The world we live in

Among the great mysteries of human existence, our uncertain relationship with our environment has been a constant source of puzzlement. In the days of the flat earth, when gods and planets needed constant placation and sacrifice lest the food supply fail and fertility fall, surging infections were thought to be a further manifestation of divine displeasure — something that the deities inflicted upon the people (demos) from above (epi) to chasten and punish. Yet the Old Testament book of Leviticus shows that, thousands of years ago, the need to quarantine people with rashes or swellings “like the plague of leprosy” was recognised (Leviticus 13: 2–5), implying that humans understood from early on that they had a measure of control over infective afflictions.

The path from primitive ignorance and fear to the understanding of the microbiological cause of infection is, as the cliche runs, history. Nevertheless, we continue to fear uncontrolled epidemics, despite our heavy investment in technology to hold them at bay.

Battling the threats

At the beginning of 2003, during the early phases of the severe acute respiratory syndrome (SARS) epidemic, I saw lights burning in the windows of Ian Lipkin’s microbiology laboratory at Columbia University, close to where I was working at the time, for 24 hours every day during the race to sequence the genome of the virus responsible. By May, the 29 751-base genome of the Tor2 isolate had been sequenced in British Columbia and published in Science.1 Fortunately, although SARS was a serious illness, as classical epidemiological data were assembled we recognised that it had low infectivity. We had come to know the enemy — quickly and in fastidious detail — yet we still needed traditional methods to prevent its spread.

Infection retains its character of surprise. Who would have guessed the story of Helicobacter pylori and peptic ulcers? As an intern in 1966–1967, peptic ulcer meant antacids, stress and socioeconomic status, vagotomies, pyloroplasties and heroic surgery for life-threatening haematemesis. What other disorders — cancer, coronary disease — may have an infective element in their aetiology? And, like the global financial crisis of 2008, the Ebola epidemic of 2013 caught us off guard. It also reminded us of how critical the social environment and poverty, in particular, are to the formation of modern infective epidemics.

Complex relationships

In recent years, dramatic developments in our exploration of the universe of infection have led us to the human microbiome — the “organ” that has 10 times as many cells as does the whole of the rest of the human body — that inhabits our gut, skin and other surface tissues, and about which new knowledge is coming to us daily. A 2012 Spanish study described a changing microbiome profile in human breast milk over the months after birth that involved over 700 species of microorganisms.2

I had a glimpse of the importance of the human microbiome in 1968 when working at Baiyer River in the western highlands of Papua New Guinea. We were visited by Eben Hipsley, a nutrition scientist from Canberra, who had an interest in understanding how the local Enga people, naturally muscular and fit, kept their metabolism going without eating much more than sweet potato.3 What about essential amino acids? In private conversation, Eben conjectured that their gut flora generated the molecules missing from this people’s natural diet. Today’s experts in this field presumably have a much better idea of Papua New Guinean nutrition, but Hipsley respected what he knew, even then, of the human microbiome. Contemporary experts now agree that while human microbiota do not fix atmospheric nitrogen, they can upgrade dietary nitrogen-containing compounds into essential amino acids.4

Together, we triumph

In terms of infection control, the global response to HIV has been an astounding exercise that combined technology, preventive science, biological insight, social understanding, philanthropy and dogged global political action. This, together with the GAVI Alliance (made up of such heavyweights as the World Health Organization, UNICEF, the World Bank, the Bill & Melinda Gates Foundation and donor countries), the Global Fund to Fight AIDS, Tuberculosis and Malaria, and the elimination of smallpox, should surely give heart to those who doubt the value of medical research and action. Rather than lamenting what we can’t do, these achievements signal what amazing things we can do together when we try.

Changes to the format of the MJA

Here at the MJA, our centenary celebrations of 2014 are over and we are turning to what lies ahead.

By now you will have noticed that recent issues of the MJA have incorporated changes to the design that are intended to make it modern and easier to read. We are making these changes to the format of the Journal in response to surveys of readers and observation of international best practice in medical journal publication.

Among the changes we have already introduced are the addition of colour-coded article types and page numbers, removal of the reference lists from the print edition (these are published online), and an increase in visual impact through greater use of images.

Further changes are also in the works. From July this year, the MJA proposes to publish all research articles fully online, with a summary page published in print. The purpose of the one-page summary is to convey the main points of the research to readers in an engaging way. Summaries will be requested from contributors whose manuscripts proceed past the initial review stage. Further details on the requirements of research summary pages are available in our instructions to authors: https://www.mja.com.au/journal/mja-instructions-authors-types-articles-published-mja#Research.

We also propose to make several small changes to our editorial format for articles other than original research. These changes are intended to make access to the contents of the Journal easier both in print and online.

We will keep you informed of these proposals and hope that you will let us know how well they serve your needs as a reader and contributor.

Local acquisition and nosocomial transmission of Klebsiella pneumoniae harbouring the blaNDM-1 gene in Australia

The emergence of carbapenem-resistant Enterobacteriaceae constitutes a critical global issue. Isolates harbouring the metallo-β-lactamase gene blaNDM-1 have few available treatment options. We report a case of an Australian adult with a locally acquired, community-onset blaNDM-1 Klebsiella pneumoniae infection and likely nosocomial transmission to another patient.

Clinical records

Patient A, a 68-year-old Australian-born woman living with her husband and son, had never travelled overseas and had no known contact with overseas visitors. Her past history included chronic bilateral lymphoedema with recurrent lower limb cellulitis, requiring multiple previous hospital admissions and home nursing care. She presented with septic shock and right leg erythema surrounding a 10 × 10 cm ulcer near the right lateral malleolus. Magnetic resonance imaging showed bony oedema and enhancement in the lateral malleolus, suggestive of osteomyelitis. Pseudomonas aeruginosa was isolated from blood cultures. A tissue biopsy from the overlying ulcer cultured P. aeruginosa, non-multiresistant methicillin-resistant Staphylococcus aureus (NORSA), and carbapenem-resistant Klebsiella pneumoniae, resistant to all first-line antimicrobials tested and susceptible to only colistin and fosfomycin.

She was given intravenous ceftazidime and vancomycin for treatment of P. aeruginosa and NORSA infection. After 6 weeks of treatment, the ulcer was not healing, and treatment for the carbapenemase-producing K. pneumoniae was commenced with intravenous colistin methanosulfonate (120 mg colistin base activity 12-hourly). Colistin was ceased after 3 weeks owing to acute kidney injury, and oral fosfomycin (3 g every 3 days) was administered for a further 6 weeks, in addition to oral ciprofloxacin and rifampicin for ongoing treatment of NORSA and P. aeruginosa infection. Since the cessation of her antibiotics, she has not required further antibiotic treatment of her ulcers.

Patient B, a 35-year-old Australian-born man with no history of overseas travel, was admitted with bilateral thigh cellulitis and septic shock. He had bilateral thigh debridement, with no evidence of necrotising fasciitis. Methicillin-susceptible S. aureus (MSSA) was isolated from multiple blood cultures. MSSA and Serratia liquefaciens were isolated from a thigh wound swab culture. Transthoracic echocardiogram revealed a left ventricular thrombus. He was commenced on intravenous flucloxacillin and ciprofloxacin. Two weeks after admission, further surgical samples from his thigh wounds cultured carbapenem-resistant K. pneumoniae, with similar antimicrobial susceptibility phenotype to Patient A. The isolate was deemed to be colonising the wound only, and no antimicrobials were commenced for treatment.

Both K. pneumoniae isolates demonstrated carbapenemase activity using the Carba NP assay.1 Molecular tests using polymerase chain reaction and sequencing for carbapenemase, extended-spectrum β-lactamase, plasmid-mediated AmpC β-lactamase and 16S ribosomal RNA methylase genes were performed as described elsewhere.2 The metallo-β-lactamase gene blaNDM-1 was detected in both isolates, in addition to blaCTX-M-15 and 16S ribosomal RNA methylases (armA and rmtB), which confer resistance to aminoglycosides, including amikacin. The relatedness of isolates was determined by semi-automated repetitive sequence-based polymerase chain reaction using a DiversiLab Klebsiella kit (bioMérieux). This analysis showed a > 95% genetic similarity between the two isolates. Further, the isolates were genetically distinct from two blaNDM-1-harbouring isolates that we isolated previously in patients with a history of overseas travel.

Patients A and B were admitted in December 2013 to a high dependency unit (HDU) — a four-bed area separated by curtains. They were one bed apart for 5 days before being moved adjacent to each other for 1 day, with Patient B occupying the bed cubicle space formerly occupied by Patient A for a further 5 days. The carbapenem-resistant K. pneumoniae was first identified in Patient A in the HDU, and 2 weeks later was isolated from Patient B.

After detection of the carbapenem-resistant K. pneumoniae, strict contact precautions were implemented. Environmental cleaning of the four-bed HDU and other rooms occupied by Patients A and B was undertaken with microfibre and steam cleaning, which has been shown to be an effective cleaning method.3 An exposure investigation was conducted, with environmental sampling and screening rectal swabs collected from all direct patient contacts of Patients A and B inoculated on chromogenic selective media. No other carbapenem-resistant organisms containing blaNDM-1 were isolated from clinical, screening or environmental samples.

Discussion

The metallo-β-lactamase gene blaNDM-1 was first described in a patient hospitalised in Sweden after travel to India in 20084 and subsequently identified in a series of patients in the United Kingdom, many of whom had travelled to the Indian subcontinent.5 There have been documented cases of infection with imported blaNDM-1-containing bacteria in Australia.6–10 These carbapenem-resistant bacteria are challenging to treat, as available treatment options are often limited to infrequently used drugs such as colistin, fosfomycin and tigecycline.

The case of Patient A has significant public health ramifications as the first detection of carbapenem-resistant blaNDM-1-harbouring K. pneumoniae infection locally acquired in Australia, independent of international travel or documented contact with a traveller. The case suggests that there may be more cases of blaNDM-1-harbouring bacteria in our community than previously suspected. We hypothesise that this carbapenem-resistant Enterobacteriaceae isolate was acquired after transmission from an unidentified carrier of blaNDM-1, possibly during previous hospital admissions or receipt of home nursing care.

The transmission from Patient A to Patient B may have occurred via a number of mechanisms. First, environmental contamination may have contributed, given that both patients shared the same bed area at different times. We previously reported an outbreak of carbapenem-resistant Enterobacteriaceae harbouring the metallo-β-lactamase gene blaIMP-4, associated with contaminated sinks in an intensive care unit; in that case, no carbapenem-resistant organisms containing blaNDM-1 were isolated from environmental samples.11 The second possible contributing factor for transmission is lapses in infection control practices by health care staff, which emphasises the importance of adhering to standard precautions such as hand hygiene.12

These cases highlight the evolving Australian epidemiology of multidrug-resistant organisms, particularly bacteria harbouring blaNDM-1. Such resistance is no longer exclusively associated with obvious international travel. There is an increasing need for effective antimicrobial stewardship and infection control measures to prevent potential future nosocomial spread of these organisms. In addition, further research and surveillance is needed in monitoring these local isolates to identify potential risk factors for local acquisition and any reservoirs within the Australian health system and community.

The serious challenge of medical research

Imagination is more important than knowledge. For knowledge is limited, whereas imagination embraces the entire world, stimulating progress, giving birth to evolution. It is, strictly speaking, a real factor in scientific research.

Albert Einstein

Two emails that landed on my computer screen recently gave clues to the amazing pace and reach of medical research. Both advertised conferences: one planned for Boston in July, and the other in San Diego in March this year.

The Boston meeting, entitled the Organ-on-a-Chip World Congress, is rather breathlessly described as concerning “assemblies of cell clusters using microfluidics that mimic in vivo organ structure”. Technology options to be reviewed at the congress resemble a fast-food menu — Lung-on-a-Chip, Brain-on-a-Chip and Gut-on-a-Chip.

The San Diego conference, Biomarker Summit 2015, will consider “all aspects of the biomarker and diagnostic development process from discovery to translation to commercialization”, with topics covering “big data analytics and management, regulatory and reimbursement trends, companion diagnostics development, and much more”.

In contemplating the future of medical research in Australia, the international context, typified by what lies behind these two meetings, is critical. Two features stand out.

Biology — make way for IT

First, wherever you look, the massive contributions to medical research by non-biological sciences are paramount. Craig Venter, a gene scientist who sequenced the human genome, states in his book Life at the speed of light that genetic research and information science are so interwoven as to be inseparable. His book takes its title from his suggestion that if a sophisticated probe found life in deep water below the surface of Mars, an on-board sequencer could decipher and digitise its genome and radio the code at the speed of light to a laboratory on earth (presumably his), to be reconstituted to build a Martian organism.

In neuroscience also, technology not thought of as medical is now thoroughly integrated with biology. Workers studying changes in brain function as they relate to behaviour depend heavily on such technology. Denis Le Bihan, a French neuroscientist and major inventor of imaging techniques, extols the contribution of magnetic resonance imaging to our understanding of brain function in his new book Looking inside the brain.

Neuroscience leapt forward in the 1970s when computerised neuroimaging became available to the research and clinical communities. Physics underpinned the development of the electroencephalograph. New levels of neurological and psychiatric understanding are leading to new therapies, such as deep brain stimulation. Depression, Bihan suggests, may soon be seen as a feature of many abnormalities, just as the once-solid disease called “fever” broke apart when its multiple causes were found. In all these discoveries, engineering, information science and mathematics are deeply embedded.

Medical research is good economics

Second, we need to see research much more clearly, as others are doing, as a major economic opportunity for government and the private sector alike. The two conferences I mentioned are almost entirely private sector-sponsored. Medical research is an intellectual industry. Smart, future-oriented economic thinking would be seeking ways to position Australia at the head of the pack. Pedalling happily in the Alpine sunshine at the back of the peloton is just plain dumb economics. The oft-repeated (appalling) mantra that we are “punching above our weight”, based on publications, seriously mistakes past achievement for future opportunity. Research is a fierce competition. Winners do well. They need expensive support teams.

How is it that our major project grants scheme — the National Health and Medical Research Council — supports fewer than one in five applicants? If one in five missed out, the arrangements would be credible.

It is among the project grants that bright, risky and imaginative ideas are often found. Imaginative questions are the essence of research: yes, it does require high-tech and massive investment to prosper, but if the intellectual electricity is missing, the wheels do not turn. Were the Medicare levy raised by 0.5%, the $3 billion raised each year could be applied to medical research — an amount much larger, and more equitably procured, than was to be raised through the proposed copayment for Medicare services. There would be no sitting and waiting for a future fund to bear fruit.

A big increase in our present fund also makes investment sense, so that we can more appropriately match the achievements of our economic peers and grow the world’s best research community, fit for future purpose, from our large talent pool. Channelling Henry Ford, we may say that what’s good for research is good for Australia.

While no one should promise that medical research will find a cure for cancer or Alzheimer’s disease, at least not in the next few years, it is certain that we will not find a cure any other way. Fortunately we live in a gilded age of science, and all of it — not just the disciplines classically seen as medical — has a contribution to make to medical achievement. It requires political and private enterprise and vision to enable it, through generous, imaginative funding.

[Comment] Strategic science with policy impact

Evidence-based policy making is an important aspirational goal, but only a small proportion of research has the policy impact it might have. Most researchers are not trained to create policy impact from their work, engagement with policy makers is not encouraged or rewarded in most settings, and the communication of scientific findings occurs within the academic community but rarely outside it. There are exceptions, but little is done to systematically link scholarship to policy.

[Perspectives] Christina Roberto: taking a broad view on combating obesity

PEACH Lab—the Psychology of Eating and Consumer Health—is the intriguingly named research centre which is home to the work of Christina Roberto, a key figure behind a new Lancet Series on obesity. “There has been limited and patchy progress on tackling obesity globally”, says Roberto, who is Assistant Professor of Social and Behavioural Sciences and Nutrition at the Harvard T H Chan School of Public Health.

Peer review: maintaining trust in research funding decisions

Ensuring that the peer-review process adapts as medical research changes

Researchers in Australia have recently criticised peer review of applications for grant funding, arguing that the process involves too much work, is too arbitrary and is too conservative in identifying the best grants.1

These criticisms need to be addressed, but they must also be balanced by other considerations, especially the interests of the wider community.

Public research funding bodies like the National Health and Medical Research Council (NHMRC) and the Australian Research Council rely on peer review when deciding who and what to fund. Because Australians’ taxes pay for the funding, funders have responsibilities to ensure that peer review is able to identify the most valuable research to fund, and to do so fairly, free from bias and self-interest.

The NHMRC’s funding decisions depend almost entirely on researchers’ peer review. It is remarkable that the public trusts us researchers with towards a billion dollars a year of their money, and we have a responsibility to maintain this trust.

Peer reviewing is an essential part of being a scientist, and we can expect to spend a sizeable amount of our time providing reviews of other researchers’ applications for funding (and publishing). It is a type of mutual obligation — participation in the peer-review process is our reciprocal duty towards other researchers.

To maintain public and researcher trust, it is essential that processes are fair and provide applicants natural justice. There is never enough money to fund all worthwhile research. Therefore, it is important to ensure that the playing field is level. As far as possible, applicants need to be aware of the assessment criteria, and be given a chance to respond to the views of reviewers, including possible misconceptions or errors. Over a decade ago, the NHMRC introduced specific criteria for the assessment of applications and assigned specific weighting to each of these. Applicants’ understanding of what they will be assessed on also allows them to write their applications accordingly — a general principle now generally agreed on in the San Francisco declaration on research assessment (http://www.ascb.org/dora-old/files/SFDeclarationFINAL.pdf)

Peer review is a human activity, so any two researchers are likely to have different views. For funders, it is essential to bring as many experts as possible to the review and to ensure that interests (scientific or material) are transparent and taken into account. Peer review is inherently tied up with the values and knowledge of the individuals involved. It follows that it is important to have knowledgeable and ethical researchers involved. Peer review can never be reduced to a simple number that does not require human judgement.

Humans do err in their judgements, and there are few researchers who would be willing to leave a decision on their application to a “lottery”, a political process or the decision of a single superior (eg, a deputy vice-chancellor or institute director). In the 21st century, few researchers will tolerate “I know a good grant when I see one — just trust me”.

We can always do better. Funders need to constantly assess their processes and the outcomes. More training and mentoring in quality peer review would also help. Most of us learn about peer review informally as early career researchers through departmental and research group seminars, and as we begin to be asked to assess grants and papers submitted for publication.

Can peer review ever be a precise instrument? No, but we should strive to make it as good as possible, in order to identify the best research to fund, fairly and without bias.

Health and medical research grows and changes. It is becoming more diverse, complex, multidisciplinary and collaborative across institutions and around the world. We all need to ensure that the peer-review process adapts and evolves to meet the challenges that these changes are bringing.

Medical cannabis: time for clear thinking

Australia is behind the times on the medical use of cannabis

The debate about the medical use of cannabis in Australia has become confused with the proposal for a formal clinical trial instead of proceeding to legislation in New South Wales, the Australian Capital Territory and Victoria. Debates about prohibition of cannabis have a long history,1 as has the proposal for medical cannabis in Australia.2 Politicians are nervous about being “soft on drugs”, especially before an election. The clinical trial proposed, if successful, presumes that cannabis would then be approved and regulated as a pharmaceutical substance.

We need to be across the facts and options. Cannabis can never be a pharmaceutical agent in the usual sense for medical prescription, as it contains a variety of components of variable potency and actions, depending on its origin, preparation and route of administration. Consequently, cannabis has variable effects in individuals. It will not be possible to determine universally safe dosage of cannabis for individuals based on a clinical trial.

Extreme views in the debate about any form of cannabis decriminalisation are advanced with almost religious fervour. On the one hand, some assert that cannabis is a dangerous, highly addictive drug which causes schizophrenia, and that any move to relax prohibition would be a disaster. This view defies published evidence. On the other hand are those who have used cannabis for years, swearing it causes no trouble. They see prohibition as a totally inappropriate curb on individual freedom.

Facts about cannabis

The assertion that cannabis is highly addictive ignores firm evidence. The most authoritative review comparing addictiveness of drugs rates physical dependence on a scale of 0–3.3 Heroin is ranked 3; tobacco, barbiturates and benzodiazepines, 1.8; alcohol, 1.6; and cannabis, 0.8. Cannabis may, of course, be a pathway to more addictive drugs if obtained from illegal sources that also offer powerful alternatives.

The view that cannabis carries no risk likewise ignores much published evidence.4 Recent Australian and New Zealand longitudinal studies show significant social, behavioural, educational and mental problems with frequent use of cannabis by young people (aged 15–25 years). Psychosis occurred more frequently following long-term heavy use than among non-users, but no schizophrenia was noted in this study.5 A recent review of the evidence implicating cannabis in the development of schizophrenia found only that it can accelerate its expression at an earlier age and may aggravate existing schizophrenia. Of course, non-users also develop schizophrenia.6 Others have identified heavy cannabis use in the young as a possible factor in later psychosis, without specifying schizophrenia.7

Australians, together with citizens in the United States and New Zealand, are the world’s greatest users of cannabis per head of population.8 Prohibition has failed to prevent widespread use and young people report that they can readily access it.9 Young people need to be strongly dissuaded, on health grounds, from frequent or even regular use of cannabis, but this has little relevance to cannabis used for medical purposes or the debate surrounding it. Potential medical users are often, for example, in the later stage of a battle with painful cancer, finding problems with morphine, other analgesics and nausea with chemotherapy. Others seek relief from painful conditions such as muscle spasm in multiple sclerosis. Cannabis is believed to reduce seizures in Dravet syndrome, a rare genetic myoclonic epileptic encephalopathy beginning in infancy.10 Most parents of affected children (84%) report much lessened frequency or abolition of seizures with medical cannabis. They should have continuing access to it until trials using purified cannabidiol (CBD), believed to be the active component for these children, provide a superior agent.

We are behind the times on medical cannabis. Currently, 23 states in the US have legalised use of cannabis for medical conditions, as has Canada since 2001. Other countries approving it include Israel, Holland and the Czech Republic. Portugal, in 2001, removed penalties for personal possession and use of all illicit drugs, but with rigorous administrative processes to handle problem use. Eliminating prohibition is not a disaster if there are sensible processes to control drug-related harms.11

An Australian and US study found that removal of legal action and possible imprisonment for possession and use makes no difference to the patterns of use of cannabis.12 World Health Organization mental health surveys of 17 countries found that “countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones”.13 There is no rational basis for the view that weakening prohibition to permit use for medical conditions would lead to a surge in general use.

Cannabis has at least two important active elements: δ-9-tetrahydrocannabinol (THC) and CBD. The former is responsible for the high of intense comfort and pleasure when presented to the brain in sufficient quantum. Its presence is greatly enhanced by heating marijuana above 170°C, as in a bong, converting the inactive precursor THC-A to THC. THC infused at high dose can produce a powerful euphoria but also hallucinations and other psychotic effects in some normal individuals, followed by complete recovery.14 CBD, on the other hand, does not give a high but has other effects including suppression of nausea and pain. It counteracts some of the effects of THC.15 The plant Cannabis sativa has more than 100 alkaloids with potential to influence the cannabis receptors CB1 and CB2, which respond to normal cannabinoids.16

Response to cannabis varies from person to person, partly due to genetic variation among users.17 The content of THC and CBA varies among different strains of marijuana. Some users vary the type of plant they use to benefit from these different effects.

What would a clinical trial entail?

Cannabis as such cannot be subjected to a double-blind clinical trial. Participants would have to agree to be treated with it, hoping to gain relief from distressing pain or nausea. Each would become aware whether they are receiving cannabis or a placebo. Dose would have to be adjusted for each individual. Any trial would use cannabis with multiple active constituents, varying with the source of marijuana used and its preparation.

If a person in the late stages of painful cancer seeks the euphoria of THC, why should they not have it? They must have a right to withdraw from a trial if it does not suit them. Participants in the control group may demand to transfer to the active arm on seeing others feeling better. Cannabis should supplement morphine for pain as necessary, not replace it.

Are there barriers in principles of medical practice?

There may be medicolegal issues if a medical practitioner prescribes a preparation of unquantified potency or with an incomplete description of its constituents and without full knowledge of side effects and their extent. But this has not proved to be a problem in those US states where the patient makes the choice to use cannabis following a medical consultation. A recent readership survey conducted by the New England Journal of Medicine sought comment on a published case report of a cancer patient where a senior psychiatrist and a pain management specialist had both recommended against use of cannabis. Seventy-six per cent of respondents from several countries responded that they would recommend use of cannabis in such a case.18 Medical marijuana is now widely used. A recent US study found that the states with medical cannabis use over 10 years had a lower death rate from opioid overdose than those without.19

Why not go ahead with legislative approval?

The real question is whether a person who is suffering pain and distress can access cannabis on their own initiative, following medical consultation as to their symptoms. They can access other herbal remedies from authorised providers such as health food stores or a pharmacist. If legislation permits sale to people suffering from a condition diagnosed by a doctor and scheduled in legislation, there should be no problem with provision of cannabis by this route without waiting for completion of a clinical trial. This is especially the case with Dravet syndrome patients where a formal clinical trial with a proprietary CBD concentrate20 may take several years to complete.

We should ensure that cannabis is provided only to approved users who should be registered. As there is no legal supplier, users should have permission to grow their own plants — up to 10 at any one time — but be forbidden from selling their product. Any proposal for commercial production should be subject to strict control, with analysis of THC, THC-A and CBD content by a government toxicology laboratory for both cannabis oil and the leaf product. Venues for sale, presumably pharmacies or health food shops, should be registered. People aged between 15 and 25 years should be excluded as recipients, except where it is provided specifically for a cause covered by legislation. The legislation should also make cannabis available for medical research.

In summary, use of cannabis should be decided by the patient, following medical advice about the condition from which they seek relief, with patients being registered under state legislation. If there is to be a nationally approved trial, it should be one of documenting clinical experience from cannabis use under state legislation of the kind foreshadowed by recently elected Victorian Premier Daniel Andrews.21

Enabling the success of academic health science centres in Australia: where is the leadership?

Lack of policy development hinders the effective integration of research, education and health care delivery

The expanding health care demands of our community require that our health system have an expanding knowledge base, enhanced capability, greater process efficiency and more targeted application of clinical interventions. The search for new groundbreaking discoveries should continue unabated (for example, in replicating the success of statins in ameliorating coronary heart disease or antiretroviral therapy in controlling HIV infection). However, there is an equally important, immediate and ongoing daily need for all patients to receive better, safer and more efficient care from highly competent health professionals using existing knowledge and resources. This responsibility must be shared between health administrators, front-line health professionals, and academic teachers and researchers.

In recognition of this shared responsibility, at least four academic health science centres (AHSCs) have been established in Australia in the past 5 years. They comprise partnerships or collaborations between universities and their affiliated research institutes and health service organisations.

There is no universally agreed definition of an AHSC, but most are alliances of geographically co-located entities, with varying descriptions of what they actually do or hope to achieve. However, all AHSCs are committed to a tripartite mission of advancing research, education, and patient care. This mission presents challenges for AHSCs worldwide in responding to demands for high-value, patient-centred care and improved population health. Historically, the research stakeholders within AHSCs have attracted funding primarily to conduct basic research and biomedical studies aimed at new diagnostic and therapeutic discoveries, with less emphasis on education, patient care (especially primary care and preventive medicine), and health services research.1 However, this is likely to change as AHSCs realise they must match their pre-eminence in the science of discoveries with equal commitment to translational and implementation science focused on health system improvement.2 Can AHSCs truly claim to excel in scientific discovery if they are not researching ways of making clinical services more reliably excellent? Can they truly claim to teach high-quality medicine without consistently providing high-quality care? The AHSC needs to be defined as a centre of learning committed to improving health and health care by advancing, applying and disseminating knowledge through a learning health system.

Defining stakeholder roles and functions

Putting this ubiquitous aim of high-quality care for all into operation is the prime responsibility of health departments and health services, and is exacted by multiple key performance indicators (KPIs) and contractual obligations applied to their staff. Universities and research institutes are also subject to a regulatory system, but one that involves different performance measures centred on research output and academic excellence. These different objectives constrain the development of integrated health, education and research partnerships, which need to share a set of common objectives, incentivised by funding arrangements that all parties in the alliance can sign up to.

Such convergence is possible and necessary. In exploring new and better models of care, managers are seeking front-line clinician–researchers with leadership skills who can assist in the process. Engaging practising health professionals in the science of health service innovation presents a challenge. Specialty colleges and other professional bodies need to view and endorse AHSCs as one means of engaging their clinician constituency in health system improvement and the acquisition of requisite skills.3 Front-line consumers of health care must also be involved in determining priorities for research and service delivery.

In turn, senior government representatives and policymakers must show leadership in endorsing and resourcing ASHCs as vehicles for drawing together, with appropriate balance, all of the endeavours directed towards improving health care for, and the health of, the community. Health service managers need to make their services more research-friendly by actively facilitating research governance, ethics approvals, participant access and recruitment, and data collection systems.

The success of AHSCs as vehicles underpinning learning health systems requires structural alignment and functional integration of research, education and clinical service delivery. Accountability for each of these three elements, which are currently held by different agencies (traditionally universities and research institutes for research, teaching hospitals for education, and hospitals and health services, including primary care, for clinical services), must be brought together under one integrated learning health framework. This will not be easy. It requires both bottom-up leadership by local academic and clinical leaders and top-down leadership from government departments, statutory bodies and health service administrations. The boards of AHSCs must overcome the current physical, financial, administrative, professional, legal and historical factors that currently constrain research, education and service excellence within the individual partnering organisations. The operations of these new partnerships must be aligned so that new and better ideas and technologies that solve priority population health problems can be introduced more quickly, efficiently and effectively.

Encouragingly, there is evidence that the need for such alignment is recognised and is beginning to happen within AHSCs in the United States,4 United Kingdom5 and Canada,6 driven in no small measure by government policies, such as the Affordable Care Act 2010 in the US, and the Health and Social Act 2012 in the UK. In particular, AHSCs in the UK are now being surrounded by academic health science networks to ensure broader implementation of knowledge into patient care.5 In Australia, calls for recognition of the value of university teaching hospitals7 have drawn attention to our nation lagging behind international developments in integrating science and clinical service delivery,8 and have advocated for government action in developing AHSCs.

The research community perspective

In late 2010, the National Health and Medical Research Council (NHMRC) released a discussion paper that proposed to “invite consortia of universities, hospitals and medical research institutes to apply for recognition for excellence in research and research translation”.9 The NHMRC proposed that such centres be designated “Advanced Health Research Centres”. This descriptor was criticised by deans from the Group of Eight Universities8 for its eschewing of academia. The apparent tight alignment of “excellence” with basic science research, disproportionately rewarded by the NHMRC project grants system,1 also constrained any significant shift of academic mindsets towards applied clinical research and implementation of knowledge. This shortcoming was further profiled in the McKeon Review of health and medical research (HMR) in Australia,10 commissioned by the federal government. That review involved a wide diversity of stakeholders, and it proposed “an overarching message . . . [about the] lack of a sufficiently strong connection between HMR and the delivery of healthcare services”.10 It highlighted the need for an academic leadership body, as well as financial commitment and closer integration of research centres, if research was to be better embedded in the health care system. It also recognised the need for more commercialisation of research in parallel with translating evidence into practice. The review was released in February 2013, but the federal government is yet to formulate a policy and a structure for meeting these identified needs.

This shift towards closer integration between those who generate and those who use research has continued with the establishment of an NHMRC research translation faculty and, more recently, calls for submissions from academic and health care precincts to be recognised as Advanced Health Research and Translation Centres (AHRTCs).11 This new concept places yet more emphasis on how the scientific output of AHRTCs directly influences clinical practice and teaching, health care policies, and population health outcomes, both locally and more broadly.

Uniting for a common cause

We acknowledge that the prevailing uncertainties in the absence of a national plan for AHSCs may make whole-hearted commitment to comprehensive integration of academic and service organisations more difficult. Universities and biomedical research institutes are concerned that some of their research funding may be diverted to health service delivery, while health services have concerns that the reverse could occur, especially given the potentially large scope of clinical and health services research that will be required to drive evidence implementation and innovation across the entire health care system.

This uncertainty impedes a concerted effort to bring applied clinical and health services research into both mainstream academia and service delivery, as evidenced by the relatively few centres of clinical effectiveness or health service evaluation in this country. Although the science of implementation is receiving increasing attention internationally,12 maximal benefit from clinical research, knowledge translation and service innovation will only be realised by collaborative academic–service partnerships that cover the whole spectrum, from basic science to front-line patient care. Within such partnerships, the mindsets of all agencies and individuals involved, including those of practising clinicians, must converge on creating learning health care systems that aspire to deliver the best possible health care within declared financial constraints. Strategies for facilitating such convergence in our AHSC13 are provided in the Appendix.

The mission for AHSCs and AHRTCs is to serve as vehicles for integrating academia and service delivery for the benefits of the community. Whether they succeed will depend on whether the partnering organisations within them, government departments, the NHMRC and the health professions believe in their worth and are prepared to openly support them with the required resources and governance frameworks. We challenge government and all key stakeholders to step forward and develop policies for ensuring their creativity, relevance, and sustainability.

[Comment] The spirit of Mexico: a decade on

November, 2014, marks the 10th anniversary of the Mexico Ministerial Summit on Health Research, attended by 20 ministers of health and delegations from 51 countries. Convened by the Government of Mexico, the Global Forum for Health Research, and WHO, the Summit endorsed the role of knowledge for better health1 through the Mexico Statement2 and a resolution passed at the World Health Assembly in 2005.3 Initially driven by the strong personal commitment and vision of WHO’s then Director-General, the late Lee Jong-wook, much progress has been made in the past decade; however, substantial challenges remain.