2009-2010. Canberra:, Australian Government Department of Health and Ageing; 2012.
[8] Immunise Australia Program. Fact Sheet: National Immunisation Program – HPV Vaccination for Boys. Canberra:, Australian Government Department of Health and Aging; 2012.
[9] M GS, Skinner SR, Brotherton JML. Adolescent and young adult HPV vaccination in Australia: Achievements and Challenges. Preventative Medicine. 2011 October; 53(1): p.29-35.
[10] The National HPV Vaccination Program. Protecting you daughter from cervical cancer. Immunise Australia Program; 2007 March.
[11] Kirby T. Australia to be first country to vaccinate boys against HPV. The Lancet. 2012 August; 13(8): p. 333.
[12] Plibersek T. Minister for Health. [Online]. Canberra; 2012 [cited 2012 10 30. Available from: http://www.health.gov.au/internet/ministers/publishing.nsf/Content/mr-yr12-tptp059.htm
[13] Koutsky L. The Epidemiology behind the HPV Vaccine Discovery. Annals of Epidemiology. 2009 April; 19(4): p. 239-44.
[14] Kim JJ, Goldie SJ. Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States. British Medical Journal. 2009 October; 339:b3884.
[15] de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology. 2012 June; 13(6): p. 607-615.
[16] Parkin M, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine. 2006 August; 24(3): p. 11-25.
[17] National HPV Vaccination Program Register. Immunise Australia Program. [Online].; 2011 [cited 2012 October 22. Available from: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/immunise-hpv
[18] Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, et al. Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males. The New England Journal of Medicine. 2011 February; 364(5): p. 401-11.
[19] Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. The Lancet. 2007 May; 369(9574): p. 1693-702.
[20] Therapeutic Goods Administration. Gardasil (human papillomavirus vaccine). [Online].; 2010 [cited 2012 October 12. Available from: http://www.tga.gov.au/safety/alerts-medicine-gardasil-070624.htm
[21] Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, et al. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006 November; 118(5): p. 2135-45.
[22] Garnett GP. Role of Herd Immunity in Determining the Effect of Vaccines against Sexually Transmitted Disease. The Journal of Infectious Diseases. 2005 February; 191(1): p. 97-106.
[23] Song N, Gao Z, Wood JG, Hueston L, Gilbert GL, MacIntyre CR, et al. Current epidemiology of rubella and congenital rubella syndrome in Australia: Progress towards elimination. Vaccine. 2012 May; 30(27): p. 4073-8.
[24] Clemens J, Shin S, Ali M. New approaches to the assessment of vaccine herd protection in clinical trials. the lancet infectious diseases. 2011 June; 11(6): p. 482-7.
[25] Donovan B, Franklin N, Guy R, Grulich AE, Regan DG, Ali H, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. The Lancet Infectious Diseases. 2011 January; 11(1): p. 39-44.
[26] Read TR, Hocking JS, Chen MY, Donovan B, Bradshaw CS, Fairley CK. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sexually Transmitted Infections. 2011 December; 87(7): p. 544-7.
[27] Pirotta M, Stein AN, Conway EL, Harrison C, Britt H, Garland S. Genital warts incidence and healthcare resource utilisation in Australia. Sexually Transmitted Infections. 2010 June; 86(3): p. 181-6.
[28] Pirotta M, Ung L, Stein A, Conway EL, Mast TC, Fairley CK, et al. The psychosocial burden of human papillomavirus related disease and screening interventions. Sexually Transmitted Infections. 2009 December; 85(7): p. 508-13.
[29] Woodhall S, Ramsey T, Cai C, Crouch S, Jit M, Birks Y, et al. Estimation of the impact of genital warts on health-related quality of life. Sexually Transmitted Infections. 2008 June; 84(3): p. 161-6.
[30] Garland SM. Prevention strategies against human papillomavirus in males. Gynecologic Oncology. 2010 May; 117(2): p. 20-5.
[31] Miralles-Guri C, Bruni L, Cubilla AL, Castellsagué X, Bosch FX, de Sanjosé S. Human papillomavirus prevalence and type distribution in penile carcinoma. Journal of Clinical Pathology. 2009 October; 62(10): p. 870-8.
[32] Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007 October; 110(7): p. 1429-35.
[33] Abbott T. National Health Amendment (National HPV Vaccination Program Register) Bill 2007. Canberra: The Parliament of the Commonwealth of Australia, House of Representatives; 2007.
[34] Taira AV, Neukermans CP, Sanders GD. Evaluating human papillomavirus vaccination programs. Emerging Infectious Diseases. 2004 November; 10(11): p. 1915-23.
[35] Jit M, H CY, J EW. Economic evaluation of human papillomavirus vaccination in the United Kingdom. British Medical Journal. 2008 July; 337:a769.
[36] Elbasha EH, Dasbach EJ. Impact of vaccinating boys and men against HPV in the United States. Vaccine. 2010 October; 28(42): p. 6858-67.
[37] Brotherton JM, Kaldor JM, Garland SM. Monitoring the control of human papillomavirus (HPV) infection and related diseases in Australia: towards a national HPV surveillance strategy. Sexual Health. 2010 September; 7(3): p. 309-10.
[38] Gertig DM, Brotherton JM, M S. Measuring human papillomavirus (HPV) vaccination coverage and the role of the National HPV Vaccination Program Register, Australia. Sexual Health. 2011 June; 8(2): p. 171-8.
[39] de Villiers EM, Fauquet C, Broker TR, Bernard HU, Hausena Hz. Classification of papillomaviruses. Virology. 2004 June 20; 324(1): p. 17-27.