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Melioidosis in the Torres Strait Islands: an 11 year audit 2001-2012

Melioidosis is an infection of concern to global health. It is caused by the intracellular gram-negative bacterium Burkholderia pseudomallei, which is found in the soil and fresh waters of endemic regions. This study identified the average annual incidence of melioidosis in the Torres Strait region between 2001-2012, and compared this to one other similar study, which identified the average annual incidence between 1995-2000. Patient demographics, clinical presentation, outcomes and risk factors were compared to other available studies. In this retrospective study of melioidosis in the Torres Strait, 31 cases were identified over an 11-year period, representing an annual incidence of 37 cases per 100,0000 population. Of these cases, 84% recovered, 16% required intensive care unit (ICU) admission, 3% had a relapse and two patient deaths occurred. The mortality rate was 6.4%. Pneumonia accounted for fifteen presentations (48%) and splenic abscesses for ten presentations (32%), with nine patients presenting with septic arthritis of a joint (29%). Other presentations included hepatic (19%), prostatic (19%), renal (10%), skin (6%), pancreatic (3%), scrotal (3%) and spinal abscesses (3%). Four presented with bacteraemia alone (13%) and one case presented with urethritis (3%). Risk factors included diabetes mellitus (68%), excessive alcohol intake (35%), renal disease (12%), autoimmune disease (6%), malignancy (4%) and the use of immunosuppressive medication (2%).

Introduction

Melioidosis is an infection caused by the intracellular gram-negative bacterium Burkholderia pseudomallei, which is found in the soil and fresh waters of endemic regions. [1] Endemic regions include Southeast Asia and Northern Australia, with peaks of infection occurring during the wet seasons. [2] Melioidosis is of global public health significance, and may be thought of as an emerging infection across tropical regions. [3]

The Torres Strait is a tropical region comprised of 274 islands between the Cape York Peninsula of mainland Australia and Papua New Guinea (PNG). According to the 2006 Australian Bureau of Statistics (ABS) census data, the region has a total population of 7,624, with 82.5% identifying as Indigenous. [4] Half of this population is clustered within the central island group located closest to Thursday Island (TI), which is the commercial and governmental centre of the region. Hospital services are also centralised at TI, however, the closest tertiary referral centre for the Torres Strait region is the Cairns Base Hospital, located 800km south of TI.

Melioidosis is endemic in the Torres Strait, with the most recent average annual incidence reported to be 42.7 cases per 100,000. [5] This is significantly greater than other centres such as Darwin, where the annual incidence was noted to be 19.6 cases per 100,000 between 1986 and 2008. [6] However, during periods of extreme climate, such as during years of significant heavy rainfall, this incidence dramatically increases. This was observed in Darwin between 2009 and 2010, during which the annual incidence increased to 50.2 cases per 100,000, as a result of a heavy wet season. [7] The variability in annual incidence highlights the significant relationship between the transmission of melioidosis and certain environmental factors, such as rainfall level. [1,2]

The transmission of melioidosis most commonly occurs through percutaneous inoculation, and less commonly through inhalation, aspiration and ingestion. [2] A range of host and environmental factors must also exist for an individual to be infected. This includes reduced host immunity and the significant environmental exposure to the pathogen which occurs in endemic regions. [1] This was demonstrated in the study by Kanaphun et al. conducted in northeast Thailand, in which serological studies of 80% of the population exhibited positivity for antibodies against B. pseudomallei by four years of age. [18] There is clear significant environmental exposure in populations of northeast Thailand, yet only 20% of these children developed a symptomatic infection. [1,18] In addition, of the adults infected with symptomatic melioidosis, over 80% displayed reduced host immunity, with most affected by diabetes mellitus or renal failure. [8] In comparison, studies conducted in Australia demonstrated that most individuals were affected by excessive alcohol consumption and diabetes mellitus. [9]

The clinical syndrome associated with the infection of B. pseudomallei is diverse and can affect a variety of organs. Both domestic and international literature overwhelmingly demonstrated the lung as the most commonly affected organ, with pneumonia being the most common clinical presentation of melioidosis. [7,9] Other clinical presentations include symptoms of septicaemia such as fever, malaise, pain in the joints or abdomen, which may be the result of abscess formation in the liver, prostate, kidney, skin or pancreas.

The incubation period varies, as B. pseudomallei can remain dormant for a prolonged period of time. This makes it difficult to establish the exact period of infection. In most cases, a diagnosis of melioidosis is made through positive cultures demonstrating the growth of B. pseudomallei. Serological evidence can also be used to demonstrate past infections, or the presence of rising titres can provide a diagnosis in the absence of positive cultures. [2]

Recurrence of melioidosis can occur in 15% of individuals within ten years of the primary infection, with 50% of these occurring within the first twelve months. [10] Overall, 25% of individuals with recurrence will die. [10] Risk factors for recurrence include severity of initial infection, treatment regime and compliance, and short treatment duration. [10]

Within Australia, it was noted that the mortality rate was similar across the Torres Strait, North Queensland and Darwin. The most recent study conducted in the Torres Strait demonstrated a 22% mortality rate, [5] whilst a larger study in Darwin exhibited a similar mortality rate of 19%. [6,9]

The literature demonstrates the importance of melioidosis to the Torres Strait region. Its seasonal, wet, tropical location and its burden of chronic disease make it a prime location for B. pseudomallei. Furthermore, the most recent examination of this condition in the area is ten years old, highlighting the need for more recent data. This study aims to retrospectively examine all melioidosis cases between the year 2001 and 2012, in order to understand the current burden, risk factors and disease pattern of melioidosis in the Torres Strait.

Methods

This study aimed to conduct a retrospective audit of all patient data between 2001 and 2012, with diagnosis of melioidosis confirmed by isolation of B. pseudomallei. Patients who had been coded as having a diagnosis of a melioidosis infection within this period were identified. All patients who had a positive culture or serology for melioidosis were identified through Queensland Health Pathology. Electronic records were accessed for confirmation of diagnosis and to collect patient medical history, social history and medication lists. Electronic data was accessed through the Queensland Health Electronic Discharge Summary (EDS) program and via clinical notes in Best Practice. AusCare was accessed to confirm positive blood or swab cultures.

Positive serological diagnoses without supporting positive cultures were excluded. Patients with negative pus or blood cultures were excluded. Patient records were de-identified and analysed for demographical data, risk factors, clinical presentation and outcomes. All cases identified were acquired within the Torres Strait region.

Patient transfer to a tertiary hospital for further management and treatment did not result in exclusion of the patient. Once stabilisation was achieved in tertiary centres, patients returned to the TI Hospital to complete treatment, and were not listed as an additional case in the study.

Annual incidence rates were calculated using the 2006 ABS population census data of the Torres Strait region. [4] Recognised risk factors for melioidosis were utilised to aid in analysis of patient records. Data were compared to previous studies from both the Torres Strait and other similar regions within Australia, to determine similarities and differences across these areas.

Patient occupational data was not included in this study, as they were not reflective of environments which would cause significant increased exposure to B. pseudomallei.

Results

Melioidosis was confirmed in 31 cases by isolation of B. pseudomallei from any clinical sample. Of the 31 cases, 28 cases were confirmed by blood culture and two cases were confirmed by swab culture of pus, one from a septic ankle and the other from an epidural abscess. These two cases did not culture B. pseudomallei in serological samples. This represented an average annual incidence of 37 cases per 100,000 of melioidosis within the Torres Strait region.

The majority of individuals affected were male (65%), of Torres Strait Islander decent (Figure 1), with a median age of distribution between 40-49 years (Figure 2). Most patients presented from outer islands (71%), in particular Badu Island. Ninety percent of presentations occurred during the wet season months of the Torres Strait, between January and May.

Many patients had more than one risk factor, and diabetes mellitus was by far the most common, present in 21 cases (68%). Excess ethanol intake (35%) and renal disease (12%) were also identified as significant risk factors in this study. Autoimmune disease (6%), malignancy (4%) and the use of immunosuppressive medication (2%) were considered minor risk factors (Figure 3). Significant risk factors were defined as those that represented a higher percentage in the population as extrapolated from data. Obesity, heart disease and COPD were not identified as significant risk factors in this study.

Of all cases, pneumonia was the most common presentation (48%), closely followed by splenic abscesses (32%) and septic arthritis of a joint (29%). Other presentations included hepatic (19%), prostatic (19%), renal (10%), skin (6%), pancreatic (3%), scrotal (3%) and spinal abscesses (3%). Four presented with bacteraemia alone (13%), and one case presented with urethritis (3%) (Figure 4).The majority of patients (84%) recovered with a total of five ICU admissions (16%), two patients had long- term disability and there were two deaths, giving a mortality rate of 6.4%. Two of the 31 cases occurred in children, one in a five-week old infant with the outcome of death, and one in a five year old child who was not of Aboriginal or Torres Strait Islander origin, who presented with pneumonia and septicaemia. One case of relapse was identified in a 30-year old male from Badu Island who was non-adherent with treatment following discharge from ICU at the Cairns Base Hospital.

Discussion

To date, this study is the largest retrospective study of melioidosis within the Torres Strait. It highlights that melioidosis continues to be a disease of significance in the region, despite a larger public profile in recent years. [3] The average annual incidence reported in this study is 37 cases per 100,000 between 2001 and 2012, less than that reported in a previous study examining 1995 to 2000, in which a total of 24 cases were reported, giving an annual incidence of 42.7 cases per 100,000. [5] The incidence of melioidosis in the Torres Strait remains one of the highest in Australia, excluding the seasonal peak in Darwin between 2009 and 2010. [6] The finding of this study is high compared to international figures, such as those reported in Thailand, where the annual incidence of melioidosis is 5.5 per 100,000. [10]

The high incidence reported here could be attributed to a number of environmental and population factors unique to the Torres Strait region. Climate is a major factor, as the Torres Strait region has very high rainfall during the seasonal wet months from December to May. [5] This reinforces the seasonal distribution of melioidosis, as 90% percent of cases identified occurred within these months. This strong association between the incidence of melioidosis and the rainfall patterns highlights an opportunity for public health intervention to be focussed on the annual wet period in the Torres Strait. In addition, melioidosis incidence was highest on TI (26%), closely followed by Badu Island (23%), which creates additional target locations for public health intervention.

In alignment with the literature, our study demonstrated an over-representation of the Indigenous population presenting with melioidosis. Out of the 31 cases, 28 identified as Indigenous (93.5%), and only three as non-Indigenous. This could be attributed to the generally poorer health status of Indigenous Australians, and the higher rates of chronic illness such as diabetes mellitus, resulting in this population being more susceptible to melioidosis infection. [11] The higher incidence of melioidosis may also be attributed to the cultural differences in the Indigenous population of the Torres Strait. This population has been anecdotally noted to rarely wear shoes, and to spend much of their time in outdoor activities such as fishing. This results in a significant higher environmental exposure to B. pseudomallei.

The incidence of diabetes mellitus within the Torres Strait is one of the highest in Australia, with one third of the population affected. [11] Diabetes mellitus is considered to be one of the most significant risk factors for melioidosis infection, both in Australia and abroad. [10] This was confirmed in this study, with 68% of the case patients identified as having type 2 diabetes mellitus. In comparison to studies in Thailand and Malaysia, 60.3% and 70.4% of their case participants, respectively, were identified as having diabetes mellitus. [12,13] Alternatively, in Darwin, a 20-year prospective melioidosis study from 1989 to 2009, which included 540 cases, identified 39% with underlying type 2 diabetes mellitus. [3] Similarly, a 10-year prospective study in northern Australia identified 37% with diabetes mellitus. [4] Other important risk factors for melioidosis identified were excessive alcohol use (35%) and renal disease (12%). These have been previously identified however alcohol use was considered to be a more significant risk factor for melioidosis in Australia, and renal disease a more significant risk factor in South East Asia. [7,10]

Melioidosis presentation in this study commonly included pneumonia, septic arthritis, and hepatic, splenic and prostatic abscesses. Of these, pneumonia was the most common form of presentation (48%), which reinforces aerosol inoculation as an important transmission route. This finding was similar to that found in numerous studies [3,4]; however, genitourinary infections (3%) were not as common in our study. Genitourinary infections represented 15% of presentations in studies conducted in northern Australia [4] and 14% of presentations in studies conducted in Darwin. [3] Further differences existed in cases presenting with bacteraemia. In our study, 13% of cases presented with bacteraemia alone, compared with 46% of cases presenting with bacteraemia in a north Australian 10-year study. [3] The mortality rate in our study was 6.4%, which was also lower than the north Australian study which reported a mortality rate of 19%. [3] International mortality rates are significantly higher than in Australia, and were reported to be 63% in a Malaysian study and 49% in a Thailand study. [10]

For future follow up and extension of this study, another similar audit would be beneficial to complete for 2012-2022. A future audit would create continuity of data, and would provide further analysis of melioid disease patterns. Melioid disease patterns may be observed to decrease in incidence as a result of increased public awareness, improved access to health care and improved infrastructure, as most of the outer islands currently consist of unpaved roads. Alternatively, the suggested effects of climate change on weather patterns and increased rainfall could lead to an increase in melioidosis incidence, due to the strong environmental links. [1,15-17]

Another type of study that would be beneficial for the Torres Strait region would be to investigate the levels of B. pseudomallei exposure patterns. This would involve environmental sampling, to determine the concentration of B. pseudomallei present in the soils, waters and grasses across different islands. [14] This data could then be cross-referenced with our study data, which identified specific islands as having a higher number of clinical cases. Environmental studies could provide and explanation for the higher incidence of melioidosis present on particular Torres Strait islands. For example, if a decreased concentration of B. pseudomallei was found in the soils, waters and grasses of Badu Island, the health status of the population may be considered as a more weighted risk factor for melioidosis relative to environmental exposure.

Finally, a cost analysis study of the financial burden of melioidosis could be completed. Our study identified that the majority of patients required long stay admissions at TI Hospital and tertiary centres, and that a significant proportion of cases (16%) required ICU stay. This financial burden of melioidosis on the public health system needs to be addressed, as it may provide further incentive to fund greater public health programs aimed at the primary prevention of melioidosis.

Acknowledgements

We acknowledge and appreciate the support and input from all the staff at the TI Hospital. We would like to particularly thank medical records and the pathology department at TI Hospital.

Conflict of interest

None declared.

Correspondence

K Rac: kathrinrac@gmail.com

[1] Wiersinga WJ, van der Poll T, White NJ, Day NP, Peacock SJ. Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei.  Nature Review: Microbiology 2006;4:272-282.

[2] Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. The New England Journal of Medicine 2012; 367: 1035-1044.

[3] Dance DAB. Meliodosis as an emerging global problem.  Acta Tropica 2000;74:115-119.

[4] Australian Bureau of Statistics. National regional profile: Torres Strait Islands [Internet]. 2007 [cited 2012 April 24]. Available from:  http://www.censusdata.abs.gov.au

[5] Faa AG, Holt PJ. Melioidosis in the Torres Strait Islands of far North Queensland. Communicable Diseases Intelligence 2002;26:279-283.

[6] Parameswaran U, Baird RW, Ward LM, Currie BJ. Melioidosis at Royal Darwin Hospital in the big 2009-2010 wet season: comparison with the preceding 20 years.  Medical Journal Australia 2012; 196(5):345-8.

[7] Currie BJ, Fisher DA, Howard DM, Burrow JN, Selvanayagam S, Snelling PL, Anstey NM, Mayo MJ. The epidemiology of melioidosis in Australia and Papua New Guinea” Acta Tropica 2000;74:121-127.

[8] Malczewski AB, Oman KM, Norton RE, Ketheesan N. Clinical presentation of Melioidosis in Queensland, Australia. Royal Society of Tropical Medicine and Hygiene 2005; 99(11):856-60.

[9] Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, Anstey NM, Huffam SE, Snelling PL, Marks PJ, Stephens DP, Lum GD, Jacups SP, Krause VL. Endemic Melioidosis in tropical northern Australia: a 10 year prospective study and review of the literature.  Clinical Infectious Diseases 2000; 31:981-6.

[10] Limmathurotsakul D, Chaowagul W, Chierakul W, Stepniewska K, Maharjan B, Wuthiekanun V, Day NP, Peacock SJ. Risk Factors for Recurrent Melioidosis in Northeast Thailand. Clinical Infectious Disease 2006; 43:979-986.

[11] McDermott RA, McCulloch BG, Campbell SK, Young DM. Diabetes in the Torres Strait of Australia: Better clinical systems but significant increase in weight and other risk conditions among adults, 1999-2005. Medical Journal of Australia 2007; 186:505-508.

[12] Leelarasamee A. Meliodosis in Southeast Asia. Acta Tropica 2000; 74:129-132.

[13] Hansan DZ, Suraiya S. Clinical characteristics and outcomes of bacteraemic melioidosis in a teaching hospital in a north-eastern state of Malaysia: a five year review. Journal of Infections in Developing Countries 2010; 4(4):430-435.

[14] Currie BJ, Ward L, Cheng AC. The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. Neglected Tropical Diseases 2010; 30:4-11.

[15] Suppiah R, Collier MA, Kent D. Climate change projections for the Torres Strait region [Internet] 2011. [Cited 2012 April 14]. Available from: http://www.mssanz.org.au/modsim2011/F5/suppiah.pdf

[16] Costello A, Abbas M, Allen A, Ball S, Bellamy R, Friel S, Groce N, Johnson A, Kett M, Lee M, Levy C, Maslin M, McCoy D, McGuire B, Montgomery H, Napier D, Pagel C, Patel J, de Oliveira JA, Redclift N, Rees H, Rogger D, Scott J, Stephenson J, Twigg J, Wolff J, Patterson C. Managing the health effects of climate change. The Lancet 2009; 373:1693-1733.

[17] Kaestli M, Schmid M, Mayo M, Rothballer M, Harrington G, Richardson L, Hill A, Hill J, Tuanyok A, Keim P, Hartmann A, Currie BJ. Out of the ground: aerial and exotic habitats of melioidosis bacterium Burkholderia pseudomallei in grasses in Australia. Environmental Microbiology 2012; 14(8):2058-70

[18] Kanaphun P, Thirawattanasuk N, Suputtamongkol Y, Naigowit P, Dance ABD, Smith MD, White NJ. Serology and Carriage of Pseudomonas pseudomallei: A prospective Study in 1000 Hospitalized Children in Northeast Thailand.  Journal of Infectious Diseases 1993; 167(1): 230-233.
Social phobia in children – risk and resilience factors

Categories
Letters Articles

Lessons learned from internship

Many medical students this year have asked me about what it is like to become an intern. The truth is, nothing you learn at medical school can fully prepare you for the transition to internship. In fact, 42% of newly qualified doctors feel their medical training does not adequately prepare them for starting work. [1] However, it’s not all drama and chaos as shows like House would make you believe. Most internship work is spent on paperwork, requesting investigations and simple procedures like inserting cannulas and taking bloods.

From day one, interns are often rostered for after-hours work, something medical students often have very little exposure to. All of a sudden, new interns may find themselves looking after several wards overnight. Even though some, like me, are interested in critical care medicine, it can still be a challenging thought that over a hundred patients’ lives are entrusted to your care. My first after-hours shift will always stick in my mind, having given me many valuable lessons that I have taken through internship. This is that night in my life:

It is 5pm and most of the doctors have already left. I turn on my pager, secretly hoping it will not beep. Two minutes into the shift, the pager sounds and anxiety kicks in. The nurse on the other side of the phone requests, “Doctor, can you please dose this patient’s warfarin?” It feels strange to not have any other doctors nearby, and my first thought is to ‘phone a friend’. However, I hold off, remembering that the answer lies in the hospital protocol for warfarin, found on all the computers. It reminds me that there is always an abundance of resources and guidance available to us as medical students and interns – if we are willing to ask and look for them.

For the next hour, the tasks are manageable. I re-chart medication charts and get a request to insert a cannula into an elderly lady for intravenous fluids. The team struggled to put the last one in, and her newest one has fallen out during a shower. The lady is thin with fragile veins, and after three painful attempts, the cannula still isn’t in. She is tired of being poked and prodded, and I’m feeling frustrated. I decide to take a break and come back later.

The nurses then page urgently for a doctor. A patient has slipped and knocked his head, and now lies on the floor with a pool of blood beside him. When I arrive at the ward, I find a nurse beside the patient saying, “Everything’s going to be OK, the doctor’s here now,” as if a miracle is about to happen. I do not feel like anyone’s miracle worker, but as one of the first responders and because more senior help had not arrived yet, the nurses look to me for further instructions. My mind freezes, but kickstarts to life again when the basics of ‘ABC’ spring to mind. I feel incredibly grateful for the medical school hammering the ABC approach for such situations. I begin to assess and treat the patient. His airway is patent, cervical spine protected, breathing and circulation maintained. We apply pressure to the wound and perform an ECG and glucose. The few minutes waiting for help to arrive seem to last forever. When more help arrives, we give a huge sigh of relief. I notice that all this time, the patient’s wife has been waiting outside and has been growing extremely worried. As the appropriate members are treating the patient, I take the opportunity to go to her, explain what is happening, and reassure her that her husband is being cared for. One of my consultants once told me that as a junior doctor, one of the best things to do in such situations is to communicate with the patient’s family.

Just when I think that there has been all the excitement I’d need in one night, the pager beeps again. A patient is spiking a high fever, and the nurse is requesting antibiotics. I check through the patients notes first and note that she has been spiking fevers in the last few days, cultures are negative, and the treating team thinks it may be viral. A septic screen has been done, and it was previously decided paracetamol should be sufficient  I reassess her and decide that she does not look too ill at this stage. She has been stable over the last few days.  I choose to leave her without antibiotics, as it does not seem likely that they will be beneficial. The next day, I will check on the patient and be relieved to see that the treating team did not decide to prescribe any antibiotics either.

Before the end of the shift, I go back to visit the elderly lady who still needs a cannula. If I fail, I’ll need to call the duty anaesthetist, and I feel bad because it is getting pretty late in the night. I discuss with the patient, and she agrees for me to have one last opportunity to try. I aim for a small vein in her left hand, and by some stroke of luck, the cannula goes in and flushes smoothly. I breathe a sigh of relief and thankfulness. It reinforces to me that sometimes, just when we are feeling down and tired from trying, we can come back to the task and succeed.

Every day in the hospital, you learn something new. After completing my internship, I am able to reflect back on how much I have learnt in the past year. Completing medical school makes you a doctor, but that is far from the end of the journey. If I may offer some advice, it would be to stay calm in unfamiliar situations, stick with what you have been taught, and never be afraid to ask for help.

Conflict of interest

None declared.

References

[1] Cave J, Woolf K, Jones A, Dacre J. Easing the transition from student to doctor: how can medical schools help prepare their graduates for starting work? Med Teach. 2009 May;31(5):403-8.

Categories
Review Articles Articles

Paediatric regional anaesthesia: comparing caudal anaesthesia and ilioinguinal block for paediatric inguinal herniotomy

Caudal anaesthesia and ilioinguinal block are effective, safe anaesthetic techniques for paediatric inguinal herniotomy. This review article aims to educate medical students about these techniques by examining their safety and efficacy in paediatric surgery, as well as discussing the relevant anatomy and pharmacology. The roles of general anaesthesia in combination with regional anaesthesia, and that of awake regional anaesthesia, are discussed, as is the administration of caudal adjuvants and concomitant intravenous opioid analgesia.

Introduction

Inguinal hernia is a common paediatric condition, occurring in approximately 2% of infant males, of slightly reduced incidence in females, [1] and as high as 9-11% in premature infants. [2] Inguinal herniotomy, the reparative operation, is most commonly performed under general anaesthesia with regional anaesthesia; however, some experts in caudal anaesthesia perform the procedure with awake regional anaesthesia. Regional anaesthesia can be provided via the epidural (usually caudal) or spinal routes, or by blocking peripheral nerves with local anaesthetic agents. The relevant techniques and anatomy will be discussed, as will side effects and safety considerations, and the pharmacology of the most commonly used local anaesthetics. The role of general anaesthesia, awake regional anaesthesia and the use of adjuvants in regional anaesthesia will be discussed, with particular focus on future developments in these fields.

Anatomy and technique

The surgical field for inguinal herniotomy is supplied by the ilioinguinal and iliohypogastric nerves, arising from the first lumbar spinal root, as well as by the lower intercostal nerves, arising from T11 and T12. [3] Caudal anaesthesia is provided by placing local anaesthetic agents into the epidural space, via the caudal route. It then diffuses across the dura to anaesthetise the ventral rami, which supply sensory (and motor) nerves. Thus, the level of anaesthesia needs to reach the lower thoracic region to be effective. The caudal block is usually commenced after the induction of general anaesthesia. With the patient lying in the left lateral position, the thumb and middle finger of the anaesthetist’s left hand are placed on the two posterior superior iliac spines, the index finger then palpates the spinous process of the S4 vertebra. [4] Using sterile technique, a needle is inserted through the sacral hiatus to pierce the sacrococcygeal ligament, which is continuous with the ligamentum flavum (Figure 1). Correct placement of the needle can be confirmed by the “feel” of the needle passing through the ligament, the ease of injection and, if used, the ease of passing a catheter through the needle. The absence of spontaneous reflux, or aspiration, of cerebrospinal fluid or blood should be confirmed before drugs are injected into the sacral canal, which is continuous with the lumbar epidural space. [5] Ilioinguinal block is achieved by using sterile technique to insert a needle inferomedially to the anterior superior iliac spine and injecting local anaesthetic between the external oblique and internal oblique muscles, and between the internal oblique and the transversus abdominis. [6] These injections cover the ilioinguinal, iliohypogastric and lower intercostal nerves, anaesthetising the operating field, including the inguinal sac. [3] Commonly, these nerves are blocked by the surgeon during the surgical process when she/he can apply local anaesthesia directly to the nerves. Ultrasound guidance has enabled the more accurate placement of injections, allowing lower doses to be used [7] and improving success rates, [8] leading somewhat to a resurgence of the technique. [4] Pharmacological aspects Considerable discussion has arisen regarding which local anaesthetic agent is the best choice for caudal anaesthesia: bupivacaine or the newer pure left-isomers levobupivacaine and ropivacaine. A review by Casati and Putzu examined evidence regarding the toxicology and potency of these new agents in both animal and human studies. Despite conflicting results in the literature, this review ultimately suggests that there was a very small difference in potency between the agents: bupivacaine is slightly more potent than levobupivacaine, which is slightly more potent than ropivacaine. [9] Breschan et al. suggested that a caudal dose of 1 mL/kg of 0.2% levobupivacaine or ropivacaine produced less post-operative motor blockade than 1 mL/kg 0.2% bupivacaine. [10] This result could be consistent with a mild underdosing of the former two agents in light of their lesser potency, rather than intrinsic differences in motor effect. Doses for ilioinguinal nerve block are variable, given the blind technique commonly employed and the need to obtain adequate analgesia. Despite this, the maximum recommended single shot dose is the same for all three agents: neonates should not exceed 2 mg/kg, and children should not exceed 2.5 mg/kg. [11] Despite multiple studies showing minimal yet statistically significant differences, all three agents are nonetheless comparably effective local anaesthetic agents. [9]

When examining toxicity of the three agents discussed above, Casati and Putzu reported that the newer agents (ropivacaine and levobupivacaine) were less toxic than bupivacaine, resulting in higher plasma concentrations before the occurrence of signs of CNS toxicity, and with less cardiovascular toxicity occurring at levels that induce CNS toxicity. [9] Bozkurt et al. determined that a caudal dose of 0.5 mL/kg of 0.25% (effectively 1.25 mg/kg) bupivacaine or ropivacaine resulted in peak plasma concentrations of 46.8 ± 17.1 ng/mL and 61.2 ± 8.2 ng/mL, respectively. These are well below the levels at which toxic effects appear for bupivacaine and ropivacaine, at 250 ng/mL and 150-600 ng/mL, respectively. [12] The larger doses required for epidural anaesthesia and peripheral nerve blocks carry the increased risk of systemic toxicity, so the lesser toxic potential of levobupivacaine and ropivacaine justifies their use over bupivacaine. [9,13] However, partly due to cost bupivacaine remains in wide use today. [14]

Caudal anaesthesia requires consideration of two aspects of dose: concentration and volume. The volume of the injection controls the level to which anaesthesia occurs, as described by Armitage:

  • 0.5 mL/kg will cover sacral dermatomes, suitable for circumcision
  • 0.75mL/kg will cover inguinal dermatomes, suitable for inguinal herniotomy
  • 1 mL/kg will cover up to T10, suitable for orchidopexy or umbilical herniotomy
  • 1.25 mL/kg will cover up to mid-thoracic dermatomes. [15]

It is important to ensure both an adequate amount of local anaesthetic (mg/kg) and an adequate volume for injection (mL/kg) are used.

Efficacy of caudal and ilioinguinal blocks

Ilioinguinal block and caudal anaesthesia both provide excellent analgesia in the intraoperative and postoperative phases. Some authors suggest that ultrasound guidance in ilioinguinal block can increase accuracy of needle placement, allowing a smaller dose of local anaesthetic. [16] Thong et al. reviewed 82 cases of ilioinguinal block without ultrasonography, and found similar success rates to other regional techniques, [17] however, this was a small study. Markham et al. used cardiovascular response as a surrogate marker for intraoperative pain and found no difference between the two techniques. [18] Other studies have shown that both techniques provide similarly effective analgesic profiles in terms of post-operative pain scores, [19] duration or quality of post-operative analgesia, [20] and post-operative morphine requirements. [21] Caudal anaesthesia has a success rate of up to 96%, [22] albeit with 25% of patients requiring more than one attempt. In contrast, blind ilioinguinal block has a success rate of approximately 72%. [23] Willschke et al. quoted success rates of 70-80%, which improved with ultrasound guidance. [16] In a small study combining the two techniques, Jagannathan et al. explored the role of ultrasound-guided ilioinguinal block after inguinal herniotomy surgery performed under general anaesthetic with caudal block. With groups randomised to receive injections of normal saline, or bupivacaine with adrenaline, they found that the addition of a guided nerve block at the end of the surgery significantly decreased post-operative pain scores for the bupivacaine with adrenaline group. [24] This suggests that the two techniques can be combined for post-operative analgesia. Ilioinguinal block is not suitable as the sole method of anaesthesia, as its success rate is highly variable and the block not sufficient for surgical anaesthesia, whereas caudal block can be used as an awake regional anaesthetic technique. Both techniques are suitable for analgesia in the paediatric inguinal herniotomy setting.

Complications and side effects

Complications of caudal anaesthesia are rare at 0.7 per 1000 cases. [5] However, some of these complications are serious and potentially fatal:

  • accidental dural puncture, leading to high spinal block
  • intravascular injection
  • infection and epidural abscess formation
  • epidural haematoma. [4,13]

A comprehensive review of 2,088 caudal anaesthesia cases identified 101 (4.8%) cases in which either the dura was punctured, significant bleeding occurred, or a blood vessel was penetrated. Upon detection of any of these complications, the procedure was ceased. [25] This is a relatively high incidence; however, these were situations where potentially serious complications were identified prior to damage being done by injecting the local anaesthetic. The actual risk of harm occurring is unknown, but is considered to be much lower than the incidence of these events. Polaner et al. reviewed 6011 single shot caudal blocks, and identified 172 (2.9%) adverse events, including eighteen positive test doses, five dural punctures, 38 vascular punctures, 71 abandoned blocks and 26 failed blocks. However, no serious complications were encountered as each of these adverse events were detected early and managed. [26] Methods of minimising the risk of these complications include test doses under ECG monitoring for inadvertent vascular injection (tachycardia will be seen) or monitoring the onset of subarachnoid injection (rapid anaesthesia will occur). [13] Ilioinguinal blocks, as with all peripheral nerve blocks, are inherently less risky than central blockade. Potential complications include:

  • infection and abscess formation
  • mechanical damage to the nerves.

More serious complications identified at case-report level include cases of:

  • retroperitoneal haematoma. [27]
  • small bowel perforation. [28]
  • large bowel perforation. [29]

Polaner et al. reviewed 737 ilioinguinal-iliohypogastric blocks, and found one adverse event (positive blood aspiration). [26] This low morbidity rate was attributed to the widespread use of ultrasound guidance. [26] A number of studies have examined the side effect profiles of both techniques:

  • Time to first micturition has conflicting evidence – Markham et al. suggest delayed first micturition with caudal anaesthesia
  • compared to inguinal block, [18] but others found no difference. [19,20]
  • Post-operative time to ambulation is similar. [18,19]
  • Post-operative vomiting has similar incidence, [18-20] and has been shown to be affected more by the accompanying method of general anaesthetic than the type of regional anaesthesia, with sevoflurane inhalation resulting in more post-operative vomiting than intravenous ketamine and propofol. [30]
  • Time in recovery bay post-herniotomy was 45 ± 15 minutes for caudal, and 40 ± 9 minutes (p<0.02) for ilioinguinal; [19] however, this statistically significant result has little effect on clinical practice.
  • Time to discharge (day surgery) was 176 ± 33 minutes for caudal block, and shorter for ilioinguinal block at 166 ± 26 minutes (p<0.02). [19] Again, these times are so similar as to have little practical effect. These studies suggest that the techniques have similar side effect incidences and postoperative recovery profiles, and where differences exist, they are statistically but not clinically significant.

Use of general anaesthesia in combination with caudal anaesthesia or ilioinguinal block A topic of special interest is whether awake regional, rather than general, anaesthesia should be used. Although the great majority of inguinal herniotomy is performed with general and regional anaesthesia, the increased risk of post-operative apnoea in neonates after general anaesthesia (particularly in ex-low birth weight and preterm neonates) is often cited. Awake regional anaesthesia is therefore touted as a safer alternative. As described above, ilioinguinal block is unsuitable for use as an awake technique, but awake caudal anaesthesia has been successfully described and practised. Geze et al. reported on performing awake caudal anaesthesia in low birth weight neonates and found that the technique was safe; [31] however, this study examined only fifteen cases and conclusions regarding safety drawn from such a small study are therefore limited. Other work in the area has also been limited by cohort size. [32-35] Lacrosse et al. noted the theoretical benefits of awake caudal anaesthesia for postoperative apnoea, but recognised that additional sedation is often necessary, and in a study of 98 patients, found that caudal block with light general anaesthesia using sevoflurane was comparable in terms of safety to caudal anaesthesia alone, and had the benefit of offering better surgical conditions. [36] Additionally, the ongoing concerns around neurotoxicity of general anaesthetic agents to the developing brain need further evaluation before recommendations can be made. [37] More research is needed to fully explore the role and safety of awake caudal anaesthesia, [38] and it currently remains a highly specialised area of practice, limited mainly to high risk infants. [39]

Adjuncts to local anaesthetics

There are many potential adjuncts for caudal anaesthesia, but ongoing concerns about their safety continue to limit their use. The effect of systemic opioid administration on the quality of caudal anaesthesia has been discussed in the literature. Somri et al. studied the administration of general anaesthesia and caudal block both with and without intravenous fentanyl, and measured plasma adrenaline and noradrenaline at induction, end of surgery and in recovery as a surrogate marker for pain and stress. They found adding intravenous fentanyl resulted in no differences in plasma noradrenaline, and significantly less plasma adrenaline only in recovery. [40] Somri et al. questioned the practical significance of the result for adrenaline, noting no clinical difference in terms of blood pressure, heart rate or end-tidal CO2. Thus they suggested that general anaesthesia and caudal anaesthesia adequately block the stress response, and therefore there is no need for intraoperative fentanyl. [40] Interestingly, they also found no difference in post-operative analgesia requirements between the two groups. [40] Other authors noticed no difference in analgesia for caudal anaesthesia with or without intravenous fentanyl, and found a significant increase in post-operative nausea and vomiting with fentanyl. [41] Khosravi et al. found that pre-induction tramadol and general anaesthesia are slightly superior to general anaesthesia and ilioinguinal block for herniotomy post-operative pain relief, but suggested that the increased risk of nausea and vomiting outweighed the potential benefits. [42] Opioids have a limited role in caudal injection due to side effects, including respiratory depression, nausea, vomiting and urinary retention. [43] Both ilioinguinal block and caudal block are effective on their own, and that the routine inclusion of systemic opioids for regional techniques in inguinal herniotomy is unnecessary and potentially harmful. Adding opioids to the caudal injection has risks that outweigh the potential benefits. [44]

Ketamine, particularly the S enantiomer which is more potent and has a lower incidence of agitation and hallucinations than racemic ketamine, [44] has been studied as an adjuvant for caudal anaesthesia. Mosseti et al. reviewed multiple studies and found ketamine to increase the efficacy of caudal anaesthesia when combined with local anaesthetic compared to local anaesthetic alone. [44] Similar results were found for clonidine. [44] This is consistent with other work comparing caudal ropivacaine with either clonidine or fentanyl as adjuvants, which found clonidine has a superior side effect profile. [45] However, the use of caudal adjuvants has been limited due to concerns with potential neurotoxicity (reviewed by Jöhr and Berger). [4]

Local anaesthetic with adrenaline has been used to decrease the systemic absorption of short acting local anaesthetics and thus enhance the duration of blockade. Its sympathetic nervous effects are also useful for identifying inadvertent intravascular injection, which results in increased heart rate and increased systolic blood pressure. The advent of longer acting local anaesthetics has led to a decline in the use of adrenaline as an adjuvant to local anaesthetics, [44] and the validity of test doses of adrenaline has been called into doubt. [46]

Summary and Conclusion

Both caudal and ilioinguinal blocks are effective, safe techniques for inguinal herniotomy (Table 1). With these techniques there is no need for routine intravenous opioid analgesia, thus reducing the incidence of problems from these drugs in the postoperative period. The role of ultrasound guidance will continue to evolve, bringing new levels of safety and efficacy to ilioinguinal blocks. Light general anaesthesia with regional blockade is considered the first choice, with awake regional anaesthesia for herniotomy considered to be a highly specialised field reserved for a select group of patients. However, the ongoing concerns of neurotoxicity to the developing infant brain may fundamentally alter the neonatal anaesthesia landscape in the future.

Conflict of interest

None declared.

Acknowledgements

Associate Professor Rob McDougall, Deputy Director Anaesthesia and Pain Management, Royal Children’s Hospital Melbourne, for providing the initial inspiration for this review.

Correspondence

R Paul: r.paul@student.unimelb.edu.au

References

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[2] Dalens B, Veyckemans F. Anesthésie pédiatrique. Montpellier: Sauramps Médical; 2006.
[3] Brown K. The application of basic science to practical paediatric anaesthesia. Update in Anaesthesia. 2000(11).
[4] Jöhr M, Berger TM. Caudal blocks. Paediatr Anaesth. 2012;22(1):44-50.
[5] Raux O, Dadure C, Carr J, Rochette A, Capdevila X. Paediatric caudal anaesthesia. Update in Anaesthesia. 2010;26:32-6.
[6] Kundra P, Sivashanmugam T, Ravishankar M. Effect of needle insertion site on ilioinguinaliliohypogastric nerve block in children. Acta Anaesthesiol Scand. 2006;50(5):622-6.
[7] Willschke H, Bosenberg A, Marhofer P, Johnston S, Kettner S, Eichenberger U, et al. Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: What is the optimal volume? Anesth Analg. 2006;102(6):1680-4.
[8] Willschke H, Marhofer P, Machata AM, Lönnqvist PA. Current trends in paediatric regional anaesthesia. Anaesthesia Supplement. 2010;65:97-104.
[9] Casati A, Putzu M. Bupivacaine, levobupivacaine and ropivacaine: are they clinically different? Best Pract Res, Clin Anaesthesiol. 2005;19(2):247-68.
[10] Breschan C, Jost R, Krumpholz R, Schaumberger F, Stettner H, Marhofer P, et al. A prospective study comparing the analgesic efficacy of levobupivacaine, ropivacaine and bupivacaine in pediatric patients undergoing caudal blockade. Paediatr Anaesth. 2005;15(4):301-6.
[11] Howard R, Carter B, Curry J, Morton N, Rivett K, Rose M, et al. Analgesia review. Paediatr Anaesth. 2008;18:64-78.
[12] Bozkurt P, Arslan I, Bakan M, Cansever MS. Free plasma levels of bupivacaine and ropivacaine when used for caudal block in children. Eur J Anaesthesiol. 2005;22(8):640-1.
[13] Patel D. Epidural analgesia for children. Contin Educ Anaesth Crit Care Pain. 2006;6(2):63-6.
[14] Menzies R, Congreve K, Herodes V, Berg S, Mason DG. A survey of pediatric caudal extradural anesthesia practice. Paediatr Anaesth. 2009;19(9):829-36.
[15] Armitage EN. Local anaesthetic techniques for prevention of postoperative pain. Br J Anaesth. 1986;58(7):790-800.
[16] Willschke H, Marhofer P, Bösenberg A, Johnston S, Wanzel O, Cox SG, et al. Ultrasonography for ilioinguinal/iliohypogastric nerve blocks in children. Br J Anaesth. 2005;95(2):226.
[17] Thong SY, Lim SL, Ng ASB. Retrospective review of ilioinguinal-iliohypogastric nerve block with general anesthesia for herniotomy in ex-premature neonates. Paediatr Anaesth. 2011;21(11):1109-13.
[18] Markham SJ, Tomlinson J, Hain WR. Ilioinguinal nerve block in children. A comparison with caudal block for intra and postoperative analgesia. Anaesthesia. 1986;41(11):1098-103.
[19] Splinter WM, Bass J, Komocar L. Regional anaesthesia for hernia repair in children: local vs caudal anaesthesia. Can J Anaesth. 1995;42(3):197-200.
[20] Cross GD, Barrett RF. Comparison of two regional techniques for postoperative
analgesia in children following herniotomy and orchidopexy. Anaesthesia. 1987;42(8):845-9.
[21] Scott AD, Phillips A, White JB, Stow PJ. Analgesia following inguinal herniotomy or orchidopexy in children: a comparison of caudal and regional blockade. J R Coll Surg Edinb. 1989;34(3):143-5.
[22] Dalens B, Hasnaoui A. Caudal anesthesia in pediatric surgery: success rate and adverse effects in 750 consecutive patients. Anesth Analg. 1989;68(2):83-9.
[23] Lim S, Ng Sb A, Tan G. Ilioinguinal and iliohypogastric nerve block revisited: single shot versus double shot technique for hernia repair in children. Paediatr Anaesth.
2002;12(3):255.
[24] Jagannathan N, Sohn L, Sawardekar A, Ambrosy A, Hagerty J, Chin A, et al. Unilateral groin surgery in children: will the addition of an ultrasound-guided ilioinguinal nerve block enhance the duration of analgesia of a single-shot caudal block? Paediatr Anaesth. 2009;19(9):892-8.
[25] Beyaz S, Tokgöz O, Tüfek A. Caudal epidural block in children and infants: retrospective analysis of 2088 cases. Ann Saudi Med. 2011;31(5):494-7.
[26] Polaner DM, Taenzer AH, Walker BJ, Bosenberg A, Krane EJ, Suresh S, et al. Pediatric regional anesthesia network (PRAN): a multi-Institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg. 2012;115(6):1353-64.
[27] Parvaiz MA, Korwar V, McArthur D, Claxton A, Dyer J, Isgar B. Large retroperitoneal haematoma: an unexpected complication of ilioinguinal nerve block for inguinal hernia repair. Anaesthesia. 2012;67(1):80-1.
[28] Amory C, Mariscal A, Guyot E, Chauvet P, Leon A, Poli-Merol ML. Is ilioinguinal/iliohypogastric nerve block always totally safe in children? Paediatr Anaesth. 2003;13(2):164-6.
[29] Jöhr M, Sossai R. Colonic puncture during ilioinguinal nerve block in a child. Anesth Analg. 1999;88(5):1051-2.

[30] Sarti A, Busoni P, Dellfoste C, Bussolin L. Incidence of vomiting in susceptible children under regional analgesia with two different anaesthetic techniques. Paediatr Anaesth. 2004;14(3):251-5.
[31] Geze S, Imamoglu M, Cekic B. Awake caudal anesthesia for inguinal hernia operations. Successful use in low birth weight neonates. Anaesthesist. 2011;60(9):841-4.
[32] Krane E, Haberkern C, Jacobson L. Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: prospective comparison of spinal and general anesthesia. Anesth Analg 1995;80:7-13.
[33] Somri M, Gaitini L, Vaida S, Collins G, Sabo E, Mogilner G. Postoperative outcome in high risk infants undergoing herniorrhaphy: comparison between spinal and general anaesthesia. Anaesthesia. 1998;53:762-6.
[34] Welborn L, Rice L, Hannallah R, Broadman L, Ruttiman U, Fink R. Postoperative apnea in former preterm infants: prospective comparison of spinal and general anesthesia. Anesthesiology 1990;72(838-42).
[35] Williams J, Stoddart P, Williams S, Wolf A. Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthesia. Br J Anaesth. 2001;86:366-71.
[36] Lacrosse D, Pirotte T, Veyckemans F. Bloc caudal associé à une anesthésie au masque facial (sévoflurane) chez le nourrisson à haut risque d’apnée : étude observationnelle. Ann Fr Anesth Reanim. 2012;31(1):29-33.
[37] Davidson AJ. Anesthesia and neurotoxicity to the developing brain: the clinical relevance. Paediatr Anaesth. 2011;21(7):716-21.
[38] Craven PD, Badawi N, Henderson-Smart DJ, O’Brien M. Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. Cochrane Database of Systematic Reviews. 2003(3).
[39] Bouchut JC, Dubois R, Foussat C, Moussa M, Diot N, Delafosse C, et al. Evaluation of caudal anaesthesia performed in conscious ex-premature infants for inguinal herniotomies. Paediatr Anaesth. 2001;11(1):55-8.
[40] Somri M, Tome R, Teszler CB, Vaida SJ, Mogilner J, Shneeifi A, et al. Does adding intravenous fentanyl to caudal block in children enhance the efficacy of multimodal analgesia as reflected in the plasma level of catecholamines? Eur J Anaesthesiol.
2007;24(5):408-13.
[41] Kokinsky E, Nilsson K, Larsson L. Increased incidence of postoperative nausea and vomiting without additional analgesic effects when a low dose of intravenous fentanyl is combined with a caudal block. Paediatr Anaesth. 2003;13:334-8.
[42] Khosravi MB, Khezri S, Azemati S. Tramadol for pain relief in children undergoing herniotomy: a comparison with ilioinguinal and iliohypogastric blocks. Paediatr Anaesth. 2006;16(1):54-8.
[43] Lloyd-Thomas A, Howard R. A pain service for children. Paediatr Anaesth. 1994;4:3-15.
[44] Mossetti V, Vicchio N, Ivani G. Local anesthetics and adjuvants in pediatric regional anesthesia. Curr Drug Targets. 2012;13(7):952-60.
[45] Shukla U, Prabhakar T, Malhotra K. Postoperative analgesia in children when using clonidine or fentanyl with ropivacaine given caudally. J Anaesthesiol, Clin Pharmacol. 2011;27(2):205-10.
[46] Tobias JD. Caudal epidural block: a review of test dosing and recognition of systemic injection in children. Anesth Analg. 2001;93(5):1156-61.

Categories
Guest Articles

The Federal Budget 2013 – 2014: An opportunity to deliver a health workforce that meets future healthcare needs

The Federal Budget 2013 – 2014 announcement and its expected impact on health The announcement of the Australian Federal Budget is one of the most important dates on the calendar for the healthcare industry. The Budget provides a clearer understanding of the funding priorities of the Federal Government and lays the foundation for healthcare investment. This upcoming Federal Budget, to be announced on 14 May 2013, comes at a crucial time, with pressure on the Federal Government to deliver a tight fiscal Budget, advance the National Disability Insurance Scheme (NDIS) and carefully navigate through issues of state and territory jurisdiction. Issues relating to medical graduates are particularly poignant, with protected teaching, health workforce capacity, and the provision of general medicine in the rural and remote setting critical areas that must be addressed in the upcoming Federal Budget. The challenges all medical colleges currently face relate to the provision of training that prepares trainees for the challenges ahead, the adoption of technology into education models, and the applicability of training across remote, regional and metropolitan communities and settings outside of the hospital.

The current state of the Australian health system

The health of Australia’s population is ranked among the best in the world. However, increasing life expectancy brings with it the challenges of an ageing population, particularly to a healthcare system that is designed for, and accustomed to, episodic acute and emergency care, and single disease presentations. Patient interactions with the healthcare system are now more regular and complex and healthcare professionals are commonly involved in delivering care across a range of settings, including acute and sub-acute hospitals on an inpatient or outpatient basis, the home, primary care clinics and aged care settings. Healthcare expenditure is ballooning and additional demands are being placed on an already strained health workforce. [1]

Jurisdictional funding and policy responsibilities and the public-private divide have resulted in a fragmented and siloed healthcare system. As a result, patients experience difficulty navigating through the system and specialist physicians confront challenges trying to integrate and coordinate with other members of the multidisciplinary team. There are opportunities to overcome these barriers to improve the healthcare system and health outcomes for all Australians, particularly in the context of National Health Reforms. Areas highlighted by the College as most impacting for medical graduates and physician trainees include the equitable distribution of the physician and trainee workforce, protected teaching, and issues of health workforce, specifically general medicine.

One of the greatest strengths of the Australian healthcare system is the increased numbers of medical students who will eventually undertake specialist physician training. Recognising that there are challenges associated with increased numbers, the RACP and other medical colleges will need to work with the Federal Government to ensure all medical graduates receive their desired and best possible experiences in the various training programs. Increased numbers of trainees will eventually equate to increased specialist physicians and other healthcare professionals. It will be important to ensure these numbers are mobilised effectively and are trained to operate in a number of different healthcare settings.

Protected teaching

There is a need for protected time for supervisors for training and education. In addition to the increased numbers of medical graduates entering physician training, improvements to the structure of the training programs in accordance with standards set by the regulators (the Medical Board of Australia and the Australian Medical Council) means that there is a need to increase the length of time for supervisors to support trainees in their learning. This has been identified as a key priority area by the RACP and many other Australian medical colleges ahead of the Federal Budget funding allocation in May 2013.

The RACP recommends the Australian Government work with the RACP, other medical colleges and jurisdictions to increase the capacity of specialist physicians to train the future physician workforce. Increased capacity could be achieved by facilitating the introduction of protected time for supervisors and trainees to undertake training activities, and facilitating an increase in the time needed for supervisors to be available to support trainees in their learning in the workplace. This includes attending supervisor training and professional development as well as allocated time to meet with trainees to review progress, provide advice and complete supervisor reports. A further key action is the facilitation of better training for supervisors, recognising that the supervisor role requires specific knowledge and skills.

Ensuring the equitable distribution of the physician and trainee physician workforce

The health workforce must consist of sufficient numbers and skill mix, and services must be fairly distributed across populations to manage the current and future healthcare needs of the Australian population. The specialist physician workforce must have capacity to train new specialist physicians and take the time to develop and improve knowledge and skills for the provision of high quality and safe clinical care.

People living in regional, rural and remote areas have some of the highest rates of complex and chronic disease. However, these populations have the poorest access to locally provided specialist healthcare. There is a need for specialist services to be distributed fairly across populations and located where they are needed the most. Vulnerable communities, particularly those that experience higher rates of long term illness, must be able to access specialist services without difficulty.

The RACP is seeking to work with the Australian Government to continue to support the redistribution of specialist physician services toward rural and non-hospital settings through Specialist Training Program (STP) placements. The RACP recommends the continuation of STP funding towards rural training places, rural salaries and ‘Rural Support Loading’ to supplement the additional costs incurred by trainees in rural areas. Additional measures put forward to the Government as part of Federal Budget priorities include the continuation of STP funding towards training places in community, non-clinical and ambulatory care settings and the continuation of STP funding towards posts in Aboriginal Controlled Community Health Services and Aboriginal Medical Services. Specialist training is heavily reliant on the skills and availability of clinician teachers and supervisors in the workplace. The STP provides a Commonwealth-funded annual salary contribution of $100,000 until 2015 for trainees in non-traditional settings.

In an integrated national healthcare system, healthcare practitioners would be able to provide timely and quality care in the setting that best meets patient needs, as summarised by the phrase “the right care, at the right time, by the right provider, in the right setting.” The current debate about future workforce shortages as well as the distribution of specialist physicians, which is often mismatched with patient needs, reinforces the importance of care delivered in all settings.

Indicators of a high-quality and highly functioning health system include the capacity to provide timely and safe care to patients in the setting that best meets their needs and preferences, and the ability to mobilise multidisciplinary teams to provide care in an integrated and coordinated manner.

The RACP strongly supports measures that equip medical graduates with the skills to manage the increasing prevalence of comorbid chronic disease in the community. This includes developing training pathways that enable more generalist and dual trained physician workforce that can respond to this shift in demand, as well as targeted distribution of the physician workforce, particularly to better meet the needs of rural and remote communities. This is particularly relevant for today’s medical graduates, who will play a significant role in shaping the future state of Australia’s healthcare landscape.

There is growing evidence to support the adoption of collaborative organisational arrangements for the provision of care in the Australian healthcare system. The development of formal arrangements that allow specialist physicians to regularly provide care to Aboriginal and Torres Strait Islander communities and older people in primary and aged care services to address unmet demand is imperative. To counter this unmet demand, the RACP recommends careful consideration and analysis of specialist medical services that could be delivered in primary, community and ambulatory settings.

The Australian Government must invest in cost-effective interventions tailored to redesign service delivery and widely promote a multidisciplinary team-based approach for the provision of chronic and acute care in the primary, community and ambulatory settings. As the physicians of the future, trainees and medical graduates play a vital part in the development of a cost-effective, equitable and high functioning healthcare system. Working collaboratively to develop models of healthcare that benefit and respond to all communities, age groups, and unique circumstances is key to addressing the complex challenges facing today’s healthcare landscape.

References

[1] Intergenerational Report 2010, Australia to 2050: Future Challenges, http://archive.treasury.gov.au/igr/igr2010/report/pdf/IGR_2010.pdf

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

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[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.

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 nonimmune 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
Feature Articles Articles

Emergency medicine in Australian medical student education

“The best way to predict the future is to invent it.” Alan Kay

Introduction

As the coalface of Australian healthcare, Emergency Medicine (EM) faces the growing healthcare challenges of the wider community. Today, these challenges form a unique ‘triple whammy’ – overseeing the implementation of the National Emergency Access Target (NEAT) or “4-hr rule”, in an effort to manage access block and emergency department overcrowding as a result of the increased care needs of an ageing population, whilst at the same time with limited resources attempting to maintain the quality of education and training of a burgeoning junior medical workforce. [1,2]

Amidst this conundrum, medical student EM education may sometimes be left in the shadows. [3,4] The unique arena of the emergency department with its volume, breadth and variety of undifferentiated patient cases not only provides countless learning opportunities for medical students but also allows them to contribute to healthcare teams in practical and meaningful ways. This ranges from assisting in initial assessments, to performing indicated procedures, to formulating discharges, and even research involvement. [5,6] All of which are useful and valuable skills favoured upon in a junior medical doctor and reduces the workload of the supervising team. [7-9] While some may argue that the general wards offer similar opportunities, the increasing attempts in improving efficiency and subspecialising medicine have led to the bulk of diagnostic and therapeutic interventions to be conducted in the emergency departments prior to acceptance by inpatient units. [4]

Students themselves find EM rotations extremely valuable, with many practical benefits for their future medical careers. [10] However, the already hectic and stressful EM work environment, coupled with enhanced time pressures from NEAT, increasing numbers of interns needing to complete an ED term, and the significant teaching and supervision requirements within EM departments may prove to be hurdles that limit the chances for medical students’ education. [11]

Thus, it may be prudent to re-examine this issue of our workforce challenges and to re-assess  medical student education.

  1. Could added investment in extension and evaluation of EM to medical students pique their interest in a future EM career?
  2. Would an increased focus on EM teaching better equip and innovate Australia’s future healthcare workforce?

Why is EM important in medical student education?

As a population-based specialty, EM education offers medical students a glimpse into the domain of public health. Patients present with illnesses and injuries that have high population prevalence, and presentations vary even across times of the day. Students are therefore exposed to a dynamic socioeconomic, cultural and demographic case mix. This serves to broaden not only the variety in conditions that students would see within an EM rotation, but also widens their perspectives on pertinent issues affecting different age groups in the Australian healthcare setting.

EM also provides an opportunity to learn about pre-hospital care, including co-ordinating ambulance and paramedic transfer services, retrieval, wilderness and disaster medicine.  Students encounter clinical scenarios they would not otherwise see such as occupational and environmental health, toxicology and trauma, and are also exposed to accident and injury surveillance, treatment and prevention.

EM has unique content areas that form the foundation of medical student training. In fact, EM exposure is seen as a form of clinical training assurance and a measured criterion for both students and junior doctors to be work-ready, and is considered essential and highly valuable as a core intern term in all states around Australia. [7]

With each undifferentiated presentation, students are encouraged to complete a focused history and examination, consider emergency interventions and prioritise differential diagnoses, rather than needing to pinpoint a correct diagnosis in a second. They then formulate streamlined investigation and management plans, and have opportunities to perform basic procedures which form part of the initial evaluation of many patients. Students can also receive positive feedback and critique from clinicians on their performance, and even observe and learn from their more senior colleagues in managing acutely ill patients. [4]

There are other unique benefits of students training in the ED environment. With the rollout of NEAT, clinicians may be increasingly pressured to make time-critical evaluations and decisions. Students would therefore not only be able to observe time and cost effective patient assessment strategies but also hone problem solving and task prioritisation skills. [12] The acute management of common ED presentations would be better appreciated as fewer patients stay in the ED for hours or days and are transferred to the wards within four hours. Furthermore, a minimum of 40% and up to 73.3% of patients within the ED are available for directed-learning purposed interaction with student doctors – a significantly higher percentage than inpatient wards. [4,13]

Many EDs now also contain short stay units (SSU) where patients requiring short admissions or periods of observation are managed. A multidisciplinary healthcare team is often involved in the care of these patients, and students are able to work with the team and are involved in allied health discussions and discharge planning meetings.

How can students learn more?

Access

Medical students are usually not rostered on overnight shifts due to a lack of senior medical staff and thus inadequate supervision. A 24-hour rostering of students may be one way to combat the need for more placement opportunities, provided it does not overload junior medical staff. Elective night shits have already been occurring though there is no current data evaluating medical students’ learning during those specific shifts. Nonetheless, there would be benefit in providing observational exposure to a different case-mix of patients, especially in resuscitation situations, where students can play a more hands-on role during night shifts.

E-learning

Simulation skills laboratories have been a proven tool in improving theoretical knowledge and procedural skills for medical students, especially in deteriorating patient or acute resuscitation scenarios. [14] These courses, along with other electronic resources can also be utilised for on or off-site learning. More traditional trauma training courses and more novel methods such as cadaver based simulation course for advanced emergency procedures have also proved useful in equipping medical students with basic and advanced procedural skills. [15]

Decision supports

Competency-based training including the use of logbooks and clinical pathways has been shown to improve quality of care in some areas of medicine. [16-18] Logbooks are currently used at various specialty training colleges including ACEM, and adoption for EM education can assist students to measure their abilities against a minimum standard. Medical diagnosis or treatment protocols or checklists can also guide students in developing a systematic approach to evaluating and treating various conditions.

How can students contribute more?

Previous research has shown the potential benefit that engaging medical students as paid assistants of the healthcare team can have on performance efficacy and workflow. Pilot projects have been tested in Germany and the USA. [8,9]

If introduced, a similar system within the EM departments where medical students assist in triaging patients, undertake basic procedures and complete preliminary paperwork alongside a nurse or rapid assessment clinician may expedite care and reduce waiting times for patients.  They could also aid in collating relevant medical information from GPs, specialists, residential care facilities and families. This would ease the paperwork burden for clinicians, improve efficacy of clinician-patient contact time and at the same time provide learning opportunities for students whilst collecting and synthesising information.

Medical students can also play an important role in academic aspects of EM. It is sometimes difficult for clinicians to allocate specific time for research whilst balancing patient care; thus students can assist in identification and recruitment of subjects, drafting of protocols and briefing of staff members on ongoing projects.

Where to from here?

The immediate challenges EM departments face should not deter EM clinicians’ involvement in training medical students for the future. [11] Rather, a collaborative effort with students to enhance EM learning will give future doctors a skillset applicable in any emergency scenario, regardless of specialty area.

As such, students’ feedback on EM rotations and learning techniques should be considered when planning EM curricula. Allocation of dedicated teaching time and educators along with adequate funding for implementation of various initiatives such as e-learning and simulation courses should also be made available for use.

Further research evaluating the current state of EM medical student education nationwide is crucial to identify key areas for improvement. Pilot projects testing novel ways such as those listed above to allow students to contribute to EM departments will also be beneficial to further evaluate innovative learning techniques.

Despite the added cost and effort required, EM training has proven invaluable for medical students and remains an essential part of their training. It is therefore highly recommended that EM continues to maintain a strong presence in medical students’ curriculum. [5]

Conflict of interest

None declared.

Acknowledgments

The authors would like to thank Dr Tony Kambourakis and Dr Simon Craig for their valuable assistance in guiding the development of this manuscript.

Correspondence

C Liew: cwlie2@student.monash.edu

References

[1] Braitberg G. Emergency department overcrowding: The solution to any problem is a matter of relativity. MJA. 2012;196(2):88-9.

[2] Chong A, Weiland TJ, Mackinlay C, Jelinek GA. The capacity of Australian ED to absorb the projected increase in intern numbers. Emerg Med Australas. 2010;22(2):100-7.

[3] Dowton SB, Stokes M, Rawstron EJ, Pogson PR, Brown MA. Postgraduate medical education: Rethinking and integrating a complex landscape.MJA. 2005;182(4);177-180.

[4] Celenza A. Evolution of emergency medicine teaching for medical students,Emerg Med Australas . 2006;18(3):219-220.

[5] Celenza A, Jelinek GA, Jacobs IG, Murray L, Graydon R, Kruk C. Implementation and evaluation of an undergraduate emergency medicine curriculum.  Emerg Med Australas. 2001;13:98–103.

[6] Aldeen AZ, Gisondi MA. Bedside teaching in the emergency department.Acad Emerg Med. 2006;13(8):860-6.

[7] (AMA). AMA. AMA Positional statement: Core terms in internship. 2007 [29 Feb 2012]; Available from: http://ama.com.au/node/2712.

[8] Schuld J, Justinger C, Kollmar O, Schilling MK, Richter S. Contribution of final-year medical students to operation room performance—economical and educational implications. Langenbeck Arch Surg. 2011;396(8):1239-44.

[9] Davis DJ, Moon M, Kennedy S, DelBasso S, Forman HP, Bokhari SA. Introducing medical students to radiology as paid emergency department triage assistants.JACR. 2011;8:710-5.

[10] Avegno JL, Murphy-Lavoie H, Lofaso D, Moreno-Walton L. Medical students’ perceptions of an emergency medicine clerkship: An analysis of self assessment surveys.IJEM. 2012;5(1):25. Epub [Epub ahead of print]

[11] Indraratna PL, Lucewicz A. Impact of the 4-hour emergency department target on medical student education.Emerg Med Australasia. 2011;23(6):784.

[12] Wald DA, Lin M, Manthey DE, Rogers RL, Zun LS, Christopher T. Emergency medicine in the medical school curriculum.Acad Emerg Med. 2010;17:S26-S30.

[13] Celenza A, Li J, Teng J. Medical student/student doctor access to patients in an emergency department.Emerg Med Australas. 2011;23(3):364-71.

[14] Langhan TS. Simulation training for emergency medicine residents: Time to move forward.CJEM. 2008;10:467-9.

[15] Tabas JA, Rosenson J, Price DD, Rohde D, Baird CH, Dhillon N. A comprehensive unembalmed cadaver based course in advanced emergency procedures for medical students.Acad Emerg Med. 2005;12:782-5.

[16] Taylor MD, Harrison G. Procedural skills quality assurance among Australasian College for Emergency Medicine fellows and trainees.Emerg Med Australas. 2006;18(3):268–275

[17] Nagler J, Harper MB, Bachur RG. An automated electronic case log: Using electronic information systems to assess training in emergency medicine.Acad Emerg Med . 2006;13:733-739.

[18] Chu T, Chang S, Hsieh B. The learning of 7th year medical students at internal medical – evaluation by logbooks. Ann Acad Med Singap. 2008;37:1002-7.

 

 

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Feature Articles Articles

Fiction and psychiatry: The tale of a forgotten teacher

“Wherever the art of medicine is loved, there is also a love of humanity.” -Hippocrates

Reading this declaration today, conjures an unsettling, or almost unpleasant feeling that this once foundational concept may today be lost in time.  A ‘love for humanity’, whilst still lingering in the minds of some clinicians has been largely side-lined by science, research, evidence based practice,  being mindful of patient’s rights, family criticisms and practicing medicine with caution against being sued or criticised ourselves. We may benefit to keep in mind the words of American, philosopher Will Durant, “Every science begins as philosophy and ends as art.”

Ironically, it seems that science may provide answers to the apparent diminution of humanity in medicine. A recent editorial advocated that empathy in medicine may have a neurobiological basis and therefore can be up-regulated through specific neurobiological correlated education methods, in order to enhance professionalism and compassion.[1,2] Suggestions such as these reflect society’s growing dependence, or perhaps near enslavement to science which may soon become a surrogate for what were once regarded as inextricable, innate, features of our humanity – empathy and wisdom.

Beveridge reminds us that, “Doctors need a deeper understanding of their patients that takes account of emotional and existential aspects.”[3] Literature offers us a multitude of human experiences that may serve to deepen our appreciation of the breadth of human consciousness. As T.S. Eliot stated, “We read many books, because we cannot know enough people.”[3]

Psychiatry is one field of medicine which demands a strong level of empathy and a sophisticated level of interpersonal communication. Psychiatry studies the human mind with its complexities of emotions, behaviours, motives, experiences and reactions. Crawford describes the existence of a ‘synergism’ between literature and psychiatry as they both focus on the human mind from two separate paradigms: first, a scientific, biomedical framework of medicine; second, an artistic, creative medium of fiction. He questions, despite this congruence, why does literature still ‘remain the poor relation of the medical textbook?’[4] The concept of two paradigms, or a dualisms of brain and mind is explored further by Australian philosopher David Chalmers who describes how these two entities are different and how understanding each one requires a unique method.[5]

It is at this junction, between clinical psychiatry and fictional literature that our journey begins. This essay will explore some of the reasons for why we, as students and health professionals should and should not engage in fictional reading. We will then delve into some literary examples that provide insight into mental illness.

Benefits of fiction

Reading fiction may allow us to better connect with individuals such as our patients emotionally by first connecting with fictional characters. Evans proposes that when we read for enjoyment, “Our defences are down – and we hide nothing from the great characters of fiction.”[6] He contrasts this to a doctor-patient interaction where doctors, “do [their] best to hide everything beneath the white coat, or the avuncular bedside manner.” Over many years, all that is left is a professional, clinical interaction at the cost of a personal connection with the patient. He reminds us that, “It is at this point where art and medicine collide, that doctors can re-attach themselves to the human race and re-feel those emotions which motivate or terrify our patients.”[6]

Psychiatry tends to place a greater emphasis on thought form when making diagnoses, whilst the patients are more concerned with thought content, even though a doctor may at times miss the subtleties in form too. Literature can make us more aware of the importance of the content to the individual and connect more closely with the patient’s experience. Sims illustrates this:

“The patient is only concerned with the content, ‘that I am pursued by ten thousand hockey sticks.’ The doctor is concerned with both form and content, […] in this case a false belief of being pursued. As far as the form is concerned the hockey sticks are irrelevant. The patient finds the doctor’s interest in form unintelligible and a distraction from what he regards as important. […] The nature of the content is irrelevant to the diagnosis.”[7]

The analysis of thought form leads us to a clinical diagnosis which justifies clinical interest in form over content; thought process over a patient’s narrative. Crawford hypothesises that with the increasing biomedical dominance in psychiatry, there is bound to be further marginalisation of content. He argues that in fiction, the content, which encompasses all human experiences, emotional responses and behaviours, is more valuable and effective in conveying an understanding about the narrative than the form.[4]

Shortcomings of fiction

Not everyone values literature in the context of medical progress – Wassersug proclaimed that, “Real medical progress has not been made by humanitarians but by doctors equipped with microscopes, scalpels, dyes [and] catheters, […] similarly psychiatry should be seen as a branch of the natural sciences.”[3] He argues that literature has nothing to offer to psychiatry, a field which should be led by advances in neurosciences, not narrative.

Reading has been described as a ‘selfish’ activity that can expand individual intellect but cannot instil a spirit of altruism or increased sensitivity towards others.[3] The physician Raymond Tallis illustrates how reading may in fact make us less empathetic; he quotes Tolstoy’s tale of an aristocratic woman weeping over a theatrical tragedy, while outside a real tragedy eventuates as her faithful coachman freezes to death. This anecdote highlights the ability of the arts to delude the woman, to believe herself to be sensitive, when in fact she is actually being inconsiderate.[3]  Some arguments against reading fiction may be valid. However, they are not sufficient to completely discredit the opportunity fiction provides us to expand our sense of enlightenment, self-development and inspiration in a way that a factual textbook simply cannot.

Fiction and mental illness

Literature is an instrument to present facets of mental illness that may not be captured through textbooks, lectures or case presentations. Oyebode suggests that fictional narrative achieves its aims by magnifying or exaggerating specific aspects of characters such as their mannerisms, behaviour or speech to make them stand out to the reader. Oyebode analyses Patrick McGrath’s Asylum to illustrate how delusional jealousy may be the result of multiple trivial everyday occurrences:

“Driven by the morbid processes to suppose that his wife was betraying him with another man, he had reasoned first, that they must have ways of signalling their arrangements, and second, that their activities must leave traces. He had then manufactured evidence of such signals and traces from incidents as banal as her opening a window as a motorbike was going past in the street below, and from phenomena as insignificant as a crease in a pillow or a stain on a skirt.”[8]

Oyebode presents a detailed, focussed magnification on the protagonist’s paranoid, obsessive thoughts about everyday occurrences. This allows the reader unrestricted access into the thoughts that occupy a person’s mind suffering with delusional jealousy.

Oyebode provides a glimpse into nihilistic thoughts through McGrath’s Spider:

“I was contaminated by it, it shrivelled me, it killed something inside me, made me a ghost, a dead thing, in short it turned me bad […] I wonder…what they will find when they cut me open (if I’m not dead)? An anatomical monstrosity surely.”[8]

The emotive and dark imagery in this writing serves to illuminate the depth of nihilism; the torment the protagonist faces at the mercy of his own mind. Once again, the account provides important insight into a paradigm of thought that may otherwise be foreign to an external observer.

Jenny Diski describes the experience of depression beautifully in Nothing Natural:

“Here it was again. Unmistakeably it. […] A physical pain in her diaphragm, a weight as if she had been filled with lead, the absurd difficulty of doing anything – automatic actions having to be thought out to be achieved: how do you get across the room, make the legs move, keep breathing, think carefully about it all. […] The unreasonable difficulty of everything made more unreasonable, more difficult knowing that nothing physical was wrong. […] Depression was an excess of reality: intolerable and unliveable.”[4]

This detailed deconstruction of depression exposes the destructive power of depression to render a person physically powerless whilst they are mentally completely aware of what is happening to them. Literature forms a bridge between the internal world of our patients and our global comprehension of their condition. This bridge elevates us from helpless bystanders to active and effective treating practitioners.

Sometimes the words of fictional characters may attack the reader directly, encouraging the reader to engage in self-reflection. The protagonist, from Kristin Duisberg’s The Good Patient, expresses that mental health practitioners:

“have chosen their profession to deny a terrifying truth other doctors accept – there are ills for which there is no cure.”[4]

At first glance this idea seems completely bizarre, as no psychiatrist believes they can cure all psychiatric conditions. However, it is hard to completely dismiss it without the thought lingering on in our subconscious. This attack stimulates some introspection to determine whether there may be any truth behind it at all. The words of this fictional character have the power to leap off the pages, and into our subconscious to question our role and limitations when treating patients with mental illness.

Literature tries to ‘de-pathologise’ mental illness as evidenced by Sally Vickers in The Other Side of You:

“We are most of us badly cracked and afraid that if we do not guard them with our lives the cracks will show, and will show us up, which is why we are all more or less in a state of vigilance against one another.”

By addressing this ‘cracked’ nature inherent in all of us, the author indirectly places all of us on a spectrum of mental illness. She implies, the only difference between mentally healthy and ill is where we stand on this spectrum. Concepts such as this break down the differences between ‘normal’ and ‘mentally ill’ and help liberate us from our own inbuilt stigmas against mental illness.

An extensive list of texts and their relation to mental illness can be found at www.madnessandliterature.org

Commentary

Literature, good TV and theatre for that matter, may not completely depict psychiatric psychosis or other psychiatric conditions in their entirety and complexity. They do however give us a glimpse into the differences between internalising (major depression, generalised anxiety and panic disorders, phobias) and externalising (alcohol and drug dependence, antisocial personality and conduct disorders) disorders.

We find ourselves in an age where the growth of information, triumphs of science and expansion of technology appears to be propelling us into a biomedical dominated practice of medicine. The question that we must ask ourselves is whether this scientific dominance is encroaching on our capacity for empathy, understanding and appreciation? Fictional literature may provide us with an opportunity to re-connect to our humanity in a way that no other medium can. Literature may not make us better diagnosticians, or change the value system of our profession, but it will make us question ourselves, our thoughts, and our perception of others. This new level of reflection and understanding can result in a more wholesome interaction with patients which will strengthen the therapeutic alliance between patient and doctor.

The study of humanities should not take priority over crucial clinical elements, but it can be used as an adjunct to clinical education. There is evidence to suggest benefit of reading already, and a number of medical schools have implemented medical humanity subjects and faculties because of their appreciation of its inherent value.[9-11] However, reading is something that is not restricted to the classroom; it cannot be tamed by our teachers and it has a timeless ability to touch us if we let it. Alexandra Trenfor writes, “The best teachers are those who show you where to look but don’t tell you what to see,” and fiction is like this teacher – it provides us with a narrative, but leaves its meaning and essence for us to discover ourselves.

Conflict of interest

None declared.

Correspondence

K Makhija: karan.makhija88@gmail.com

Reference

[1] Kaptein AA. et al., ‘Why, why did you have me treated?’: The psychotic experience in a literary narrative. Med Humanit. 2012; 37: 123-26.

[2] Riess H. Empathy in medicine-a neurobiological perspective. JAMA. 2010;304: 1604-5.

[3] Beveridge A. Should psychiatrists read fiction? Bri Jour of Psychiatry. 2003; 182: 385-87.

[4] Crawford P,Baker C, Literature and madness: fiction for students and professionals. J Med Humanit. 2009; 30: 237-51.

[5] Chalmers DJ. The puzzle of conscious experience. Scientific American. 1995;volume?: 62-68.

[6] Evans M, Greaves D, Exploring the medical humanities. BMJ. 1999: 319: 1216.

[7] Sims A. Symptoms in the Mind. 2003; Philadelphia: Saunders/Elsevier Science Ltd.

[8] Oyebode F. Fictional narrative and psychiatry. Advances in Psychiatric Treatment. 2004;10: 140-45.

[9] Shafer A, Borkovi T,  Barr J. Literature and medical interventions: An experiential course for undergraduates. Fam Med. 2005; 37(7): 469-71.

[10] State of the Field Committee, Arts in healthcare. Washington DC: Society for the Arts in Healthcare, 2009.

[11] Bonebakker V. Literature & medicine: Humanities at the heart of health care: A hospital-based reading and discussion program developed by the Maine Humanities Council. Academic Medicine. 2003; 78(10): 963-67.

 

 

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Feature Articles Articles

Legalising medical cannabis in Australia

Introduction

Cannabis was first used in China around 6,000 years ago and is one of the oldest psychotropic drugs known to man. [1] There are several species of cannabis, the most common are Cannabis sativa, Cannabis indica and Cannabis ruderalis. [2] The two main products that are derived from cannabis are, hashish – the thick resin of the plant, and marijuana – the dried flowers and leaves of the plant. [1] Cannabis contains over 460 chemicals and 60 cannabinoids (chemicals that activate cannabinoid receptors in the body). [1,2] The major psychotropic constituent of cannabis is known as delta-9-tetrahydrocanabinol (THC); others include cannabinol and cannabidiol (CBD).

Cannabinoids exert their effect throughout the body through binding with specific cannabinoid receptors. There are two types of cannabinoid receptors found in the body: CB1 and CB2. Both are G-protein coupled plasma membrane receptors. The CB1 receptors are mostly found in the central nervous system, whilst CB2 receptors are mainly associated with immunological cells and lymphoid tissue such as the spleen, tonsils, and thymus. [3,4]

Delta-9-tetrahydrocanabinol (THC) and other cannabinoids are strongly lipophilic and are rapidly distributed around the body. [5] Because of its strong lipophilic nature cannabinoids accumulate in adipose tissue and have a long elimination time of up to 30 days, although the psychoactive effects generally wear off after a few hours. Medical cannabis can be dispensed and taken in a variety of ways including as a herbal cigarette, ingestible forms, or as herbal tea. However, marijuana cigarettes are commonly preferred as they provide higher bioavailability. [5]

Medical marijuana users represent a large range of ages, levels of education attainment, employment statuses, and racial groups. [6] A Californian study examining medical marijuana use showed 76.6% of medical marijuana users use seven grams of marijuana or less per week. Therefore, the majority of medical marijuana users are likely to consume amounts equivalent to mild to moderate recreational cannabis use. [6]

The rescheduling of cannabis in Australia draws strong debate and opinions from both sides of the issue. This article will provide an overview of the most popular arguments for and against the legalisation of cannabis for medicinal purposes.

The legal status of medical marijuana in Australia

Currently cannabis is a Schedule nine drug in all Australian states and territories, placing it in the same category as drugs like heroin and lysergic acid diethylamide (LSD). [7] Legally, drug scheduling in Australia is a state issue, however, all states abide by the federal government’s scheduling of cannabis as a Schedule nine drug, as per the Standard for the Uniform Scheduling of Medicines and Poisons. [7,8] The use of a drug which is classified as Schedule nine for recreational or medical purposes is illegal and a criminal offence. Research into cannabis in Australia is highly restricted. [7] Cannabis use is common in Australia with approximately 40% of Australians aged fourteen years or older saying they have used cannabis, and over 300,000 Australians using it daily. A number of Australians are already self-medicating with cannabis for a range of complaints including chronic pain, depression, arthritis, nausea, and weight loss. However, these people risk legal action from authorities, particularly if cultivating their own cannabis. Moreover, if they purchase cannabis from a dealer they also face quality and supply issues. [9] Proponents of medicinal cannabis envisage a system similar to other drugs of dependence, like opiates, whereby holders of a valid prescription will be able to purchase or access the drug but where recreational use of the drug would still be illegal.

A number of countries have decriminalised cannabis for medical purposes such as the Netherlands, Israel, eighteen states in the United States of America (USA), Canada and Spain. [10] However, the drugs known as Dronabinol (containing just THC), Nabilone (containing a synthetic analogue of THC) and Nabiximols (a spray containing CBD and THC) are available as Schedule eight drugs throughout Australia. [7] Schedule eight drugs are drugs which have a high likelihood for abuse and dependence and require regulation in their distribution and possession. [7,8] However, some claim that these preparations lack many of the cannabinoids found in natural cannabis plants and this leads to different physiological and therapeutic effects compared to natural cannabis. [4] Public support in Australia for medical cannabis is very high with a survey finding 69% of the public supporting the use of medical cannabis and 75% supporting more research into the medical potential of the drug. [11]

Arguments for legalisation

Pain relief

Marijuana has potent analgesic properties which can be used in pain relief for a variety of conditions that can cause intense pain, such as cancer pain and acquired immunodeficiency syndrome (AIDS). Marijuana may even provide superior pain relief when compared to opiates and opioids. A parallel study in the United Kingdom (UK) compared the use of a THC and CBD extract, a THC only extract, and a placebo in the treatment of cancer pain. It found that a THC:CBD mixture (such as that found naturally in the cannabis plant) is efficacious for the relief of advanced cancer pain that is not adequately controlled  by opiates alone. [4] Therefore, the legalisation of medical cannabis could relieve pain and improve the quality of life for severely ill patients suffering from a range of painful conditions.

Appetite stimulation

It has been proven in animal studies that THC can have a stimulating effect on appetite and lead to an increase in food intake. [2,5,12,13] There are a large number of clinical applications for THC for appetite stimulating purposes. Conditions which can cause cachexia (uncontrolled wasting) such as HIV/AIDS, cancer, multiple sclerosis (MS), could be treated with THC to stimulate the patient’s appetite, increase food uptake, restore weight, and improve the strength and wellbeing of the patient. [2,13] Human trials in the 1980s which involved healthy control subjects inhaling cannabis found that the cannabis caused an increase caloric intake of 40%. [14] The legalisation of cannabis for medical purposes could help improve both health outcomes and the quality of life in patients suffering from a range of conditions.

Anti-emetic

In Canada and the USA, dronabinol and nabilone have been used in the treatment of chemotherapy induced nausea and vomiting since the 1980s. [15] A systematic literature review found that cannabinoids were more effective than established anti-emetic drugs in its treatment. [16] By reducing or eliminating the often debilitating and painful symptoms of chemotherapy induced nausea and vomiting, medical cannabis is hoped to improve the quality of life for the patient and their family. A reduction in the vomiting and pain associated with chemotherapy may also cause an increase in adherence to chemotherapy by cancer patients and result in better patient outcomes. [2,13] Therefore, the rescheduling of cannabis could prove as a highly effective anti-emetic for cancer patients and could even improve their prognosis by encouraging adherence to chemotherapy.

Neurological conditions

Cannabis may also be used to lessen or alleviate an entire range of symptoms associated with MS and other neurological conditions. A Canadian randomised, placebo-controlled trial investigating the use of smoked cannabis for MS-related muscle spasticity found that cannabis was superior to the placebo in reducing pain and spasticity. [17] Another trial conducted in Canada on the use of smoked cannabis for chronic neuropathic pain found that an inhalation of the cannabis formulation prepared for the trial three times daily for five days reduced pain intensity, improved the quality of sleep, and had minimal adverse effects. [18] The legalisation of medical cannabis could therefore make a significant difference to the lives of the thousands of Australians suffering MS and many other neurological conditions.

Safety and overdosing

Cannabis may also serve as an incredibly safe alternative to groups of medications prescribed for pain, such as opiates. The CB1 cannabinoid receptors are the main receptors responsible for the analgesic effects of cannabis and are located in the brain. However, they are in very low numbers in the regions of the brain stem co-ordinating cardiovascular and respiratory control. [2,19] This means it is essentially impossible to overdose from cannabis. [5] However, opioid receptors are located in this brain stem region hence signifying that opioids can interfere with cardiovascular and respiratory functions and lead to death. [19,20] Prescription opioid deaths are a small but concerning issue throughout developed nations. For example, in 2005 there were over 1,000 deaths related to prescribed oxycodone in the US. [20] Medical marijuana may offer a safer alternative form of pain relief as it removes the risk of accidental overdose which can lead to death.

Arguments against legalisation

Cannabis use and psychiatric disorders

A longstanding argument against the medical use of cannabis has been that exposure to cannabis can lead to the development of psychiatric disorders, namely schizophrenia. A Scottish systematic review of eleven studies investigating the link between marijuana use and schizophrenia supported this view and found that cannabis use did appear to increase the risk of schizophrenia. [21] Another study has also shown that there is an association between heavy cannabis use and depression. [22] Further effects of cannabis induced psychosis can include self-harming and self-mutilating behaviours. [23,24] The relationship between cannabis use and mental health issues appears to be dose-related with higher amounts of marijuana use related to more severe psychiatric complications. [21,22] Some say it would be unethical to prescribe a patient cannabis when there is a risk of the patient developing mental illness and potentially harming themselves or others. Particularly, when there are other drugs available without such adverse effects on mental health and stability.

Public safety

With the legalisation of medicinal cannabis come clear public safety concerns, particularly in the areas of vehicle and pedestrian safety. Cannabis affects the brain and can cause feelings of disorientation, altered visual perception, hallucinations, sleepiness, and poorer psychomotor control. [5,19] A study conducted in California found that on a particular evening, 8.5% of motorists had THC in their system and that holders of a medical cannabis permit were significantly more likely to test positive to THC than those who did not hold a permit. [25] It has also been shown that drivers using cannabis had about three to seven times the risk of being in a motor car collision than drivers who were not using cannabis. [26] However, it is interesting to note that those driving under the influence of alcohol were at a higher risk of having a collision than those using cannabis. [27] Also interesting is the fact that after medical marijuana programs were instituted in the US, traffic fatalities decreased nine percent across the sixteen states which had programs at the time of the study; this is believed to be due to a substitution of alcohol with marijuana. [27,28] Pedestrians and cyclists who are prescribed cannabis are also at higher risks of being injured in a collision. In terms of non-vehicular injuries, an American study showed cannabis use was associated with an increased risk of injuries from causes such as falls, lacerations, and burns. [29] Hence the legalisation of medical cannabis not only poses a risk to the personal safety of the patient but also to the physical safety of the wider community.

Drug diversion

Given the popularity of cannabis as a recreational drug, there is always the risk of wide scale drug diversion occurring–that is people without a prescription for cannabis gaining access to the drug. This can happen in a number of ways like a patient sharing their medication with others or the patient selling their medication. In America diversion of medical marijuana is an increasing issue, particularly amongst adolescents. A study in the state of Colorado in the USA found that out of a group of 164 adolescents at a substance abuse treatment facility, 74% had used someone else’s medical marijuana, with the mean number of times the adolescents had used someone else’s medical marijuana being over 50. [30] Illicit use of cannabis for non-medical purposes exposes people to the damaging physical, mental and social impacts of drug use. There are clear questions surrounding how this would be prevented and how young adults especially could be prevented from accessing cannabis due to diversion. It must be asked whether it is ethically responsible to reschedule marijuana given that such a large number of other people, particularly adolescents, will have access to someone else’s medical cannabis.

Addictiveness and dependence

The legalisation of cannabis as a medication has the potential to cause patients to develop an addiction to the drug and possible dependence. Cannabis dependence is a recognised psychiatric disorder and it is estimated that over one in ten people who try marijuana will become addicted to it at some point. [31] Although dependence to marijuana may be lower than other drugs like, heroin, cocaine and alcohol, users can still face withdraw symptoms including sleep difficulty, cravings, sweating and irritability. [5,32] With the potential of people becoming addicted to medical cannabis and with scarring consequences for their personal life some say it is ethically questionable to subject people to it in the first place.

Availability of cannabinoid and synthetic cannabinoid drugs

Those opposed to cannabis being rescheduled for medical purposes claim that the availability of cannabinoid and synthetic cannabinoid drugs already in Australia namely, Dronabinol, Nabilone and Nabiximols, makes legalising medical cannabis unnecessary. They state that these drugs contain many of the same compounds as cannabis and can be used for treating many of the same conditions. [13] For example, Dronabinol has been shown to be effective in relieving patients suffering chronic pain which is not fully relieved by opiates. [33] Therefore, the cannabinoid medications which are already available in Australia may provide many of the same therapeutic benefits offered by cannabis, and as such rescheduling cannabis would be unnecessary.

Carcinogenicity

Whether marijuana smoke causes cancer, in particular lung cancer, is a subject of much debate and research itself. It is well established that tobacco smoke is carcinogenic and deeply damaging to overall health. [34] With marijuana containing many of the same carcinogens as tobacco, and often being in cigarette form, it is not unreasonable to expect similarly adverse results with cannabis use. [5,35] However, a case-control study by Hashibe et al. [36] found that there was not a strong relationship between marijuana use, even in heavy amounts, and the incidence of oesophageal, pharyngeal, laryngeal, and lung cancer. Some evidence exists, showing that cannabinoids may in fact kill some cancers such as gliomas, lymphomas, lung cancer and leukemia. [37-39] Despite evidence that marijuana smoke contains mutagenic and carcinogenic chemicals, epidemiologically this was not confirmed to be the case. [35,36] Overall the carcinogenic or cancer-fighting properties of marijuana remain unclear and contradictory. More long-term, large population research should be conducted so that the seemingly contradictory nature of the drug can be better understood. [36]

Recommendation

Cannabis offers exciting possibilities for patients afflicted by cancer, HIV/AIDS, MS, chronic pain and other debilitating conditions. Although medical marijuana programs face several obstacles, the benefits offered by medical marijuana and the positive impact this drug could have on the lives of thousands of patients and their families make a strong case for its consideration. The potential drawbacks can be minimised or even overcome through a number of measures, including: the close medical supervision of patients (e.g., proper patient education and monitoring), the creation of  appropriate infrastructure (e.g., medical marijuana dispensaries, as seen in California) and the creation of laws and policies that are not only supportive of medical marijuana patients but will also, minimise the risk the drug poses to the public (e.g., strict penalties for medical marijuana diversion).

Conflict of interest

None declared.

Correspondence

H Smith: hamish.smith@y7mail.com

References

[1] McKim WA. Drugs and behavior: An introduction to behavioral pharmacology 4th ed. Upper Saddle River: Prentice-Hall Publishing; 2000.

[2] Amar MB. Cannabinoids in medicine: A review of their therapeutic potential. Journal of Ethnopharmacology. 2002;105(1):1–25.

[3] Sylvaine G, Sophie M, Marchand J, Dussossoy D, Carrièr D, Caryon P, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 2005 Apr;232(1):54–61.

[4] Johnson JR, Burnell-Nugent M, Lossignol D, Gaena-Morton ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010 Feb;39(2):167-79.

[5] Ashton CH. Pharmacology and effects of cannabis: A brief review. Br J Psychiatry. 2001 Mar:178(2):101-6.

[6] Reinarman C, Nunberg H, Lanthier F, Heddleston T. Who are medical marijuana patients? Population characteristics from nine California assessment clinics. Journal of Psychoactive Drugs. 2011 Jul 43;2:128-35.

[7] National Drugs and Poisons Schedule Committee. Standard for the uniform scheduling of drugs and poisons No. 23. Canberra (ACT): Therapeutic Goods Administration; 2008 Aug. 432 p.

[8] Moulds RF. Drugs and poisons scheduling. Aust Prescr [Internet]. 1997 [Cited 7 Feb 2013];20:12-13. Available from: http://www.australianprescriber.com/magazine/20/1/12/3#qa

[9] Swift W, Hall W, Teeson M. Cannabis use and dependence among Australian adults: Results from the national survey of mental health and wellbeing. Addiction. 2001 May;96(5):737–48.

[10] Marijuana Policy Project (MPP). The Eighteen States and One Federal District With Effective Medical Marijuana Laws. Washington (DC): MPP; 2012 Dec. 19 p.

[11] National Institute of Health and Welfare. The National Drug Strategy Household Survey 2011. Australian Government: Canberra. 2012.

[12] Mechoulam R, Berry EM, Avraham Y. Endocannabinoids, feeding and suckling- from our perspective. Int J Obes. 2006 Apr; 30(1):24-8.

[13] Robson P. Therapeutic aspects of cannabis and cannabinoids. Br J Psychiatry. 2001 Feb;178:107-15.

[14] Foltin RW, Fischman MW, Byrne MF. Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite. 1988 Aug;11(1):1-14.

[15] Sutton IR, Daeninck P. Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J Support Oncol. 2006 Nov;4(10):531-5.

[16] Tramèr MR, Carroll D, Campbell FA. Cannabinoids for control of chemotherapy induced nausea and vomiting: Quantitative systematic review. BMJ. 2001 Jul;323(7303):16-21.

[17] Corey-Bloom J, Wolfson T, Gamst A. Smoked cannabis for spasticity in multiple sclerosis: A randomized, placebo-controlled trial. CMAJ. 2012 Jul;184(10):1143-50.

[18] Ware MA, Wang T, Shapiro S. Smoked cannabis for chronic neuropathic pain: A randomized controlled trial. CMAJ. 2010 Oct;182(14):694-701.

[19] Adams IB, Martin BR. Cannabis: Pharmacology and toxicology in animals and humans. Addiction. 1996 Nov;91(11):1585-1614.

[20] Paulozzi LJ, Ryan GW. Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med. 2006 Dec;31(6):506-11.

[21] Semple DM, McIntosh AM, Lawrie SM. Cannabis as a risk factor for  psychosis: Systematic review. J Psychopharmacol. 2005 Mar;19(2):187-194.

[22] Degenhardt L, Hall W, Lynskey M. Exploring the association between cannabis use and depression. Addiction. 2003 Nov;98(11):1493-1504.

[23] Khan MK, Usmani MA, Hanif SA. A case of self amputation of penis by cannabis induced psychosis. J Forensic Leg Med. 2012 Aug;19(6):355-7.

[24] Serafini G, Pompili M, Innamorati M, Rihmer Z, Sher L, Girardi P. Can cannabis increase the suicide risk in psychosis? A critical review. Curr Pharm Des. Jun 2012;18(32):5165-87.

[25] Johnson MB, Kelley-Baker T, Voas RB, Lacey JH. The prevalence of cannabis-involved driving in California. Drug Alcohol Depend. Jun 2012;123(1-3):105-9.

[26] Ramaekers JG, Berghaus G, van Laar M, Drummer OH. Dose related risk of motor vehicle crashes after cannabis use. Drug Alcohol Depend. 2004 Feb;73(2):109-19.

[27] Sewell RA, Poling J, Sofuoglu M. The effect of cannabis compared with alcohol on driving. Am J Addict. 2009;18(3):185-93.

[28] Anderson DM, Rees DI. Medical marijuana laws, traffic fatalities, and alcohol consumption. Denver (CO): Institute for the Study of Labor. 2011  Nov. 28 p.

[29] Gerberich SG, Sidney S, Braun BL, Tekawa IS, Tolan KK, Quesenberry CP. Marijuana use and injury resulting in hospitalisation. Annals of Epidemiology. 2003 Apr;13(4):230-7.

[30] Salomonsen-Sautel S, Sakai JT, Thurstone C, Corley R, Hopfer C. Medical marijuana use among adolescents in substance abuse treatment. J Am Acad Child Adolesc Psychiatry. 2012 Jul;51(7):694–702.

[31] Hall W, Degenhardt L, Lynskey M. The health and psychological effects of cannabis use. Canberra (ACT): Commonwealth Department of Health and Ageing; 2001.

[32] Budney AJ, Vandrey R, Moore BA, Hughes JR. Comparison of tobacco and marijuana withdrawal. J Subst Abuse Treat. 2008 Dec;35(4):362-68.

[33] Narang S, Gibson D, Wasan AD, Ross EL, Michna E, Nedeljkovic SS, et al. Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. The Journal of Pain. 2008 Mar;9(3):254-64

[34] Thun MJ, Henley SJ, Calle EE. Tobacco use and cancer: An epidemiologic perspective for geneticists. Oncogene. 2002 Oct;21(48):7307-7325.

[35] Hecht SS, Carmella SG, Murphy SE, Foiles PG, Chung FL. Carcinogen biomarkers related to smoking and upper aerodigestive tract cancer. J Cell Biochem Suppl. 1993 Feb;17(1):27-35.

[36] Hashibe M, Morgenstern H, Cui Y, Tashkin DP, Zhang ZF, Cozen W, et al. Marijuana use and the risk of lung and upper aerodigestive tract cancers: Results of a population-based case-control study. Cancer Epidemiol Biomarkers. 2006 Oct;15(1):1829.

[37] Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA. Antineoplastic activity of cannabinoids. J Natl Cancer Inst. 1975 55:597-602.

[38] McKallip RJ, Lombard C, Fisher M, Martin BR, Ryu S, Grant S, et al. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood. 2002;100:627-34.

[39] Sanchez C, de Ceballos ML, del Pulgar TG, Rueda D, Corbacho C, Velasco G, et al. Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res 2001, 61:5784-89.

 

 

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Articles Feature Articles

The history of breast cancer surgery: Halsted’s radical mastectomy and beyond

Breast cancer is common. One in eight Australian women will be diagnosed by the time they turn 85, and it has been estimated that this year in Australia approximately 14,600 women will receive the diagnosis, around 40 women each day. [1] A significant proportion will undergo surgery, mostly as the first means of treatment. Over the past forty years many advances have been made in the surgical approach to breast cancer. [2] New techniques and approaches have been developed and efforts for further improvements are ongoing. This article will explore the journey that breast surgery has undergone and what we can learn from its evolution.

William Halsted (born 1852) was an American surgeon whose contributions have influenced surgical principles to this day. [3] He is considered one of the ‘Big Four’ founding physicians of John Hopkins Hospital. [4] He pioneered the use of the hospital chart, advocated careful handling of tissue during surgery and stressed the importance of haemostasis. [3-6] His name is also synonymous with the radical mastectomy that he introduced in 1882. [3] At that time attempts at breast surgery had resulted in poor long term results and prognosis. [6,7] This new surgical approach was revolutionary in the treatment of breast cancer. The radical mastectomy was implemented for breast cancer no matter the size of the tumour, type, or the patient’s age. [8] It typically involves removal of all breast tissue, axillary lymph nodes and both pectoralis muscles. [6] It often results not only in severe disfigurement of the patient but also weakened arm function and disabling lymphoedema. [9] Whilst revolutionary at the time it was pioneered by Halsted, it was still widely used in the 1970s with a ‘one size fits all’ approach. [8] That approach is very different to the one taken today. [2,10,11]

While there had been some exploration of modifications to the procedure, such as sparing of the pectoralis muscles, as well as further dissection with removal of the internal mammary nodes, the surgical approach to breast cancer remained relatively static for more than eighty years. [8] Although there are many potential reasons this state of inactivity is surely multifactorial. Feminist authors have claimed that the mastectomy was not altered by male surgeons because of the power and control it gave them; that they had no understanding of the importance of a woman’s breast to a woman and treated patients in response to this view. [12] Others have suggested that Halsted was held in such high regard that no one dared alter his procedure, with surgeons ‘indoctrinated’ into his way of thinking. [12,13] Perhaps it is also that the nature of the disease affected how it was approached, with surgeons hesitant to make changes to a procedure they believed could save the lives of countless women. This seemed to be the case for Halsted himself who suggested, “After all, disability, ever so great, is a matter of very little importance as compared with the life of the patient.” [6] It must be acknowledged that in Halsted’s time there was no method of grading or staging cancers as there is now, a problem he recognised stating, “the importance of such a classification, if it were to any extent possible, is so evident that it is unnecessary to emphasize it.” [7] Had he had such information available to him his approach to individual cases may have varied greatly.

Alterations to the mastectomy were taken cautiously. There were forays into and case reports of the super-radical mastectomy, simple mastectomy and use of radiation therapy, as well as some use of simple excision; however no clear evidence as to the differences was available. [8] In 1969 the World Health Organisation approved a randomised control trial comparing radical mastectomy to the ‘quadrantectomy’. [8] Recruitment began in 1973 of patients staged with T1N0 disease who were aged less than 70 years. The quandrantectomy was combined with complete axillary dissection and postoperative radiotherapy. Early data demonstrated no difference in regards to survival rates, and the similarities in the long term survival rates were confirmed in data released in 2002. [8] In 1971 Fisher et al commenced a randomised trial comparing the radical mastectomy with total mastectomy with or without radiotherapy. [14] Studies such as these heralded the advent of breast conserving surgery and the acknowledgement that routine radical mastectomy may not always be the most appropriate surgical management.

Halsted proposed that although breast cancer begins as a local disease, it spreads in a contiguous manner away from the primary site through the lymphatic system. [6,15] This proposal led to his emphasis on aggressive locoregional treatment to prevent further spread. [6,7,12,15] This principle, however (known as the ‘Halsted Theory’), was also critical in introducing the concept of a sentinel node in relation to breast cancer. [15] Research into the sentinel node led to the use of the sentinel node biopsy which has dramatically influenced surgical management and outcomes for patients. One of the first studies demonstrating the benefits of lymphatic mapping for breast cancer was published by Guiliano et al in 1994. [16] Since that time the evidence, understanding and surgical skills in this area have grown rapidly.

Modern day surgery for breast cancer has changed significantly compared to that performed in the 1970s. The combination of breast conserving surgery alongside a sentinel biopsy allows patients to be left with good cosmetic results. [17,18] Oncoplastic techniques such as remodelling mammoplasty are also being utilised to improve cosmetic outcomes without compromising adequate tumour removal. [19,20] There is still however an appropriate place for the mastectomy. [20] Breast conservation is desirable, but needs to be acceptable cosmetically and not result in compromise to local control of the disease or survival benefit. [17,19,20] If local recurrence does occur following breast conservation, then salvage mastectomy is considered the standard approach, with salvage breast-conserving surgery only currently appropriate for consideration in select patients. [21]

Reconstructive breast surgery is an important part of management utilised by surgeons today. It is significant in improving the psychological morbidity associated with breast cancer surgery, particularly following mastectomy. [2,22] Once again Halsted had an influence in this area of breast surgery. He believed reconstruction was a “violation of the local control of the disease”. [10] Although there were a few early attempts at breast reconstruction by the likes of Czerny, Tanzini and Ombredanne, [23-25] the opinion put forward by Halsted and the view that local recurrence may not be detected if reconstruction occurred caused it to be avoided. [2,10] It seems, however, that surgical exploration of reconstructive procedures during this period was considered more than the possibility of breast conservation was. [8,10] This supports the view that surgeons at the time believed the mastectomy was crucial to life saving treatment and it was this belief that prevented progress to other initial surgical approaches. [13]

Following the introduction of the mastectomy in 1882 there were surgeons willing to attempt reconstructions to improve the quality of life of their patients. [2,10,22] In 1963 these efforts were bolstered by the silicone gel breast implant introduced by Cronin and Gerow. [26] In 1971 Snyderman and Guthrie placed an implant under the chest wall immediately following a mastectomy, as opposed to the delayed technique that had been used, and this was then accepted as the new technique. [27] In 1982 Radovan introduced the concept of skin expanders for those with significant skin deficits so that these patients too could be eligible for reconstructive surgery. [28] Following this skin-sparing mastectomies were introduced, with results demonstrating similar rates of local recurrence. [29] There have also been advances with the use of flaps as a method of reconstruction. [2,10] In regards to reconstruction of the nipple-areola complex, tattooing is now commonplace as initially suggested by Becker in 1986. [30] Today a woman who thirty years ago would have been left with almost no chance of reconstruction can have a relatively symmetrical result. Decisions relating to the method of reconstruction depend on many variables, however it can be seen that important progress has been made in this area of breast surgery. [2,10] This can improve patient perceptions towards treatment and significantly improve their quality of life. [2,22]

The evolution of breast cancer surgery demonstrates important principles when evaluating any surgical procedure. No matter what procedure is undertaken, the most appropriate management needs to be carefully considered with clear clinical reasoning and evidence where available. Despite this there are also many elements which need to be considered when deciding what is most suitable, not all of which are clear without a thorough understanding of both the patient being treated and the disease. The disease cannot be treated in isolation but must be regarded in consideration of the patient’s wishes, and often in regards to other health issues. This is especially true in oncological surgery. Treatment decisions cannot often be made simply or alone. They are best made by the patient and the surgeon as part of a multidisciplinary team. [2,22] With regard to breast cancer the tumour itself plays a critical role – its type, size, determination of its spread to lymph nodes or metastatic sites, and whether it is hormonally responsive. [2,22] The size of the tumour is crucial in determining operability, especially alongside a consideration of the size of the breast itself. Tumour size, breast size and the location are important when assessing for the likelihood of future local recurrence as well as the impact on cosmetic outcomes. [2,11,17]

For the appropriate management to be undertaken the surgeon must obtain as much information as possible. The patient’s family history and potential for a recognisable genetic factor requires thought. [11] Genetics play an increasingly important role in the management of patients with breast cancer. Along with the well-known BRCA1 and BRCA2 mutations, there are other unidentified genes which lead to strong familial associations. [31] Knowledge of these factors impacts on decisions regarding the surgical management of a particular patient as well as other forms of treatment.

Cost and availability of treatment options are also important in the surgical management of breast cancer. Cost is not often seen to impact on the treatment patients receive in Australia, however it can be overlooked, as can the availability of services and travel required to undergo particular surgical options. [2] These factors are much more pronounced in other parts of the world where only the exceptionally wealthy may be eligible for surgery. [32] It is important to consider the impact of a particular surgical treatment on the need for ongoing follow up and the level to which this will be required. [2,11] No matter which surgical approach is taken it is vital that realistic expectations of the prognostic as well as cosmetic results are discussed with each patient prior to surgery.

Surgical excision deals with local, known disease and comes alongside radiotherapy, chemotherapy, hormonal therapy and biological agents where appropriate. [11,22] These other treatment modalities impact on both prognosis and cosmetic results. [2,11,17,18,22] The role of surgery must be considered in relation to these other factors. Management options for breast cancer will continue to expand in coming years as current therapies improve and new ones emerge, requiring ongoing collaboration. [33]

At a multidisciplinary team (MDT) meeting the many stakeholders involved in a patient’s treatment come together. [11,22] No matter which path is chosen for each area of management, it is done in consultation with other experts, with each responsible for justifying their position. [33] Communication barriers are broken down and the full clinical picture is able to be understood by all involved. Although there is variation worldwide as to how MDTs are run, it is perceived that they improve clinical decision making, treatment quality and the practice of evidence based medicine. [33] Interestingly, Halsted himself viewed it as important that the surgeon had an intimate awareness of the pathology which he excised, writing

“There is a gap between the surgeon and pathologist which can be filled only by the surgeon. The pathologist seldom has the opportunity to see diseased conditions as the surgeon sees them. A tumor on a plate and a tumor in the breast of a patient, how different!” [7]

Halsted seemed to advocate that the surgeon’s interest and understanding of the pathology was more significant than that of the pathologist. The recognition of multi-disciplinary meetings is that all parties have significant “incentive” (as Halsted put it), [7] and by working together the gaps between the theatres, the laboratory and the chemotherapy centre can be closed.

The radical mastectomy is now famous for its brutality. [12] Despite its poor reputation today, by bringing it into existence Halsted caused many women’s lives to be saved. We should respect those who have gone before us and learn from their work, whilst at the same time be willing to question and improve upon it. We need to guard ourselves from repeating mindlessly that which we have been taught, without seeking to develop it. Much has changed since Halsted boldly stated, “Tumours should never be harpooned, nor should pieces ever be excised from malignant tumors for diagnostic purposes.” [7] This may seem strange considering how we now utilise biopsies, although in years to come the flaws in our own thoughts and practices will be exposed.

Halsted was innovative, bringing discoveries to his time, and he will always hold an important role in surgical history. The French philosopher Gaston Bachelard displayed wisdom in saying “the characteristic of scientific progress is our knowing that we did not know”. It should be added that scientific progress comes through our knowing there is much we still do not know, and it is up to us to seek the answers.

Conflict of interest

None declared.

Correspondence

R Young: rebeccayoung07@gmail.com

References

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[2] Penninton D. Breast reconstruction after mastectomy: current state of the art [Review]. ANZ J Surg. 2005;75(6):454-8.

[3] Rankin J. William Stewart Halsted: a lecture by Dr Peter D. Olch. Ann Surg. 2006;243(3): 418-25.

[4] Roberts C. H.L Mencken and the four doctors: Osler, Halsted, Welch, and Kelly. Proc Bayl Univ Med Cent. 2010;23(4):377-88.

[5] Lathan S. Dr Halsted at Hopkins and at High Hampton. Proc Bayl Univ Med Cent. 2010;23(1):33-7.

[6] Halsted W. The results of operations for the care of cancer of the breast performed at the Johns Hopkins hospital from June, 1889, to January, 1894. Ann Surg. 1894;20(5):497-555.

[7] Halsted W. I. A clinical and histological study of certain adenocarcinomata of the breast: and a brief consideration of the supraclavicular operation and of the results of operations for cancer of the breast from 1889 to 1898 at the Johns Hopkins Hospital. Ann Surg. 1898;28(5):557-76.

[8] Veronesi M, Cascinelli N, Mariani L, Greco M, Saccozzi R, Lunini A et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227-32.

[9] Feigenberg Z, Zer M, Dintsman M. Comparison of postoperative complications following radical and modified radical mastectomy. World J Surg. 1977; 1(2): 207-10.

[10] Uroskie T, Colen L. History of breast reconstruction. Semin Plast Surg. 2004;18(2):65-9.

[11] Association of Breast Surgery at BASO BAPRAS and the Training Interface Group in Breast Surgery. Oncoplastic breast surgery – a guide to good practice. EJSO. 2007;33:S1-23.

[12] Bland C. The Halsted mastectomy: present illness and past history. West J Med. 1981;134(6):549-55.

[13] Veronesi U. Rationale and indications for limited surgery in breast cancer: current data. 1987;11(4):493-8.

[14] Fisher B, Jeong J, Anderson S, Bryant J, Fisher E, Wolmar N. Twenty-five-year follw-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;346:567-75.

[15] Tanis P, Nieweg O, Olmos R, Rutgers E, Kroon B. History of sentinel node and validation of the technique. Breast Cancer Res. 2001;3(2):109-12.

[16] Giuliano A, Kirgan D, Guenther J, Morton D. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391-8.

[17] Taylor M, Perez C, Halverson K, Kuske R, Philpott G, Garcia D et al. Factors influencing cosmetic results after conservation therapy for breast cancer. Int J Radiat Oncol Biol Phys. 1995;31(4):753-64.

[18] Rose M, Olivotto I, Cady B, et al. Conservative surgery and radiation therapy for early breast cancer: long-term cosmetic results. Arch Surg. 1989;124(2):153-7.

[19] Clough K, Lewis J, Couturand B, Fitoussi A, Nos C, Falcou M. Oncoplastic techniques allow extensive resections for breast-conserving therapy of breast carcinomas. Ann Surg. 2003;237(1):26-34.

[20] Clough K, Kaufman G, Nos C, Buccimazza I, Sarfati I. Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery. Ann Surg. 2010;17(5):1375-91.

[21] Suarez J, Arthur D, Woodward W, Kuerer H. Breast preservation in patients with local recurrence after breast-conserving therapy. Curr Breast Cancer Rep. 2011;3(2):88-96.

[22] Rozen W, Ashton M, Taylor G. Defining the role for autologous breast reconstruction after mastectomy: social and oncologic implications. Clin Breast Cancer. 2008;8(2):134-42.

[23] Czerny V. Plastic replacement of the breast with a lipoma. Chir Kong Verhandl. 1895;2:216.

[24] Tanzini I. Spora il mio nuova processo di amputazione della mammella. Riforma Medica. 1906;22:757.

[25] Teimourian B, Adham M. Louis Ombredanne and the origin of muscle flap use for immediate breast mount reconstruction. Plast Recontr Surg. 1983;72:907-10.

[26] Cronin T, Gerow F. Augmentation mammoplasty: a new “natural feel” prosthesis. Transections of the third international congress of plastic surgery, Amsterdam. Excerpta Medica. 1964;66:41-9.

[27] Snyderman R, Guthrie R. Reconstruction of the female breast following radical mastectomy. Plast Reconstr Surg. 1971;47:565-7.

[28] Radovan C. Breast reconstruction after mastectomy using the temporary expander. Plast Reconstr Surg. 1982:69:195-208.

[29] Lanitis S, Tekkis P, Sgourakis G, Dimopoulos N, Al Mufti R, Hadjiminas D. Comparison of skin-sparing mastectomy versus non-skin-sparing mastectomy for breast cancer: a meta-analysis of observational studies. Ann Surg. 2010;251(4):632-9.

[30] Becker H. Breast reconstruction using an inflatable breast implant with detachable reservoir. Plast Reconst Surg. 1984;73:678-83.

[31] Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360:790-800.

[32] Agarwal G, Ramakant P, Forgach E, Rendón J, Chaparro J, Basurto C et al. Breast cancer care in developing countries. World J Surg. 2009;33(10):2069-76.

[33] Saini K, Taylor C, Ramirez A, Palmieri C, Gunnarsson U, Schmoll H et al. Role of the multidisciplinary team in breast cancer management: results from a large international survey involving 39 countries. Ann Onc. 2012;23:853-9.