A 25-year-old woman presented with progressively worsening shortness of breath, which was attributed to cardiac tamponade caused by pericardial effusion. Urgent pericardiocentesis revealed haemorrhagic fluid, which continued to accumulate after the procedure. A repeat echocardiogram after pericardiocentesis showed dilatation of the right ventricle and severe pulmonary hypertension. Subsequent computed tomography revealed a massive pulmonary embolism in the right lung (Figure) and multiple small emboli in the left lung, while cytological examination of pericardial and pleural fluid showed adenocarcinomatous cells from a primary lung cancer. Pericardial effusion and pulmonary embolism usually present in isolation. Their coexistence in this patient — presumably related to the underlying neoplasm — may paradoxically have saved her life, as the raised right ventricular pressure created by the pulmonary emboli delayed the onset of cardiac tamponade.1 Her condition improved initially with chemotherapy and anticoagulation, but she died a year later due to progression of the lung cancer. PE = pulmonary embolism. PCE = pericardial effusion. PLE = pleural effusion.

Namal Wijesinghe · Cherian Sebastian · Hugh McAlister

Objective: To compare attitudes and practices of Australian medical practitioners, by specialty, to a range of medical decisions at the end of life.Design, setting and participants: As part of an international study, in 2003, a structured questionnaire was mailed to 2964 medical practitioners drawn from membership registers of Australian and Australasian professional colleges. Data from 1478 questionnaires were statistically analysed using validated instruments.Main outcome measures: Practitioners’ willingness to comply with requests from patients and/or their relatives for symptom relief which might also hasten death; provision of terminal sedation and euthanasia, or willingness to provide these on their own initiative.Results: Respondents reported being much more willing to comply with a patient’s request for increasing symptom relief, even at risk of hastening death, than for terminal sedation. Over a quarter of respondents would provide terminal sedation to competent patients on their own initiative. A small number of respondents would intentionally hasten death. There were significant differences by specialty for all three actions. Oncologists, palliative care physicians and geriatricians were least likely to actively hasten death, and more likely to act unilaterally to relieve symptoms as a medical necessity.Conclusions: Perceptions about the causation of death and aspects of medical culture appear to influence physicians’ attitudes towards medical decisions at the end of life. Our findings have implications for medical education, interprofessional communication and discussion between the medical profession and the community.

Malcolm H Parker MLitt, LLM, FACLM · Colleen M Cartwright PhD, MPH, BSocWk(Hons) · Gail M Williams PhD, MSc, MSc(Epidem)

Objective: To investigate current use of Australian snake antivenoms and the frequency and severity of immediate-type hypersensitivity reactions.Design: Nested prospective cohort study as part of the Australian Snakebite Project.Patients and setting: Patients receiving snake antivenom in Australian hospitals between 1 January 2002 and 30 November 2007.Main outcome measures: The use of CSL Limited antivenom; frequency and severity of hypersensitivity reactions to antivenom; premedication and treatment of these reactions.Results: Snake antivenom was administered to 195 patients, mostly for venom-induced consumption coagulopathy (145 patients, 74%), followed by non-specific systemic effects (12%), neurotoxicity (5%) and myotoxicity (4%). Antivenom was given to nine patients (5%) without evidence of envenoming or who were bitten by a species of snake for which antivenom is not required. The commonest antivenoms used were brown snake (46%), tiger snake (30%) and polyvalent (11%). The median dose was four vials (interquartile range, 2–5 vials), and 24 patients received two different types of antivenom. Immediate-type hypersensitivity reactions occurred in 48 patients (25%); 21 satisfied our definition of anaphylaxis, with 11 moderate and 10 severe cases, including nine in which patients were hypotensive. The remaining 27 reactions were mild (skin only). Adrenaline was used in 26 cases with good effect. The frequency of reactions to tiger snake (41%) and polyvalent (41%) antivenoms was higher than that to brown snake antivenom (10%). Hypersensitivity reactions occurred in 11 of 40 patients receiving any form of premedication (28%) and in 2 of 11 given adrenaline for premedication (18%) versus 20 of 86 not receiving premedication (23%).Conclusions: Antivenom was used appropriately, and most commonly for coagulopathy. Hypersensitivity reactions were common, but most were not severe. The discretionary use of premedication was not associated with any reduction in reactions.

Geoffrey K Isbister BSc, FACEM, MD · Simon G Brown MB BS, FACEM, PhD · Ellen MacDonald · Julian White MB BS, MD · Bart J Currie MB BS, FRACP

There is a heavy burden of disease associated with family violence, discrimination, bullying and social exclusion. These important causes of suffering and loss of productivity all relate to a very fundamental feature of human existence and civil(ised) societies — the way we treat each other. We can, and do, make each other sick. Reducing the resultant human and economic costs has major implications for the way we distribute opportunity, wealth and amenity. These, in turn, have implications for the way we protect and empower minority groups, and for legislation, education and the availability of, and access to, services.

Rob Moodie FRACGP, FAFPHM, MPH

Objectives: To review the effectiveness of chronic disease management interventions for physical health problems in the primary care setting, and to identify policy options for implementing successful interventions in Australian primary care.Methods: We conducted a systematic review with qualitative data synthesis, using the Chronic Care Model as a framework for analysis between January 1990 and February 2006. Interventions were classified according to which elements were addressed: community resources, health care organisation, self-management support, delivery system design, decision support and/or clinical information systems. Our major findings were discussed with policymakers and key stakeholders in relation to current and emerging health policy in Australia.Results: The interventions most likely to be effective in the context of Australian primary care were engaging primary care in self-management support through education and training for general practitioners and practice nurses, and including self-management support in care plans linked to multidisciplinary team support. The current Practice Incentives Payment and Service Incentives Payment programs could be improved and simplified to encourage guideline-based chronic disease management, integrating incentives so that individual patients are not managed as if they had a series of separate chronic diseases. The use of chronic disease registers should be extended across a range of chronic illnesses and used to facilitate audit for quality improvement. Training should focus on clear roles and responsibilities of the team members.Conclusion: The Chronic Care Model provides a useful framework for understanding the impact of chronic disease management interventions and highlights the gaps in evidence. Consultation with stakeholders and policymakers is valuable in shaping policy options to support the implementation of the National Chronic Disease Strategy in primary care.

Sarah M Dennis MSc, PhD · Nicholas Zwar FRACGP, PhD · Rhonda Griffiths MSc, PhD · Martin Roland DM, FMedSci · Iqbal Hasan MB BS, MPH · Gawaine Powell Davies MHP · Mark Harris FRACGP, MD

Clinical record A 51-year-old woman of European ancestry presented in 2006 with a 2-month history of lethargy, nausea and arthralgia, and 2 weeks of jaundice. Her past history included gastric bypass surgery for obesity at the age of 40 years, and laminectomy. She had been taking a commercial preparation of black cohosh (20 mg per day) intermittently for 3 years, with titration according to her menopausal symptoms. This preparation was available over the counter. It contained 20 mg of black cohosh root extract per tablet, and the manufacturer recommended a dose of 20 mg twice daily. Two months before symptom onset, the patient increased the dose to the manufacturer’s recommended dose because of worsening menopausal symptoms. The patient was not taking any other medications, including other herbal preparations, paracetamol, or non-steroidal anti-inflammatory drugs. She had no personal or family history of liver disease. She was an ex-smoker, with no history of illicit drug use, significant alcohol consumption, recent travel, tattoos, transfusions or sick contacts. Physical examination revealed jaundice and mild ascites, but no evidence of hepatic encephalopathy or stigmata of chronic liver disease. Results of laboratory studies were consistent with acute hepatitis. Serum albumin concentration was 36 g/L (reference range [RR], 31–44 g/L); elevations were noted in serum concentrations of aspartate aminotransferase (AST) (1327 U/L; RR, < 40 U/L), alanine aminotransferase (ALT) (1230 U/L; RR, < 50 U/L), alkaline phosphatase (ALP) (191 U/L; RR, 30–110 U/L), γ-glutamyltransferase (GGT) (523 U/L; RR, < 40 U/L), and bilirubin (106 μmol/L; RR, < 20 μmol/L). The international normalised ratio (INR) was 1.8 (RR, 1.0–1.2), serum creatinine concentration was 58 μmol/L (RR, 45–90 μmol/L) and MELD (Model for End-Stage Liver Disease) score was 16 (a score > 15 indicates that prognosis at 1 year will be improved by transplantation). Extensive investigations to exclude other causes of acute liver failure gave negative results, including serological tests for hepatitis A, B, and C; cytomegalovirus IgM; Epstein–Barr virus IgG and IgM; antinuclear antibody; anti-liver/kidney microsomal antibodies; antimitochondrial antibody; anti-smooth muscle antibody, α-1 antitrypsin; ceruloplasmin; and fasting iron studies. Abdominal computed tomography 1 month after presentation showed moderate ascites and a shrunken irregular liver contour, with a liver volume of 720 mL. Prominent vessels around the lesser curvature of the stomach suggested portal hypertension with collateral vessel formation. Doppler ultrasound examination a month later confirmed a small liver with coarse heterogeneous echotexture, and a macronodular surface. The portal vein was patent. A liver biopsy 6 weeks after presentation showed massive hepatocellular necrosis with preserved bile ducts, collapsed parenchyma, and no recognisable residual hepatocytes (Figures, A and B). There were extensive mononuclear inflammatory infiltrates with few neutrophils. Perls staining was negative for iron. A diagnosis was made of acute liver injury secondary to black cohosh ingestion. Over the subsequent weeks, the patient’s jaundice worsened, and her serum bilirubin level continued to rise. Frusemide was given to manage developing moderate ascites. Sixty-two days after presentation, the patient developed asterixis (“hepatic flap”), indicating encephalopathy and liver failure. She was diagnosed with subfulminant liver failure suitable for liver transplantation and was listed urgently for transplant. Liver function tests showed a serum albumin concentration of 30 g/L and elevated serum concentrations of AST (202 U/L), ALT (73 U/L), ALP (191 U/L), GGT (64 U/L) and bilirubin (728 μmol/L). The INR was 1.8. Her renal function rapidly deteriorated, with serum creatinine concentration rising to 255 μmol/L. The MELD score reached 37. A liver became available 5 days after the patient was listed, and a successful orthotopic liver transplantation was performed. Her postoperative course was uneventful. The explanted liver weighed 744 g and was distorted by multiple nodules of varying size, from 5 mm to 50 mm (Figure, C). Microscopically, there were areas of extensive submassive necrosis, capsule distortion, collapse of the hepatic parenchyma, and mononuclear inflammatory infiltrates around the portal tracts. Cholestasis was prominent. Nodular regeneration with portal–portal linkage was also evident in some areas, as seen in the pretransplant biopsy. Black cohosh is a herbal remedy used around the world for relief of menopausal symptoms. In Australia, over 200 listed medicines containing black cohosh are available without prescription.1 However, in the past decade, seven case reports of hepatotoxicity associated with black cohosh have been published.1-7 To our knowledge, our patient is the eighth reported case, and the sixth to require liver transplantation. Lessons from practice Black cohosh is a herbal remedy used by millions of women worldwide for the relief of menopausal symptoms. Emerging evidence of severe hepatotoxicity potentially linked with the use of black cohosh has raised concerns regarding its safety profile. The community needs to be educated about potential risks of alternative and herbal medications such as black cohosh, and further regulations are required to monitor the safety of these preparations. Black cohosh (Cimicifuga racemosa, also known as Actaea racemosa) is a perennial plant native to North America. The World Health Organization recognises its use for “treatment of climacteric symptoms such as hot flushes, profuse sweating, sleeping disorders and nervous irritability”.8 The American College of Obstetricians and Gynecologists stated that it may be helpful in the short term (6 months or less) for women with vasomotor symptoms of menopause.9 Although the exact mechanism of action is unknown, the primary active constituent of the black cohosh root is the terpene glycoside fraction, and the rhizome contains biologically active substances, including alkaloids, flavonoids, and tannins. However, despite the growing literature on the efficacy of black cohosh for menopausal symptoms, definite conclusions cannot be drawn because of the methodological shortcomings of available studies, such as lack of blinding, lack of long-term follow-up, and variations in product and dosage.10-12 Two safety reviews have found black cohosh extract to be well tolerated and adverse events to be rare when it is taken for up to 6 months.13,14 However, the seven case reports of hepatotoxicity potentially associated with black cohosh use in the past decade raise concern. Currently, there is no known biologically plausible mechanism to explain this hepatotoxicity, which is likely to be multifactorial. The plant contains both potentially hepatoprotective (triterpene glycosides) and hepatotoxic (salicylates, alkaloids) elements. Extracts and constituents of the rhizome have been shown to induce apoptosis and cell cycle arrest in human breast cancer cells,15,16 while extracts of the related plants Cimicifuga foetida and Cimicifuga dahurica inhibited proliferation of rat and mouse hepatocytes.17 The most likely cause of our patient’s liver failure was her use of black cohosh, although it has been recognised that 10% of patients receiving liver transplantation have idiopathic subfulminant liver failure.18 Our patient’s history of obesity treated with gastric bypass surgery 11 years before is unlikely to have contributed to the liver failure as she had shown no abnormalities of liver function previously, and no features of steatohepatitis were seen in the pretransplant liver biopsy specimens. Our case is also notable as the patient had used black cohosh intermittently at half the manufacturer’s recommended dose for 3 years, and at the manufacturer’s recommended dose (20 mg twice a day) for only 2 months before symptom onset. There is a widespread belief in the community that “natural” plant substances are safe, effective and free of side effects. Various regulatory bodies now recognise the association between black cohosh use and hepatotoxicity, and many recommend warning labels. The Therapeutic Goods Administration (TGA) was the first in the world to announce, in February 2006, that medicines containing black cohosh must include the label: “Warning: black cohosh may harm the liver in some individuals. Use under the supervision of a healthcare professional”.19 In November 2007, the TGA revised the warning to: “In very rare cases, black cohosh has been associated with liver failure. If you experience yellowing of the skin or eyes, dark urine, nausea, vomiting, unusual tiredness, weakness, stomach or abdominal pain, and/or loss of appetite, stop using this product and see your doctor”.20 Randomised controlled trials will provide more definitive information on the safety of black cohosh and its efficacy for alleviating menopausal symptoms. Animal models may provide useful information about the cause of idiosyncratic liver damage. The public needs to be educated about the potential risks of alternative and herbal medications, and further regulations are required to monitor the use and safety of these preparations. Currently, there are no agreed guidelines for monitoring liver function in patients taking black cohosh. We recommend that liver function be checked before and during use of black cohosh.

Elizabeth C-Y Chow MD · Marcus Teo MB BS · John A Ring MB BS, PhD · John W Chen MB BS

Should we be devoting energy and resources to reversing obstructive sleep apnoea in patients without symptoms? Over the past four decades, obstructive sleep apnoea (OSA) has emerged as a prevalent, clinically important disorder. Snoring, which is often a hallmark of OSA, is seemingly ubiquitous in middle-aged men. Over 80% of Australian middle-aged men snore for more than 10% of the night.1 Snoring is also common in women. Although it is undoubtedly an important social nuisance, it remains unclear whether snoring alone (in the absence of sleep apnoea) carries with it any serious health risk. Twenty-five per cent of middle-aged men and 10% of women have OSA, defined as > 5 obstructed breathing events per hour of sleep.2 The prevalence in women rises sharply after menopause. Other risk factors are obesity, older age and a family history of OSA. Population-based studies in China and India indicate that its prevalence is at least as high as that reported in Western countries. A complex interplay between regulation of breathing during sleep, facial anatomy and obesity predicts the development of OSA.2 In contrast to the uncertainty of the effects of simple snoring, OSA clearly has significant health consequences. Many patients with OSA experience excessive daytime sleepiness and impaired cognitive function, increasing the potential for traffic crashes, work accidents and reduced productivity at work.3 Over 50% of Australian truck drivers have mild OSA or worse.4 Moreover, Access Economics has estimated that the cost of sleep disorders to the Australian community is over $7 billion, and much of this cost relates to OSA.5 Increasing awareness of OSA has been followed by an appropriate increase in clinical investigations of sleepy patients with suspected OSA. This is further driven by the availability of cost-effective treatments, notably continuous positive airway pressure (CPAP) and mandibular advancement splints. Recent studies have suggested that OSA is associated with an increased risk of cardiovascular disease.6 Publicity about this research has led to an increasing tendency for people who are not sleepy or who have minimal symptoms to be referred for assessment and treatment of OSA. However, in contrast to the sleepy patient, for whom CPAP usage is reinforced by reduction in sleepiness, asymptomatic patients have more variable compliance.7 Should we be devoting substantial clinical energy and resources to reversing OSA in such patients to prevent cardiovascular disease and death? Certainly, data from cross-sectional and prospective population studies and sleep clinic studies indicate that OSA is associated with a higher prevalence of cardiovascular and cerebrovascular disease and insulin resistance.6 Untreated male patients with severe OSA have significantly greater risks of fatal and non-fatal cardiovascular events than healthy controls (odds ratios, 2.87 and 3.17, respectively).8 However, cross-sectional and observational studies have unmeasured confounders, such as visceral obesity.6 In addition, observational studies can be affected by treatment bias. Patients who refuse to use CPAP and seemingly have higher cardiovascular risk than those who comply with CPAP treatment8 may be the same people who refuse to stop smoking or take lipid-lowering or blood pressure-lowering medication. In contrast, there is good evidence from randomised controlled trials that CPAP lowers blood pressure (mean decrease in systolic and diastolic blood pressure of 2.46 and 1.83 mmHg, respectively), but most studies are relatively short (less than 8 weeks), and treatment effects are hard to demonstrate in patients who are not sleepy.9 The remaining short-term CPAP trials that have focused on other intermediate markers of cardiovascular disease (lipids, glucose control, high-sensitivity C-reactive protein) have been inconclusive. For example, a recent short-term randomised trial failed to show any improvement in insulin sensitivity in patients with type 2 diabetes and OSA.10 No data are available from long-term, well powered, randomised controlled trials assessing the effect of CPAP on hard cardiovascular endpoints, such as myocardial infarction and stroke, in patients with OSA. Medical research is well populated by “positive” results from cross-sectional, observational or short-term intervention studies, but their results have not been reproduced in rigorous, long-term, large-scale clinical trials. To remedy this lack of information, several long-term trials of CPAP treatment in OSA are being planned or have commenced, including one initiated by Australian investigators (Sleep Apnea CardioVascular Endpoints Study [http://www.savetrial.org]). These trials will determine whether treatment of OSA decreases the incidence of new cardiovascular events. In the interim, how should we manage patients with a diagnosis of repetitive OSA who present with complaints of snoring but have minimal or no daytime sleepiness? First, it is important to establish whether such patients are genuinely asymptomatic or simply underreport symptoms that are obvious to their families or work colleagues.11 Second, the disorders of these patients typically are characterised by higher rates of central adiposity, glucose intolerance and other vascular risk factors.6 Given that middle-aged men often neglect to monitor such risk factors, referral for snoring may provide an excellent opportunity for a general health assessment and to institute an intervention, such as advice to exercise and lose weight. Moreover, it would be reasonable to prescribe a trial of CPAP for a patient with asymptomatic OSA and hypertension refractory to maximal medical therapy and to monitor the blood pressure response over 24 hours. Finally, it would be reasonable also to inform asymptomatic patients with severe OSA and coexisting cardiovascular disease of the possible association between OSA and a risk of future vascular events. However, it would be inappropriate to coerce these patients into accepting a treatment that might falsely make them feel secure about future risk and might result in neglect of proven risk factors. Future research, ideally, will enable clinicians to get to the “heart of the matter” when discussing cardiovascular risk management and sleep apnoea with these patients.

Ronald R Grunstein MD, PhD, FRACP · Craig L Phillips BSc

Objectives: To compare results of statistical process-control analyses of in-hospital deaths of patients with acute myocardial infarction by using either administrative or clinical data sources and prediction models, and to assess variation in results according to selected patient characteristics.Design: Retrospective, cross-sectional study comparing variable life-adjusted display (VLAD) curves derived by using administrative or clinical prediction models applied to a single patient sample.Participants and setting: Data from 467 consecutive patients admitted to a tertiary hospital in Queensland, between 1 July 2003 and 31 March 2006, with a coded discharge diagnosis of acute myocardial infarction.Main outcome measure: Statistical estimates of cumulative lives gained or lost in excess of those predicted at the end of the study period.Results: The two prediction models, when applied to all patients, generated almost identical VLAD curves, showing a steadily increasing excess mortality over the study period, culminating in an estimated 11 excess deaths. Risk estimates for individual patients from each model were significantly correlated (r = 0.46, P < 0.001). After exclusion of misclassified cases, out-of-hospital cardiac arrests and deaths within 30 minutes of presentation, replotting the curves reversed the mortality trend and yielded, depending on the model, a net gain of three or seven lives. After further exclusion of transfers in from other hospitals and patients whose care had a palliative or conservative intent, the net gain increased to seven or 10 lives.Conclusion: Appropriate patient selection is more important than choice of dataset or risk-prediction model when statistical process-control methods are used to flag unfavourable mortality trends suggestive of suboptimal hospital care.

Ian A Scott FRACP, MHA, MEd · Peter L Thomson MEngSc, MPH, MBiomedE · Seshasayee Narasimhan MB BS

Objective: To investigate primary health care service utilisation and health presentations among asylum seekers living in Melbourne.Design and setting: Retrospective audit of files of people who attended three Melbourne asylum-seeker health clinics between 1 July 2005 and 30 June 2006.Main outcome measures: Rates of reasons for the encounter, diagnostic tests or investigations required, treatments prescribed and referrals.Results: Data were collected from 998 consultations corresponding to 341 people. Eighty-eight per cent of visits involved people with no Medicare access, owing to their visa status. The most common reasons for the encounter were general and unspecified symptoms or problems (rate, 59.9 per 100 encounters; 95% CI, 55–65), followed by musculoskeletal conditions (27.1; 95% CI, 24–30), and psychological problems (26.5; 95% CI, 23–30). The rate of referrals was 18.3 per 100 encounters (95% CI, 16–21).Conclusions: The three clinics providing services to asylum seekers in Melbourne are delivering care to a considerable number of people with complex health needs. A substantial number of asylum seekers present to clinics with psychological and social problems. Most cannot access government-subsidised health care. This must be addressed urgently by policy change at the federal and state and territory levels.

Ignacio Correa-Velez MB BS, PhD · Vanessa Johnston MB BS, MPH · Joanne Kirk RN · Angeline Ferdinand BA

We report the case of a 59-year-old severely obese man with coexisting type 2 diabetes, hypertension and dyslipidaemia who was treated with a very-low-calorie diet (VLCD) program for 12 months. He continued to lose weight during the treatment, with marked improvement in his comorbidities and no adverse effects. This case demonstrates that prolonged use of a VLCD under close medical supervision is safe and effective in certain obese patients. Clinical recordA 59-year-old severely obese man was admitted to hospital with a 3-day history of gradually progressive paraesthesia and mild weakness affecting all four limbs, with a background of polydipsia, polyuria and fatigue over the previous 4 months. On examination, his weight was 169.5 kg and his height was 1.90 m (body mass index [BMI], 47.0 kg/m2). He was hypertensive (167/80 mmHg) and afebrile. He had mild weakness in a pyramidal pattern in the legs. Upper and lower limb reflexes were brisk, ankle jerks were absent, plantar responses were upgoing bilaterally, and sensation was reduced in a stocking distribution. The cranial nerves and speech were unaffected and visual fields were normal. Cardiovascular, respiratory and abdominal examinations were unremarkable. The presence of acanthosis nigricans and a fungal toenail infection were noted. Initial laboratory investigations revealed a random blood glucose level of 22.2 mmol/L (reference range, 3.3–5.5 mmol/L) and a glycated haemoglobin (HbA1c) level of 12.2% (reference range, 4.3%–6.0%). Urinary ketones were not detected. Levels of electrolytes, inflammatory markers and vitamin B12 were normal. Liver function tests showed a mild generalised elevation, and lipid levels were raised (Box 1). An electrocardiogram (ECG), non-contrast computed tomography brain scan, lumbar puncture and carotid Doppler ultrasound were normal. Nerve conduction studies showed an axonal sensorimotor neuropathy, with the lower limbs more severely affected than the upper limbs. Neurological findings remained stable during the hospital stay, and a provisional diagnosis of a cervical myelopathy with peripheral neuropathy was made. Magnetic resonance imaging of the spine could not be performed because of the patient’s large size. The patient was treated with aspirin 100 mg daily, simvastatin 20 mg daily and metformin 500 mg twice daily. On the day of discharge (Day 6), he commenced a very-low-calorie diet (VLCD) (Optifast VLCD, Novartis Consumer Health Australasia, Melbourne, Vic) three times daily. Blood glucose readings at discharge were 6–8 mmol/L. After discharge, he commenced a daily exercise program. Over the following 12 months, the patient attended the weight control clinic at our hospital. He continued on an intensive regimen of Optifast VLCD three times a day for 5 months, and then began a transition phase (two Optifast VLCD meals plus one low-fat meal per day). Over the 12 months, the patient’s weight fell steadily (Box 2, Box 3). At 1-year follow-up, he had lost 43% of his initial weight and was down to 96.5 kg (BMI, 26.7 kg/m2). He was normotensive (125/80 mmHg), and his fasting blood glucose and HbA1c levels were in the non-diabetic range. Full blood examination, electrocardiographic readings, and levels of electrolytes, calcium, magnesium, folate, vitamin B12, vitamin D and uric acid were normal. Liver function tests had normalised, and the lipid profile had improved significantly (Box 1). Bone mineral density (measured by dual energy x-ray absorptiometry) was normal at 6 and 12 months after commencement of the VLCD. Neurological symptoms improved, with persistence of limb weakness and sensory loss. Planned management was to gradually reduce the Optifast diet and enter a supervised weight maintenance phase, which would include an education program about lifestyle changes, frequent clinic visits and close observation of weight. DiscussionVLCDs involve replacement of meals with foods or formulas providing 1675–3350 kJ/day. They are commonly used in medically supervised weight reduction programs for patients with BMI > 30 kg/m2 (or > 27 kg/m2 with obesity-related comorbidities), or for whom rapid weight loss is necessary. Several formulations are available without prescription (Box 4). VLCDs should provide at least 0.8 g protein per kilogram of ideal bodyweight per day (to preserve lean body mass1), along with the recommended daily allowances of minerals, vitamins, trace elements and essential fatty acids. Around 10 g/day fat is recommended to stimulate gallbladder contraction.2 Although optimal caloric and carbohydrate intakes are unknown, 50 g carbohydrate daily has been suggested as a suitable quantity to maintain normoglycaemia and to prevent loss of electrolytes and protein.2 There is no advantage in reducing energy intake below 3350 kJ/day.3 Treatment duration varies but is usually 8–16 weeks.1 To our knowledge, our report is the first to document the use of a VLCD for 12 months. There is concern about the safety of VLCDs, most of which stems from the occurrence of over 60 deaths associated with a popular liquid protein diet, available in the 1970s, that consisted entirely of solutions of collagen or gelatine hydrolysates.4 Many of the deaths occurred in people with pre-existing comorbidities.4 However, 17 deaths (16 in women) occurred in relatively young (median age, 35 years) and otherwise reasonably healthy people. These 17 people, who were severely obese (mean BMI, 40.6 kg/m2), remained on the diet for an average of 5 months and lost a large amount of weight (mean, 35%). Postmortem findings were consistent with the cardiac effects of protein-calorie malnutrition (which include myocardial atrophy, QT prolongation and ventricular arrhythmias).5 In contrast, VLCDs in current use contain high-quality protein and appear to be safe.1 In 1998, Rössner described the case of a patient who had lived solely on a VLCD preparation for 46 weeks without medical supervision, in whom no adverse events occurred other than cholelithiasis and one episode of palpitations, after which ECG monitoring over a 24-hour period showed no abnormality.6 Common minor adverse effects associated with VLCDs, which include cold intolerance, dry skin, hair loss, constipation, headaches, fatigue and dizziness, are generally self-limiting and transient. Other potential effects are gallstones, increased serum uric acid levels, precipitation of gout and reduced bone mineral density. When beginning a VLCD, liver function tests, lipid profile measurements, a full blood count and iron studies should be carried out, and levels of electrolytes, creatinine and uric acid should be measured. Testing of electrolyte and creatinine levels should be repeated about 6 weeks after commencement, or earlier if more careful monitoring is required (eg, in patients who have renal impairment or are using diuretics). If the VLCD is to continue for more than 12 weeks, it is advisable to repeat the baseline tests at least every 2 months.7 Obese people typically achieve a mean weight loss of 1.5–2.5 kg per week using a VLCD. A 2001 meta-analysis concluded that, after using a VLCD, subjects maintained a significantly greater weight loss at 4.5 years (mean loss, 6.6% of initial weight) than after a hypocaloric balanced diet (mean loss, 2.1% of initial weight).8 Taking meal replacements once or twice daily in conjunction with a reduced-calorie diet is also effective for long-term weight maintenance.9 Advantages of VLCDs include the motivating effect of rapid weight loss, the convenience of meal replacement (which improves adherence compared with an ad-libitum low-fat diet)10 and a mild ketosis, which may suppress hunger.7 VLCDs also help with several obesity-related comorbidities by reducing levels of total cholesterol, low-density lipoprotein, triglycerides and blood glucose and by reducing blood pressure, insulin resistance1 and hepatic steatosis.11 All of these benefits were obtained by our patient. To date, bariatric surgery has been the most effective long-term treatment option for obesity. The Swedish Obese Subjects Study, a large prospective controlled study of severely obese patients, found significantly greater weight loss in the surgically treated group than the control group (23.4% bodyweight lost [surgical group] v 0.1% gained [control group] at 2 years, and 16.1% lost [surgical group] v 1.6% gained [control group] at 10 years).12 Similar weight reductions after surgery were reported in a study of mildly to moderately obese subjects13 and in a meta-analysis of bariatric surgery trials.14 Pharmacotherapy for weight loss has only modest benefits, with loss of around 3%–5% bodyweight over 1–4 years reported in a recent meta-analysis.15 The 43% weight loss achieved by our patient at 12 months is comparable with results reported for surgery. Weight maintenance will be his next major challenge. Increasing evidence indicates that physiological changes occur after diet-induced weight loss, including decreased levels of leptin, glucose, insulin, free fatty acids, cholecystokinin and triiodothyronine (T3), and increased levels of reverse T3 and ghrelin. Many of these changes would be expected to reduce satiety and increase hunger, possibly contributing to the weight regain frequently seen after weight loss. Our patient may continue to replace one meal a day with Optifast in the longer term to assist with weight maintenance. As there is growing evidence of physiological adaptations after weight loss that encourage weight regain, pharmacotherapy will be introduced if lifestyle changes prove insufficient to maintain his current weight. Bariatric surgery could also be considered if his weight loss cannot be maintained. Our report shows that, under close medical supervision in certain obese patients, a VLCD may be used safely and effectively for a period of at least 12 months. Prevention of weight regain remains difficult. 1 Blood biochemistry measurements Biochemical levels At baseline At 6 months At 12 months Reference range Total cholesterol (mmol/L) 7.9 3.9 4.8 < 5.5 Triglycerides (mmol/L) 2.4 1.6 0.5 < 2.0 High-density lipoprotein (mmol/L) 1.0 0.8 1.4 > 1.0 Low-density lipoprotein (mmol/L) 5.8 2.4 3.2 < 2.5 Fasting glucose (mmol/L) 16.5 4.5 4.5 3.3–5.5 Glycated haemoglobin (%) 12.2 4.8 4.7 4.3–6.0 Potassium (mmol/L) 4.1 3.9 4.0 3.5–5.0 Creatinine (μmol/L) 107 85 89 30–110 Albumin (g/L) 34 39 40 36–48 Bilirubin (μmol/L) 31 22 20 < 18 Alkaline phosphatase (U/L) 100 70 68 32–91 Alanine aminotransferase (U/L) 88 23 22 < 45 γ-Glutamyltransferase (U/L) 113 21 27 < 55 2 Patient’s weight loss during maintenance of a very-low-calorie diet over a 12-month period 3 Patient at baseline and after 12 months on a very-low-calorie diet 4 Comparison of available very-low-calorie diet (VLCD) formulations* Product† Energy (kJ) Carbohydrate (g) Protein (g) Fat (g) Optifast VLCD‡ 1908 45.0 51.9 6.9 OptiSlim 2000§ 1958 48.1 48.4 4.7 KicStart¶ 2636 58.2 74.7 8.4 * Values given are per 3 × 40 g sachets of chocolate shake prepared as directed. Figures in the table are daily amounts, but do not take into account the additional vegetables recommended along with the VLCD. † All three products are available without prescription. ‡ Novartis Consumer Health Australasia, Melbourne, Vic. § OptiPharm, Melbourne, Vic. ¶ Pharmacy Health Solutions, Sydney, NSW.

Priya Sumithran MB BS, FRACP · Joseph Proietto MB BS, FRACP, PhD